Clinical Assistant Professor, Anesthesiology, Perioperative and Pain Medicine
Fellowship: Stanford University Pain Management Fellowship (2014) CA
Medical Education: University of Colorado School of Medicine (2008) CO
Internship: University of Colorado General Surgery Residency (2009) CO
MSc, Stanford University, Epidemiology and Clinical Research (2017)
Board Certification: American Board of Anesthesiology, Pain Medicine (2014)
Board Certification: American Board of Anesthesiology, Anesthesiology (2013)
Residency: University Of Virginia Health System (2012) VA
A Study of M207 With Intranasal Zolmitriptan in Healthy Volunteers
This is a single-center, open-label, randomized, four-way crossover study. Each subject will receive each of the four study treatments once, followed by in-clinic monitoring and extensive blood sample collection for pharmacokinetic analysis. Dosing will occur approximately 48 hours apart, until completion of dosing in randomized order per the treatment sequence tables. Plasma samples from the dosing days will be sent to the analytical laboratory for analysis and tolerability for each of the dose levels will be summarized. After completion of the four dosing days, subjects will be assessed one final time and dismissed from the study.
Stanford is currently not accepting patients for this trial.
A Study to Evaluate the Long-Term Safety of M207 in the Acute Treatment of Migraine
This is an open-label, twelve-month safety study. There is a screening period followed by a run-in period to record migraine activity. Qualified subjects will receive study medication for up to twelve months for the treatment of multiple migraine attacks. Using the electronic diary (eDiary) to confirm they are experiencing a qualified migraine, subjects will self-administer the patches and respond to questions in the eDiary post treatment administration.
Stanford is currently not accepting patients for this trial.
Open Label Crossover Study Pharmacokinetics (PK) Study in Healthy Volunteers Receiving Various Forms of Fentanyl
A partially randomized, open-label, 3-way crossover, single-center, systemic and CSF PK and bioavailability study in healthy volunteers.
Stanford is currently not accepting patients for this trial.
Pharmacokinetics & Safety of Cambia® in Migraine With or Without Aura in 12-17 Year Olds
Study Objectives: 1. The primary objective is to characterize the pharmacokinetics of a single oral administration of 50 mg Cambia in pediatric subjects, ages 12-17 years with a diagnosis of episodic migraine with or without aura. 2. The secondary objectives are to determine: 1. The safety and tolerability of Cambia from a single dose 2. Three-month safety evaluation of Cambia in outpatient usage in this population
Stanford is currently not accepting patients for this trial.
Simulated Driving Performance, Daytime Sedation and Cognition in Healthy Volunteers Taking Gralise, Neurontin or Lyrica
Phase 4, double-blind, placebo-controlled, four treatment, four sequence crossover study comparing simulated driving performance, daytime sedation and cognition in healthy volunteers administered therapeutic doses of Gralise® (Treatment A), Neurontin® (Treatment B), Lyrica® (Treatment C) and placebo (Treatment D). All doses were administered under fed conditions.
Stanford is currently not accepting patients for this trial.
Stanford Accelerated Recovery Trial (START)
The goal of this study is to determine whether administering Gabapentin prior to surgery affects duration of pain and opioid use post-surgery. The investigators aim to compare gabapentin to placebo in a prospective, randomized clinical trial in which patients will be followed post-surgery until pain resolves and opioid use ceases.
Stanford is currently not accepting patients for this trial. For more information, please contact Debra Clay, 650-724-1753.
- Effect of Perioperative Gabapentin on Postoperative Pain Resolution and Opioid Cessation in a Mixed Surgical Cohort: A Randomized Clinical Trial (vol 153, pg 303, 2018) JAMA SURGERY 2022; 157 (6): 553
- Effect of Perioperative Gabapentin on Postoperative Pain Resolution and Opioid Cessation in a Mixed Surgical Cohort: A Randomized Clinical Trial (vol 153, pg 303, 2018) JAMA SURGERY 2022
Long term safety, tolerability, and efficacy of intracutaneous zolmitriptan (M207) in the acute treatment of migraine.
The journal of headache and pain
2021; 22 (1): 37
OBJECTIVE: To determine the long-term safety and tolerability profile of M207 in the acute treatment of migraine.BACKGROUND: M207 is an investigational microneedle-based system for intracutaneous delivery of zolmitriptan for the treatment of migraine attacks. Following on the positive results of a Phase 2/3 placebo-controlled efficacy study (ZOTRIP), this study was designed to evaluate the safety of this novel product during repeated use for the treatment of migraine attacks.METHODS: In this 6-12month open-label, multicenter observational study, participants used an eDiary to record headache symptoms and adverse events at specified intervals up to 48h following treatment of a qualifying attack with M207 3.8mg (intracutaneous zolmitriptan). Participants underwent clinical evaluations at specified intervals up to 12months.RESULTS: Among 335 participants who treated ≥1 migraine attack, 257 completed 6months and 127 completed 1year of treatment. The most common reason for withdrawal from the study was a low frequency of reported attacks post randomization. Overall, 5963 migraine attacks were treated. Most participants (96%) experienced at least 1 adverse event, the vast majority of which concerned the application site, and>95% of which were mild. Fifteen participants (4%) withdrew due to adverse events; 4 withdrew due to 7 application site reactions, 6 of which were mild. Participants achieved pain freedom in 2477/5617 (44%) of attacks, most bothersome symptom freedom in 3315/5330 (62%) of attacks, and pain relief 2h post-dose in 4552/5617 (81%) of attacks. Sustained pain freedom 2-24h was seen in 1761/4698 (38%) of attacks, and 2-48h in 1534/4429 (35%) of attacks.CONCLUSIONS: The majority of participants experienced cutaneous adverse reactions such as application site erythema, swelling, and bleeding, and most reactions were scored as mild. These results are consistent with what was observed in the single migraine attack treatment ZOTRIP trial indicating that M207 is well tolerated in the setting of longer-term repeated use. Efficacy findings were also similar to those in the ZOTRIP trial.TRIAL REGISTRATION: Clinicaltrials.gov on September 13, 2017 ( NCT03282227 ).
View details for DOI 10.1186/s10194-021-01249-z
View details for PubMedID 34001002
Building regional anesthesia capacity in limited-resource settings: a pilot study evaluating a 4-week curriculum
2021; 11 (1): 29–37
Aim: To pilot a 4-week regional anesthesia curriculum for limited-resource settings. Intervention: A baseline needs assessment and knowledge test were deployed. The curriculum included lectures and hands-on teaching, followed by knowledge attainment tests. Results: Scores on the knowledge test improved from a mean of 37.1% (SD 14.7%) to 50.9% (SD 18.6%) (p = 0.017) at 4 weeks and 49% at 24 months. An average of 1.7 extremity blocks per month was performed in 3 months prior to the curriculum, compared with an average of 4.1 per month in 8 months following. Conclusion: This collaborative curriculum appeared to have a positive impact on the knowledge and utilization of regional anesthesia.
View details for DOI 10.2217/pmt-2020-0044
View details for Web of Science ID 000579459700001
View details for PubMedID 33073715
Erector Spinae Regional Anesthesia for Robotic Coronary Artery Bypass Surgery Is Not Associated With Reduced Postoperative Opioid Use: A Retrospective Observational Study.
Journal of cardiothoracic and vascular anesthesia
OBJECTIVE: Regional anesthesia techniques are gaining traction in cardiac surgery. The aim of this study was to compare the analgesic efficacy of erector spinae plane block catheters (ESPBC), serratus anterior plane block catheters (SAPBC), and paravertebral single-shot block (PVB) versus no block after robotic minimally invasive direct coronary artery bypass (MIDCAB).DESIGN: This was a retrospective observational study of routinely recorded data.SETTING: The study was performed at a single healthcare system.PARTICIPANTS: All patients underwent robotic MIDCAB.INTERVENTION: Data were analyzed from 346 patients during a 53-month period. The clinical data warehouse was queried for all robotic MIDCAB surgeries. Variables abstracted included type of nerve block, age, sex, use of adjuncts, Society of Thoracic Surgeons predicted short length of stay (PSLOS), total opioid consumption during the 72 hours after surgery, and postoperative hospital length of stay (LOS). The primary outcome was total oral morphine milligram equivalents (MME) consumed during the first 72 hours after surgery. The secondary outcome was hospital LOS.MEASUREMENTS AND MAIN RESULTS: In a model adjusting for PSLOS, the authors did not observe an association between ESPBC and the reduction of total administered oral MME within 72 hours after surgery. There was no significant difference in MME when comparing patients who received PVB to patients with ESPBC. Older age and female sex were associated with significantly lower MME. Patients who received ESPBC had a significantly shorter hospital LOS than patients with SAPBC.CONCLUSIONS: These findings suggested that postoperative pain after MIDCAB surgery might not be completely covered by ESPBC. Prospective studies are needed to further elucidate the value of this technique for robotic MIDCAB.
View details for DOI 10.1053/j.jvca.2020.09.112
View details for PubMedID 33127286
Preoperative Factors Associated with Remote Postoperative Pain Resolution and Opioid Cessation in a Mixed Surgical Cohort: Post Hoc Analysis of a Perioperative Gabapentin Trial.
Journal of pain research
2020; 13: 2959–70
Preoperative patient-specific risk factors may elucidate the mechanisms leading to the persistence of pain and opioid use after surgery. This study aimed to determine whether similar or discordant preoperative factors were associated with the duration of postoperative pain and opioid use.In this post hoc analysis of a randomized, double-blind, placebo-controlled trial of perioperative gabapentin vs active placebo, 410 patients aged 18-75 years, undergoing diverse operations underwent preoperative assessments of pain, opioid use, substance use, and psychosocial variables. After surgery, a modified Brief Pain Inventory was administered over the phone daily up to 3 months, weekly up to 6 months, and monthly up to 2 years after surgery. Pain and opioid cessation were defined as the first of 5 consecutive days of 0 out of 10 pain or no opioid use, respectively.Overall, 36.1%, 19.8%, and 9.5% of patients continued to report pain, and 9.5%, 2.4%, and 1.7% reported continued opioid use at 3, 6, and 12 months after surgery. Preoperative pain at the future surgical site (every 1-point increase in the Numeric Pain Rating Scale; HR 0.93; 95% CI 0.87-1.00; P=0.034), trait anxiety (every 10-point increase in the Trait Anxiety Inventory; HR 0.79; 95% CI 0.68-0.92; P=0.002), and a history of delayed recovery after injury (HR 0.62; 95% CI 0.40-0.96; P=0.034) were associated with delayed pain cessation. Preoperative opioid use (HR 0.60; 95% CI 0.39-0.92; P=0.020), elevated depressive symptoms (every 5-point increase in the Beck Depression Inventory-II score; HR 0.88; 95% CI 0.80-0.98; P=0.017), and preoperative pain outside of the surgical site (HR 0.94; 95% CI 0.89-1.00; P=0.046) were associated with delayed opioid cessation, while perioperative gabapentin promoted opioid cessation (HR 1.37; 95% CI 1.06-1.77; P=0.016).Separate risk factors for prolonged post-surgical pain and opioid use indicate that preoperative risk stratification for each outcome may identify patients needing personalized care to augment universal protocols for perioperative pain management and conservative opioid prescribing to improve long-term outcomes.
View details for DOI 10.2147/JPR.S269370
View details for PubMedID 33239904
View details for PubMedCentralID PMC7680674
Efficacy of Qtrypta (zolmitriptan intracutaneous system) Before and After the Initiation of CGRP Antibody Therapy in Subjects with Migraine - a Preliminary Assessment
SAGE PUBLICATIONS LTD. 2019: 394
View details for Web of Science ID 000491167100061
- Review of Acute Treatment of Migraine Trial Results With the New FDA Endpoints: Design Implications for Future Trials HEADACHE 2019; 59 (5): 819–24
Review of Acute Treatment of Migraine Trial Results With the New FDA Endpoints: Design Implications for Future Trials.
BACKGROUND: In October 2014, the US Food and Drug Administration released a draft guidance for the development of drugs for the acute treatment of migraine. This guidance offered the option of replacing the previously required 4 co-primary endpoints: pain freedom, freedom from nausea, freedom from photophobia, and freedom from phonophobia, all at 2 hours posttreatment, with 2 co-primary endpoints: pain freedom and freedom from most bothersome symptom (MBS) other than pain, both at 2 hours posttreatment. At the time the new draft guidance was released, no large clinical trials had been undertaken with these 2 co-primary endpoints, posing a challenge in determining the sample size that might be required to achieve statistical significance. As a number of trials have now been completed, we conducted a review of the observed placebo responses, drug effect sizes, and sample sizes to better inform the design of future trials.METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane library for primary publications of phase 3 randomized, placebo-controlled, double-blind acute migraine treatment trials that used pain freedom and MBS freedom as primary or planned secondary endpoints. For each endpoint, placebo response rates were determined and used to generate estimates of sample size, assuming differences between placebo and active treatment groups of 10%, 15%, and 20%. Sample size calculations were based on 80% power using a 2-group continuity corrected chi-square test with a 5% 2-sided significance level.RESULTS: We identified abstracts or full-length papers describing results of 8 clinical trials employing the new co-primary endpoints. The mean placebo response rate for 2-hour pain freedom was 16.75% (range 11.8-21.3%) and treatment effect (difference in response rates between active and placebo groups) ranged from 5.0% to 27.2%. For 2-hour MBS freedom, the mean placebo response rate was 32.8% (range 25.2-48.1%), and the range of treatment effect was 8.9% to 25.4%. Based on a placebo response rate of 17% for pain freedom, the sample sizes that would have been required to achieve statistical significance were n=269, n=128, and n=77, for treatment effect sizes of 10%, 15%, and 20%, respectively. For MBS, assuming a placebo response rate of 33%, the corresponding required sample sizes would have been n=389, n=181, and n=105.CONCLUSIONS: The observed range of placebo response and treatment effect sizes suggests that use of the newly recommended 2 co-primary endpoints could reduce the sample sizes required to achieve significance compared with past trials using 4 primary endpoints (in which mean and median group sizes for recent trials were 375 and 362, respectively). However, the initial trials using the newly recommended co-primary endpoints tended to treat more participants than would have been minimally required. We anticipate that with the growing body of information regarding the use of these new endpoints, samples sizes may be more aligned with treatment efficacy, enabling faster and more cost-effective trials for acute migraine treatment.
View details for PubMedID 30953576
- Factors Associated With Acute Pain Estimation, Postoperative Pain Resolution, Opioid Cessation, and Recovery Secondary Analysis of a Randomized Clinical Trial JAMA NETWORK OPEN 2019; 2 (3)
Factors Associated With Acute Pain Estimation, Postoperative Pain Resolution, Opioid Cessation, and Recovery: Secondary Analysis of a Randomized Clinical Trial.
JAMA network open
2019; 2 (3): e190168
Importance: Acute postoperative pain is associated with the development of persistent postsurgical pain, but it is unclear which aspect is most estimable.Objective: To identify patient clusters based on acute pain trajectories, preoperative psychosocial characteristics associated with the high-risk cluster, and the best acute pain predictor of remote outcomes.Design, Setting, and Participants: A secondary analysis of the Stanford Accelerated Recovery Trial randomized, double-blind clinical trial was conducted at a single-center, tertiary, referral teaching hospital. A total of 422 participants scheduled for thoracotomy, video-assisted thoracoscopic surgery, total hip replacement, total knee replacement, mastectomy, breast lumpectomy, hand surgery, carpal tunnel surgery, knee arthroscopy, shoulder arthroplasty, or shoulder arthroscopy were enrolled between May 25, 2010, and July 25, 2014. Data analysis was performed from January 1 to August 1, 2018.Interventions: Patients were randomized to receive gabapentin (1200 mg, preoperatively, and 600 mg, 3 times a day postoperatively) or active placebo (lorazepam, 0.5 mg preoperatively, inactive placebo postoperatively) for 72 hours.Main Outcomes and Measures: A modified Brief Pain Inventory prospectively captured 3 surgical site pain outcomes: average pain and worst pain intensity over the past 24 hours, and current pain intensity. Within each category, acute pain trajectories (first 10 postoperative pain scores) were compared using a k-means clustering algorithm. Fifteen descriptors of acute pain were compared as predictors of remote postoperative pain resolution, opioid cessation, and full recovery.Results: Of the 422 patients enrolled, 371 patients (≤10% missing pain scores) were included in the analysis. Of these, 146 (39.4%) were men; mean (SD) age was 56.67 (11.70) years. Two clusters were identified within each trajectory category. The high pain cluster of the average pain trajectory significantly predicted prolonged pain (hazard ratio [HR], 0.63; 95% CI, 0.50-0.80; P<.001) and delayed opioid cessation (HR, 0.52; 95% CI, 0.41-0.67; P<.001) but was not a predictor of time to recovery in Cox proportional hazards regression (HR, 0.89; 95% CI, 0.69-1.14; P=.89). Preoperative risk factors for categorization to the high average pain cluster included female sex (adjusted relative risk [ARR], 1.36; 95% CI, 1.08-1.70; P=.008), elevated preoperative pain (ARR, 1.11; 95% CI, 1.07-1.15; P<.001), a history of alcohol or drug abuse treatment (ARR,1.90; 95% CI, 1.42-2.53; P<.001), and receiving active placebo (ARR, 1.27; 95% CI, 1.03-1.56; P=.03). Worst pain reported on postoperative day 10 was the best predictor of time to pain resolution (HR, 0.83; 95% CI, 0.78-0.87; P<.001), opioid cessation (HR, 0.84; 95% CI, 0.80-0.89; P<.001), and complete surgical recovery (HR, 0.91; 95% CI, 0.86-0.96; P<.001).Conclusions and Relevance: This study has shown a possible uniform predictor of remote postoperative pain, opioid use, and recovery that can be easily assessed. Future work is needed to replicate these findings.Trial Registration: ClinicalTrials.gov Identifier: NCT01067144.
View details for PubMedID 30821824
Efficacy of ADAM Zolmitriptan for the Acute Treatment of Difficult-to-Treat Migraine Headaches.
To understand the efficacy of zolmitriptan applied with Adhesive Dermally Applied Microarray (ADAM) in treating types of migraine (those with severe headache pain, the presence of nausea, treatment ≥2 hours after migraine onset, or migraine present upon awakening) that are historically considered to be less responsive to oral medications.ADAM is an investigational system for intracutaneous drug administration. In a pivotal Phase 2b/3 study (ZOTRIP, N = 321 in the modified intention-to-treat population), ADAM zolmitriptan 3.8 mg provided superior pain freedom and freedom from patients' usual most bothersome associated symptom (MBS), compared with placebo at 2 hours post-dose. We undertook a post hoc analysis of data from the ZOTRIP trial to examine these same outcomes in subsets of patients whose migraine characteristics have been associated with poorer outcomes when treated with oral medications.The ZOTRIP trial was a multicenter, randomized, double-blind, placebo-controlled, parallel group Phase 2b/3 study conducted at 36 sites in the United States. Presented here are post hoc subgroup analyses of patients with nausea (n = 110) or severe pain (n = 72) at baseline, those whose treatment was delayed 2 or more hours after onset (n = 75), and those who awoke with migraine (n = 80). The Cochran-Mantel-Haenszel test was used to assess whether patients in the ADAM zolmitriptan 3.8 mg group had superior treatment outcomes compared with placebo.In patients with nausea, 2-hour pain freedom was achieved in 44% (26/59) in the ADAM zolmitriptan 3.8 mg group and 14% (7/51) in the placebo group (P = .005) (odds ratio = 5.11, 95% CI: 1.96-13.30), and 2-hour MBS freedom was achieved in 68% (40/59) in the active treatment group and 45% (23/51) of those receiving placebo (P = .009) (odds ratio = 2.86, 95% CI: 1.28-6.43). For those with severe pain, corresponding pain-free values were 26% (10/39) and 15% (5/33) (P = .249) (odds ratio = 2.14, 95% CI: 0.60-7.62), and MBS-free values were 64% (25/39) and 42% (14/33) (P = .038) (odds ratio = 2.86, 95% CI: 1.05-7.79). Among participants who awoke with migraine, 44% (16/36) and 16% (7/44) were pain-free in the ADAM zolmitriptan 3.8 mg and placebo groups, respectively (P = .006) (odds ratio = 4.29, 95% CI: 1.50-12.31), and 72% (26/36) vs 39% (17/44) were MBS-free, respectively (P = .003) (odds ratio = 4.40, 95% CI: 1.61-12.05). In those whose treatment was delayed ≥2 hours, pain freedom in the active treatment group and placebo group were 33% (12/36) and 10% (4/39), respectively (P = .017) (odds ratio = 4.33, 95% CI: 1.24-15.10), and MBS freedom was achieved in 69% (25/36) and 41% (16/39), respectively, in the delayed treatment group (P = .014) (odds ratio = 3.37, 95% CI: 1.27-8.95). No significant effects (overall interaction P = .353) were observed in logistical regression models of treatment by subgroup interaction.Severe pain, delayed treatment, awakening with a headache, and the presence of nausea are factors that predict a poorer response to acute migraine treatment. In these post hoc analyses of subgroups of patients with each of these characteristics in the ZOTRIP trial, participants receiving ADAM zolmitriptan 3.8 mg displayed nearly uniformly better headache responses (2-hour headache freedom and 2-hour MBS freedom) compared with those who received placebo.
View details for DOI 10.1111/head.13482
View details for PubMedID 30698272
Use of Most Bothersome Symptom as a Coprimary Endpoint in Migraine Clinical Trials: A Post-Hoc Analysis of the Pivotal ZOTRIP Randomized, Controlled Trial
2018; 58 (7): 986–92
To better understand the utility of using pain freedom and most bothersome headache-associated symptom (MBS) freedom as co-primary endpoints in clinical trials of acute migraine interventions.Adhesive dermally applied microarray (ADAM) is an investigational system for intracutaneous drug administration. The recently completed pivotal Phase 2b/3 study (ZOTRIP), evaluating ADAM zolmitriptan for the treatment of acute moderate to severe migraine, was one of the first large studies to incorporate MBS freedom and pain freedom as co-primary endpoints per recently issued guidance by the US Food and Drug Administration. In this trial, the proportion of patients treated with ADAM zolmitriptan 3.8 mg, who were pain-free and MBS-free at 2 hours post-dose, was significantly higher than for placebo.We undertook a post-hoc analysis of data from the ZOTRIP trial to examine how the outcomes from this trial compare to what might have been achieved using the conventional co-primary endpoints of pain relief, nausea, photophobia, and phonophobia.Of the 159 patients treated with ADAM zolmitriptan 3.8 mg or placebo, prospectively designated MBS were photophobia (n = 79), phonophobia (n = 43), and nausea (n = 37). Two-hour pain free rates in those with photophobia as the MBS were 36% for ADAM zolmitriptan 3.8 mg and 14% for placebo (P = .02). Corresponding rates for those with phonophobia as the MBS were 14% and 41% (P = .05). For those whose MBS was nausea, corresponding values were 56% and 16%, respectively (P = .01). Two-hour freedom from the MBS for active drug vs placebo were 67% vs 35% (P < .01) for photophobia, 55% vs 43% (P = .45) for phonophobia, and 89% vs 58% for nausea (P = .04). MBS freedom but not pain freedom was achieved in 28%. Only 1 patient (1%) achieved pain freedom, but not MBS freedom. The proportion with both pain and MBS freedom was highest (56%) among those whose MBS was nausea.In this study, the use of MBS was feasible and seemed to compare favorably to the previously required 4 co-primary endpoints.
View details for DOI 10.1111/head.13327
View details for Web of Science ID 000442734800008
View details for PubMedID 29782049
View details for PubMedCentralID PMC6174959
Effects of gabapentin, pregabalin and gastroretentive gabapentin on simulated driving, daytime sedation and cognition
2018; 8 (4): 297–306
Randomized Phase I study examining the effects of gabapentinoids gabapentin, pregabalin and gastroretentive gabapentin on simulated driving performance, sedation and cognitive function in healthy volunteers (n = 32).Driving attentiveness, sleepiness and cognition were evaluated prior to subjects receiving study doses. Blood samples were collected during each treatment.Subjects receiving gastroretentive gabapentin showed less change in variation in lateral lane position (p = 0.0275), less tremor (p = 0.0304) and fewer vision disturbances compared with gabapentin (p = 0.0177). Statistically significant decrease in One Card Learning Test performance was observed after treatment with gastroretentive gabapentin.Gastroretentive gabapentin demonstrated reduced driving impairment and lower scores on key neurotoxicity measures. Further studies in patients with postherpetic neuralgia are needed. Clinical trial number: NCT03179345.
View details for DOI 10.2217/pmt-2018-0005
View details for Web of Science ID 000435507400009
View details for PubMedID 29671676
Randomized, double-blind, placebo-controlled, parallel-group, multi-center study of the safety and efficacy of ADAM zolmitriptan for the acute treatment of migraine
2018; 38 (2): 215–24
Objective To determine the efficacy, tolerability, and safety of ascending doses of Adhesive Dermally-Applied Microarray (ADAM) zolmitriptan versus placebo for acute migraine treatment. Background ADAM is a novel patient-administered system for intracutaneous drug administration. In a phase 1 pharmacokinetic study, zolmitriptan administered using ADAM had much faster absorption than oral administration with higher exposure in the first two hours. Methods This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase 2b/3 study evaluating ADAM zolmitriptan 1 mg, 1.9 mg, and 3.8 mg versus placebo. Co-primary endpoints were pain freedom and freedom from most bothersome other migraine-associated symptom 2 hours post-dose. Results Of patients treated with ADAM zolmitriptan 3.8 mg or placebo, 41.5% and 14.2%, respectively were pain-free 2 hours post-dose ( p = 0.0001) and 68.3% and 42.9% were free from their most bothersome other symptom ( p = 0.0009). Due to the fixed sequential testing methodology, formal statistical significance was not established for secondary endpoints. However, the proportion of patients who were photophobia-free, phonophobia-free, and nausea-free at 2 hours post-dose was higher in the ADAM zolmitriptan 3.8 mg group compared with placebo, as were the percentages of patients who were pain-free, and who experienced pain relief up to 48 hours post-dose. Systemic adverse events were consistent with previous triptan trials, and included dizziness, paresthesia, muscle tightness, and nausea, all of which occurred in < 5% of patients in any group. Application site reactions were generally mild and resolved within 48 hours, although erythema and bruising persisted for longer periods in some patients. Conclusion ADAM zolmitriptan 3.8 mg provides effective relief of migraine headache and associated most bothersome symptoms compared with placebo, and is well-tolerated. ClinicalTrials.gov NCT02745392.
View details for DOI 10.1177/0333102417737765
View details for Web of Science ID 000425150600001
View details for PubMedID 29022755
View details for PubMedCentralID PMC5815423
Use of Most Bothersome Symptom as a Co-Primary Endpoint in an Acute Treatment of Migraine Trial
SAGE PUBLICATIONS LTD. 2017: 361–62
View details for Web of Science ID 000416844600055
Post Hoc Subanalysis of Two Randomized, Controlled Phase 3 Trials Evaluating Diclofenac Potassium for Oral Solution: Impact of Migraine-Associated Nausea and Prior Triptan Use on Efficacy
2017; 57 (5): 756–65
To determine whether baseline nausea or prior triptan treatment for migraine impact the effectiveness of diclofenac potassium for oral solution in treating acute migraine.A great deal of variability exists in patients' response to migraine medications. Migraine-associated nausea is common and debilitating and can reduce the effectiveness of oral medications. It may cause patients to delay taking oral medications, which is known to diminish therapeutic outcomes, or to avoid taking them altogether. Gastroparesis, which may be associated with nausea, also inhibits drug absorption, resulting in lower bioavailability. Studies have shown that having nausea at the time of drug administration predicts a poorer response to triptan treatment. It is of interest to understand how effective other migraine medications are in patients with a poor response to triptans.Data from two randomized, double-blind, placebo controlled trials were pooled and post hoc subgroup analyses were performed in patients with and without nausea at baseline, and in patients with and without prior triptan treatment. Efficacy assessments included the percentage of patients who, at 2 hours postdosing, were headache pain-free (2hPF, primary endpoint), without photophobia, without phonophobia, without nausea, or without a severe degree of disability. A Cochran-Mantel-Haenszel test, stratified by analysis center was used to evaluate treatment effect. Effects of nausea or prior triptan use were determined using logistic regression with factors of treatment group, analysis center, nausea or prior triptan use at time of dosing, and interaction of treatment group by nausea or prior triptan use at time of dosing.The modified intent to treat population consisted of 1272 patients, 644 on active drug and 628 on placebo. The majority of patients (85%) were female. At the time of dosing, 783 (62%) patients reported nausea with the treated attack. Prior triptan use was recorded in 570 (45%). For headache pain, nausea, photophobia, and phonophobia, patients in the active treatment group had a statistically significantly better response than those receiving placebo, regardless of whether they had nausea at baseline. In logistic regression analysis only treatment group predicted a response for these parameters with no detectable group interaction. Baseline nausea, as well as treatment group, predicted whether patients recorded severe disability at 2 hours. While patients in the active treatment group were significantly more likely to be headache pain-free at 2 hours after dosing, whether or not they had previously been treated with triptan, more triptan-naïve patients (30%) than triptan-experienced patients (20%) were headache pain-free. Interestingly, in the placebo groups, triptan-naïve patients were also more likely to be PF (14% vs 7%). In the logistic regression analysis, treatment group predicted a headache pain response, triptan use predicted a lack of response, and there was no interaction between the two. Prior triptan use did not predict any of the other outcome measures.Nausea at the time of dosing does not diminish the effectiveness of diclofenac potassium for oral solution. The rapid absorption profile may enhance the effectiveness in patients with nausea. Prior triptan use predicted poorer headache response at 2 hours postdose, suggesting the possibility of a subset of patients who are more likely to be refractory to both triptans and diclofenac. Diclofenac potassium for oral solution is effective in triptan-naïve patients but no reliable inference can be made from this study as to about how to order treatment.
View details for DOI 10.1111/head.13073
View details for Web of Science ID 000400179100009
View details for PubMedID 28386945
View details for PubMedCentralID PMC5434944
Effect of Perioperative Gabapentin on Postoperative Pain Resolution and Opioid Cessation in a Mixed Surgical Cohort: A Randomized Clinical Trial.
Guidelines recommend using gabapentin to decrease postoperative pain and opioid use, but significant variation exists in clinical practice.To determine the effect of perioperative gabapentin on remote postoperative time to pain resolution and opioid cessation.A randomized, double-blind, placebo-controlled trial of perioperative gabapentin was conducted at a single-center, tertiary referral teaching hospital. A total of 1805 patients aged 18 to 75 years scheduled for surgery (thoracotomy, video-assisted thoracoscopic surgery, total hip replacement, total knee replacement, mastectomy, breast lumpectomy, hand surgery, carpal tunnel surgery, knee arthroscopy, shoulder arthroplasty, and shoulder arthroscopy) were screened. Participants were enrolled from May 25, 2010, to July 25, 2014, and followed up for 2 years postoperatively. Intention-to-treat analysis was used in evaluation of the findings.Gabapentin, 1200 mg, preoperatively and 600 mg, 3 times a day postoperatively or active placebo (lorazepam, 0.5 mg) preoperatively followed by inactive placebo postoperatively for 72 hours.Primary outcome was time to pain resolution (5 consecutive reports of 0 of 10 possible levels of average pain at the surgical site on the numeric rating scale of pain). Secondary outcomes were time to opioid cessation (5 consecutive reports of no opioid use) and the proportion of participants with continued pain or opioid use at 6 months and 1 year.Of 1805 patients screened for enrollment, 1383 were excluded, including 926 who did not meet inclusion criteria and 273 who declined to participate. Overall, 8% of patients randomized were lost to follow-up. A total of 202 patients were randomized to active placebo and 208 patients were randomized to gabapentin in the intention-to-treat analysis (mean [SD] age, 56.7 [11.7] years; 256 (62.4%) women and 154 (37.6%) men). Baseline characteristics of the groups were similar. Perioperative gabapentin did not affect time to pain cessation (hazard ratio [HR], 1.04; 95% CI, 0.82-1.33; P = .73) in the intention-to-treat analysis. However, participants receiving gabapentin had a 24% increase in the rate of opioid cessation after surgery (HR, 1.24; 95% CI, 1.00-1.54; P = .05). No significant differences were noted in the number of adverse events as well as the rate of medication discontinuation due to sedation or dizziness (placebo, 42 of 202 [20.8%]; gabapentin, 52 of 208 [25.0%]).Perioperative administration of gabapentin had no effect on postoperative pain resolution, but it had a modest effect on promoting opioid cessation after surgery. The routine use of perioperative gabapentin may be warranted to promote opioid cessation and prevent chronic opioid use. Optimal dosing and timing of perioperative gabapentin in the context of specific operations to decrease opioid use should be addressed in further research.clinicaltrials.gov Identifier: NCT01067144.
View details for PubMedID 29238824
- In reply. Anesthesiology 2014; 121 (2): 424-426
Sacroiliac Joint Radiofrequency Ablation with a Multi lesion Probe: A Case Series of 60 Patients
ANESTHESIA AND ANALGESIA
2014; 119 (2): 460–62
This retrospective case series of patients with refractory sacroiliac joint (SIJ) pain presents our first 77 SIJ radiofrequency ablation (RFA) procedures performed with a multilesion probe. Of these, 16 (20.8%) provided no relief; 55 (71.4%) provided >50% pain relief at 6 weeks; 42 (54.5%, 95% confidence interval, 42.8%-65.8%) provided >50% pain relief at 6 months; and 12 (15.6%) continued to provide >50% pain relief at 1 year. These results compare favorably to those published using other RFA techniques. In conclusion, more than half of our patients with refractory SIJ pain received some pain relief for at least 6 months after RFA.
View details for DOI 10.1213/ANE.0000000000000282
View details for Web of Science ID 000339455900029
View details for PubMedID 25046790
Self-Loathing Aspects of Depression Reduce Postoperative Opioid Cessation Rate
2014; 15 (6): 954-964
We previously reported that increased preoperative Beck Depression Inventory II (BDI-II) scores were associated with a 47% (95% CI 24%-64%) reduction in the rate of opioid cessation following surgery. We aimed to identify the underlying factors of the BDI-II (affective/cognitive vs somatic) associated with a decreased rate of opioid cessation after surgery.We conducted a secondary analysis of the data from a previously reported prospective, longitudinal, observational study of opioid use after five distinct surgical procedures (total hip replacement, total knee replacement, thoracotomy, mastectomy, and lumpectomy) in 107 patients. The primary endpoint was time to opioid cessation. After exploratory factor analysis of the BDI-II, mean summary scores were calculated for each identified factor. These scores were evaluated as predictors of time to opioid cessation using Cox proportional hazards regression.The exploratory factor analysis produced three factors (self-loathing symptoms, motivational symptoms, emotional symptoms). All three factors were significant predictors in univariate analysis. Of the three identified factors of the BDI-II, only preoperative self-loathing symptoms (past failure, guilty feelings, self-dislike, self-criticalness, suicidal thoughts, worthlessness) independently predicted a significant decrease in opioid cessation rate after surgery in the multivariate analysis (HR 0.86, 95% CI 0.75-0.99, P value 0.037).Our results identify a set of negative cognitions predicting prolonged time to postoperative opioid cessation. Somatic symptoms captured by the BDI-II were not primarily responsible for the association between preoperative BDI-II scores and postoperative prolonged opioid use.
View details for DOI 10.1111/pme.12439
View details for Web of Science ID 000338025900009
View details for PubMedCentralID PMC4083472
- Perioperative Gabapentinoids Choice of Agent, Dose, Timing, and Effects on Chronic Postsurgical Pain ANESTHESIOLOGY 2013; 119 (5): 1215-1221