February 22, 2023: In This Week’s PCT Grand Rounds, an Inclusive, Real-World S2302 Pragmatica-Lung

Headshots of Dr. Konstantin Dragnev and Dr. Karen ReckampIn this Friday’s PCT Grand Rounds, Dr. Konstantin Dragnev and Dr. Karen Reckamp will present “S2302 Pragmatica-Lung: New Directions for Decreasing Burden and Increasing Inclusion in NCTN Clinical Trials.”

The Grand Rounds session will be held on Friday, February 24, 2023, at 1:00 pm eastern.

S2302 Pragmatica-Lung is pragmatic clinical trial testing the effect of ramucirumab and pembrolizumab vs standard treatment on overall survival among patients whose non-small-cell lung cancer has advanced after immunotherapy and chemotherapy. The trial is being conducted in the National Cancer Institute’s National Clinical Trials Network of more than 2000 academic and community clinical sites.

Dragnev is a professor of medicine and the Irene Heinz Given Professor in Pharmacology in the Dartmouth Geisel School of Medicine and associate director for clinical research at the Dartmouth Cancer Center. Reckamp is a professor in medicine, director of the Division of Medical Oncology, and associate director of clinical research at Cedars-Sinai Cancer Center.

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February 7, 2023: FDA Issues Draft Guidance for Use of Real-World Data in Externally Controlled Trials

The US Food and Drug Administration last week issued draft guidance for the use of “externally controlled clinical trials” to provide evidence of the safety and effectiveness of drugs and biologics. An externally controlled trial uses patient-level data from a source outside the clinical trial—such as a registry, electronic health records, or administrative claims data—to provide a historical or concurrent control group for the study.

Reviewers are asked to submit written comments on the draft guidance by May 2, 2023. Read the draft guidance.

Externally controlled trials can be useful when it would not be feasible or ethical to use an internal control in the study, such as in studies of populations with rare diseases. The FDA issued the draft guidance as part of a series of guidance documents under its Real-World Evidence Program to satisfy a mandate under the 21st Century Cures Act.

February 1, 2023: This Week in PCT Grand Rounds, Insights From the NITRIC Trial in Young Children

Headshot of Luregn SchlapbachIn this Friday’s PCT Grand Rounds, Professor Luregn Schlapbach of the University Children’s Hospital Zurich will present “Pragmatic Trials for Children With Congenital Heart Disease: Insights From the NITRIC Trial.”

The Grand Rounds session will be held on Friday, February 3, 2023, at 1:00 pm eastern.

Schlapbach is head of intensive care and neonatology at the University Children’s Hospital Zurich and a researcher at the University of Queensland. He will discuss the design and results of the NITRIC trial, which examined the effect of nitric oxide on children undergoing cardiac surgery on cardiopulmonary bypass.

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January 18, 2023: PCT Grand Rounds Will Spotlight the EVOLVE-MI Pragmatic Trial

Headshot of Mikhail KosiborodIn this Friday’s PCT Grand Rounds, Mikhail Kosiborod of the University of Missouri-Kansas City will present “Collaborative Pragmatic Trials in Action: EVOLVE-MI.”

The Grand Rounds session will be held on Friday, January 20, 2023, at 1:00 pm eastern.

Kosiborod is a cardiologist, the vice president of research at Saint Luke’s Health System, and a professor of medicine at the University of Missouri-Kansas City. EVOLVE-MI is a pragmatic clinical trial evaluating the impact of rapid and intensive cholesterol lowering in patients who receive evolocumab within 10 days of a non-ST-elevation myocardial infarction or ST-elevation myocardial infarction.

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Grand Rounds January 6, 2023: Outpatient Treatment of COVID-19 With Metformin, Ivermectin, or Fluvoxamine: 10-Month Follow-up and Effects on Developing Long COVID (Carolyn Bramante, MD, MPH; Thomas Murray, PhD)

Speakers

Carolyn Bramante, MD, MPH
Division of General Internal Medicine
Departments of Internal Medicine and Pediatrics
Core faculty in the Program in Health Disparities Research and the Center for Pediatric Obesity Medicine
University of Minnesota Medical School

Thomas Murray, PhD
Division of Biostatistics
Coordinating Centers for Biometric Research
University of Minnesota School of Public Health

 

 

Keywords

COVID-19; Long COVID; COVID-OUT; Metformin; Ivermectin; Fluvoxamine

 

Key Points

  • The COVID-OUT Trial was a multi-arm remotely delivered, de-centralized Phase III clinical trial conducted at 6 institutions including 1431 patients with overweight or obesity, designed to test distinct treatment of COVID-19 with Metformin, Fluvoxamine, and Ivermectin. Arms of the trial included 6 groups: (1) metformin and fluvoxamine, (2) metformin and ivermectin, (3) metformin and placebo, (4) placebo and fluvoxamine, (5) placebo and ivermectin, (6) placebo and placebo.
  • The primary outcome was a binary, 4-part composite outcome of occurrence of severe COVID-19, defined as hypoxia, emergency department visit, hospitalization, or death. Patients were followed for 10 months after enrollment.
  • Long COVID was determined by patient-report of clinician-diagnosed Long COVID.
  • Data on Metformin plus placebo show an absolute risk reduction of 4.4% for Long COVID diagnosis at 300 days. There was a consistent direction of effect of Metformin across subgroups and no evidence of heterogeneity of treatment effect.
  • Diabetes may be a risk factor for severe COVID-19. New observational and preclinical data from patients with prediabetes and PCOS suggest there may be a dose dependent effect of metformin against SARS-CoV-2.
  • Metformin is safe, well tolerated, and familiar to providers.
  • Some limitations of the study include lack of diversity in patient population, methods of ascertainment of Long COVID that may under- or over-ascertain Long COVID, internal validity of oxygen data, and self-report of medication adherence.
  • Only 3.8% of people in the study who said they had Long COVID received treatment for Long COVID. The COVID-OUT trial data don’t suggest that Metformin will treat Long COVID in someone who already has Long COVID, but there are mechanisms that suggest it may be worth investigating.

 

Discussion Themes

– We did internally look at an unadjusted comparison of vaccinated vs unvaccinated participants, but this comparison is confounded and not the focus of this work. In the future we will do a full observational analysis predicting Long COVID using these subgroups..

– Earlier treatment versus later treatment with Metformin seems to benefit patients..

 There may be other medications in the space of diabetes that may have anti-inflammatory mechanisms that could be relevant to COVID-19 treatment. GLP-1 receptor agonists may have anti-inflammatory and immune modulatory effects. Also, DPP-4 inhibitors also have some beneficial anti-inflammatory effects. These medications are more expensive and may have a more difficult method of delivery, but could be studied to determine their effect on COVID-19.

 

LEARN MORE

Learn more about the COVID-Out trial.

Read the COVID-OUT trial results paper.

 

Tags

#pctGR, @Collaboratory1

Grand Rounds November 4, 2022: The CardioNerds Clinical Trials Network: Pairing Equitable Enrollment with Trainee Development (Amit Goyal, MD, MAS)

Speakers

Amit Goyal, MD, MAS
Interventional/Structural Fellow, Cleveland Clinic
Cofounder of CardioNerds

 

 

Keywords

Clinical Trial, Medical Education

 

Key Points

  • The goal of the CardioNerds Clinical Trials Network is to pair equitable enrollment with trainee development. CardioNerds started as an educational podcast, which in the first month had 5,000 downloads and now has had more than 3 million downloads in 192 countries. The success of the podcast shows the need and value for asynchronous training.
  • The mission and the people involved with CardioNerds are the key ingredients for its success. The mission is to democratize cardiovascular education by creating and disseminating education, fostering wellness and humanism, promoting diversity, equity and inclusion, providing mentorship and sponsorship, and invigorating a love of cardiovascular science.
  • The biggest inflection point for CardioNerds was COVID-era recruitment, when residents were asked to decide where to train for fellowship without having in-person visits. CardioNerds collaborated with ACA to invite every fellowship to share case-based learning and the training opportunities of their program. They also included a message from the fellowship program director or leadership. Forty-four programs participated.
  • CardioNerds identified a need to develop a pilot clinical trials network for the PARAGLIDE-HF trial, a multicenter, randomized, double-blind, double-dummy, parallel group, active controlled study to evaluate the effect of sacubitril/valsartan verses valsartan on changes in NT-proBNP, safety, and tolerability in HFpEF patients with a WHF event who have been stabilized and initiated at the time of or within 30 days post-decompensation.
  • Like many trials during the COVID-19 pandemic, there were significant challenges and recruitment delays. To address these challenges, we decided to work with the CardioNerds network with a goal of pairing trial enrollment with trainee professional development. Among trial sites with affiliated programs, we invited program directors to nominate fellows to participate. We engaged fellows by making them part of the research team, ensured mentorship, networking, etc. We built the first trainee-based CardioNerds Clinical Trials Network that enhanced recruitment and education.
  • The network ended up with 20 sites and 22 trialists. The fellows were responsible for 45% of enrollment during the time of the trial. The CardioNerds fellows enrolled 54% women compared to 45% non-fellow enrolled and 71% BIPOC compared to 23% non-fellow enrolled patients. The network also built a community of fellows who took great pride in the work they were doing. For every of the 70+ recruitments an email went out celebrating the work of the fellows and site mentors, which reinvigorated interest and enthusiasm among the site PIs, who had the opportunity to mentor the next generation of trialists.
  • In the future, we would like to study this in greater detail and find out what happened at CardioNerd sites compared to other sites. We would like to do a qualitative study for everyone involved and understand the career impact for the fellows.

Learn more

Visit the CardioNerds website.

Discussion Themes

-What did this activity displace in a busy cardiology fellow’s day? What we tried to emphasis was engaging cardiovascular fellows in year 2 or 3 when there are less clinical responsibilities and more elective time. There are a lot of ways to use the available time. The emphasis was identifying fellows who are interested in developing careers in clinical science. We did not want the fellows to take the place of the site coordinators but to use their experience taking care of the patient. It was matched to their career goals, and it fit into the rubric of what they are already doing, caring for patients and being involved in education.

-Why do you think fellows were more successful in enrolling women and BIPOC? There can be a general level of mistrust. If a patient is approached by a fellow, the perspective of the fellow is to prioritize patient care, so there is a built-in level of trust that may come with that and is something we want to explore more. We asked site PIs to prioritize nominating fellows who were women and URMs. A lot of this was also related to the sites that were involved.

Tags

#pctGR, @Collaboratory1

October 19, 2022: This Week in PCT Grand Rounds: Protecting Patients and Research From Disinformation, Cyberthreat, and Choice

Headshots of Eric Perakslis and Andrea DowningIn this Friday’s PCT Grand Rounds, Eric Perakslis of Duke University and Andrea Downing of The Light Collective will present “Disinformation, Cyberthreat, and Choice: Protecting Patients and Clinical Research From the Digital Triple Threat.” The Grand Rounds session will be held on Friday, October 21, 2022, at 1:00 pm eastern.

A professor of population health sciences at Duke University, Perakslis is the chief science and digital officer of the Duke Clinical Research Institute and the chief research technology strategist in the Duke University School of Medicine. Downing is a cofounder of The Light Collective, a coalition of patient networks that advocates for the rights and interests of patient communities in healthcare technology.

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October 5, 2022: PCT Grand Rounds to Feature Randomized Trial of Intraoperative Anesthesia Handovers

Headshot of Dr. Melanie Meersch-DiniIn this Friday’s PCT Grand Rounds, Dr. Melanie Meersch-Dini of University Hospital Münster (Germany) will present “Impact of Handovers of Anesthesia Care on Morbidity and Mortality.” The Grand Rounds session will be held on Friday, October 7, 2022, at 1:00 pm eastern.

Dr. Meersch-Dini will discuss the results of the HandiCAP trial (Impact of Handover of Anesthesia Care on Adverse Postoperative Outcomes), a parallel-group, randomized clinical trial of intraoperative handover of anesthesia care in 12 centers in Germany.

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September 28, 2022: PCT Grand Rounds to Feature CTTI’s Digital Health Trials Hub

Headshots of Marianne Chase and Dr. Jörg GoldhahnIn this Friday’s PCT Grand Rounds, Marianne Chase of Massachusetts General Hospital and Dr. Jörg Goldhahn of ETH Zurich will present “CTTI’s Digital Health Trials Hub: Multi-Stakeholder Resources to Conduct Effective Digital Health Trials.” The Grand Rounds session will be held on Friday, September 30, 2022, at 1:00 pm eastern.

Chase is senior director for clinical trial operations at Mass General’s Neurological Clinical Research Institute. Goldhahn is medical director of the Institute for Translational Medicine at ETH Zurich.

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August 30, 2022: FDA Announces Webinar on Patient-Focused Drug Development Draft Guidance

FDA logoThe US Food and Drug Administration (FDA) will host a webinar on September 9 for industry, patient groups, and other interested stakeholders to discuss and answer questions about the draft guidance, Patient-Focused Drug Development: Selecting, Developing, or Modifying Fit-for-Purpose Clinical Outcome Assessments.

The draft guidance, known as “Guidance 3,” is the third of 4 methodological guidance documents for patient-focused drug development that describe how patients, caregivers, researchers, medical product developers, and others can collect and submit patient experience data and other relevant information to be used for medical product development and regulatory decision making. Guidance 3 discusses approaches to selecting, modifying, developing, and validating clinical outcome assessments to measure outcomes of importance to patients in clinical trials.

Register for the webinar at https://www.eventbrite.com/e/public-webinar-patient-focused-drug-development-pfdd-draft-guidance-3-tickets-397246183027.