COVID-19

July 27, 2022: COVID-19 Grand Rounds to Feature Interferon Therapy Results From TOGETHER Trial

Posted on by Damon Seils

Head shots of Dr. Edward Mills and Dr. Jeffrey GlennIn this Friday’s COVID-19 Grand Rounds, Dr. Edward Mills of McMaster University and Dr. Jeffrey Glenn of Stanford University will present “Effect of Early Treatment With Single-Dose Pegylated Interferon Lambda Among Patients With COVID-19: Results From The TOGETHER Trial.”

The TOGETHER trial is a randomized adaptive platform trial investigating several treatments for COVID-19.

The Grand Rounds session will be held on Friday, July 29, at 1:00 pm eastern. Join the online meeting.

The NIH Pragmatic Trials Collaboratory Coordinating Center is using its popular Grand Rounds platform to share late-breaking research and promote resources in support of clinical researchers affected by the COVID-19 public health emergency. For previous COVID-19 Grand Rounds, and more news and resources related to the COVID-19 public health emergency, see the COVID-19 Resources page.

Grand Rounds July 15, 2022: Overview of Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Public-Private Partnership and Lessons Learned (Stacey J. Adam, PhD)

Posted on by Elizabeth Mccamic

Speaker

Stacey J. Adam, PhD
Associate Vice President, Research Partnerships
Foundation for the NIH

 

 

Keywords

ACTIV, COVID-19, FNIH

 

Key Points

  • The normal timeline for public-private partnerships is around 9 months of planning. ACTIV was stood up in about a month, launching on April 17, 2020, to develop a coordinated research response to speed COVID-19 treatment and vaccine options. There were four ACTIV fast-track focus areas: vaccines, preclinical, clinical trial capacity, and therapeutics – clinical.
  • In the therapeutics arm, the most promising therapeutic agents for COVID-19 were prioritized. Candidate agents were triaged based on concurrent clinical trials, completion of a multiple ascending dose study, and availability of preclinical data before being scored based on predefined criteria. From this review, 11 ACTIV master protocols were developed.
  • Having the ability to use the resources from the public and private sectors as much as possible, having sufficient funding and staffing, and having clear communication were all quintessential to getting things running quickly.
  • Since the protocols have launched, 20,000+ patients have enrolled at more than 620 sites across numerous networks, 11 protocols were developed, 10 launched, with 26 publications across 13 journals. The team reviewed 800 candidates over 2 years time. We selected 35 and completed testing of 27 of them. Six agents showed really good results and either changed clinical practice or showed efficacy and improved patient care. Five agents are still in testing.
  • Each protocol has had many lessons learned. Across all is the need for clear communication, resources, and partnerships.

Discussion Themes

–How did the public-private partnership contributed to the success of ACTIV? Having the companies at the table, bringing the resources (man power, willingness to test, openness of conversation) was amazing and contributed to success of the program.

–Foundation for NIH was involved from the beginning because we had successfully done the public-private partnerships for other initiatives, we had the stakeholder relationships to get everyone to the table, and our involvement allowed for rapid, targeted donations from private sector.

 

Read more in Annals of Internal Medicine and Critical Care Medicine.

View the Summary of NIH-Funded ACTIV/ACTIV-Associated Clinical Trials.

Tags

#pctGR, @Collaboratory1

July 20, 2022: ACTIV-6 Reaches 1 Year, Will Share Results in COVID-19 Grand Rounds

Posted on by Damon Seils

Headshot of Dr. Susanna NaggieIn this Friday’s COVID-19 Grand Rounds, Dr. Susanna Naggie of Duke University will present “ACTIV-6: One Year Later and Trial Results for Ivermectin-400 and Inhaled Fluticasone.”

ACTIV-6 is a nationwide, double-blind study evaluating the effectiveness of repurposed medications in reducing symptoms of mild to moderate COVID-19 in outpatients.

The Grand Rounds session will be held on Friday, July 22, at 1:00 pm eastern. Join the online meeting.

The NIH Pragmatic Trials Collaboratory Coordinating Center is using its popular Grand Rounds platform to share late-breaking research and promote resources in support of clinical researchers affected by the COVID-19 public health emergency. For previous COVID-19 Grand Rounds, and more news and resources related to the COVID-19 public health emergency, see the COVID-19 Resources page.

Grand Rounds July 22: ACTIV-6: One Year Later and Trial Results for Ivermectin-400 and Inhaled Fluticasone (Susanna Naggie, MD, MHS)

Speaker:

Susanna Naggie, MD, MHS
Professor of Medicine
Vice Dean for Clinical Research
Duke University School of Medicine
Infectious Diseases Research
Duke Clinical Research Institute

 

Topic: ACTIV-6: 1-year Later and Trial Results for Ivermectin-400 and Inhaled Fluticasone
Date: Friday, July 22, 2022, 1:00-2:00 p.m. ET

 

Meeting Info: To check whether you have the appropriate players installed for UCF (Universal Communications Format) rich media files, go to https://dukemed.webex.com/dukemed/systemdiagnosis.php.

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July 13, 2022: Lessons From the ACTIV Public-Private Partnership to Be Shared in COVID-19 Grand Rounds

Posted on by Damon Seils

Headshot of Dr. Stacey AdamIn this Friday’s COVID-19 Grand Rounds, Dr. Stacey Adam of the Foundation for the NIH will present “Overview of Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Public-Private Partnership and Lessons Learned.”

The NIH announced the ACTIV public-private partnership in April 2020 to develop a coordinated research strategy for speeding development of COVID-19 treatments and vaccines. The partnership is coordinated by the Foundation for the NIH and brings together the Biomedical Advanced Research and Development Authority, the Centers for Disease Control and Prevention, and the US Food and Drug Administration, the Department of Defense, the Department of Veterans Affairs, the Countermeasures Acceleration Group, the European Medicines Agency, and representatives from academia, philanthropic organizations, and biopharmaceutical companies.

The Grand Rounds session will be held on Friday, July 15, at 1:00 pm eastern. Join the online meeting.

The NIH Pragmatic Trials Collaboratory Coordinating Center is using its popular Grand Rounds platform to share late-breaking research and promote resources in support of clinical researchers affected by the COVID-19 public health emergency. For previous COVID-19 Grand Rounds, and more news and resources related to the COVID-19 public health emergency, see the COVID-19 Resources page.

Grand Rounds July 8, 2022: Results From the COVID-OUT Trial, A Phase-3 Trial of Outpatient Treatment for Covid-19 Using Metformin, Ivermectin, and Fluvoxamine (Carolyn Bramante, MD, MPH; Thomas Murray, PhD; Jared Huling, PhD)

Posted on by Elizabeth Mccamic

Speakers

Carolyn Bramante, MD, MPH
Assistant Professor, General Internal Medicine and Pediatrics
Core Faculty, Center for Pediatric Obesity Medicine
Core Faculty, Program for Health Disparities Research
University of Minnesota Medical School

Thomas Murray, PhD
Assistant Professor of Biostatistics
Division of Biostatistics
University of Minnesota School of Public Health

Jared Huling, PhD
Assistant Professor of Biostatistics
Division of Biostatistics
University of Minnesota School of Public Health

 

 

Keywords

COVID-19, COVID-OUT

 

Key Points

  • The COVID-OUT Trial is a remotely delivered, Phase 3, de-centralized clinical trial at 6 participating institutions to see if Ivermectin, Metformin or Fluvoxamine would prevent severe COVID-19. The primary outcome was a 4-part composite: hypoxemia on a home oxygen monitor, ED visit, hospitalization or death due to COVID-19.
  • The dosing for the drugs during the trial was Ivermectin 390 (470mcg/kg/day x 3 days), Metformin titration to 1,500mg/day over 7 days, and Fluvoxamine 50mg.
  • Trial participants were adults ages 30-85, who tested positive for SARS-CoV-2 within 3 days, with fewer than 7 days of symptoms, no known prior infection with SARS-CoV-2, no severe kidney, liver, or heart failure. Patients with diabetes or prediabetes were not excluded (except for those on insulin or sulfonylurea); pregnant patients were not excluded for the Metformin arm; the trial restricted participants to people who were overweight or obese to enrich the population for having a high risk of outcomes and for anti-inflammatory hypotheses around Metformin.
  • Initially, the randomization of the trial was 1:1 Metformin or Placebo. When Ivermectin and Fluvoxamine were added enrollment was even across 6 arms (except for pregnant participants). When the DSMB recommended stopping Fluvoxamine, the trial reduced to 4 arms.
  • The primary outcome of the trial was negative. Some aspects were a success, particularly delivery of study medication nation-wide within 1 day of consent. None of the medications appeared to have any effects on symptoms. A pre-specified secondary analysis of the primary outcome indicates a substantial reduction in ED visits, hospitalizations, and death from COVID-19 with Metformin.

Discussion Themes

-How did the trial handle recruitment? It was a huge challenge. We started only looking within the participating health system and sites. We used Google Ads and partnerships with some testing clinics. We worked together between the sites when there were issues with bandwidth at one of the sites, the main site would call those participants. We also kept equal focus on follow-up.

Learn more about COVID-OUT.

Tags

#pctGR, @Collaboratory1

July 6, 2022: Grand Rounds to Spotlight COVID-OUT Trial of Metformin, Ivermectin, and Fluvoxamine

Posted on by Damon Seils
Headshots of Drs. Carolyn Bramante, Thomas Murray, Jared Huling
Left to right: Dr. Carolyn Bramante, Dr. Thomas Murray, Dr. Jared Huling

In this Friday’s COVID-19 Grand Rounds, Dr. Carolyn Bramante, Dr. Thomas Murray, and Dr. Jared Huling of the University of Minnesota will present “Results From the COVID-OUT Trial, a Phase-3 Trial of Outpatient Treatment for COVID-19 Using Metformin, Ivermectin, and Fluvoxamine.”

The Grand Rounds session will be held on Friday, July 8, at 1:00 pm eastern. Join the online meeting.

The NIH Pragmatic Trials Collaboratory Coordinating Center is using its popular Grand Rounds platform to share late-breaking research and promote resources in support of clinical researchers affected by the COVID-19 public health emergency. For previous COVID-19 Grand Rounds, and more news and resources related to the COVID-19 public health emergency, see the COVID-19 Resources page.

Grand Rounds July 29: Effect of Early Treatment With Single-Dose Pegylated Interferon Lambda Among Patients With COVID-19: Results From the TOGETHER Trial (Edward Mills, PhD, FRCP; Jeffrey S. Glenn, MD, PhD)

Speakers:

Edward Mills, PhD, FRCP
Professor
Department of Health Research Methods, Evidence & Impact
McMaster University, Canada

Jeffrey S. Glenn, MD, PhD
Joseph D. Grant Professor and Professor of Microbiology and Immunology
Stanford University

Topic: Effect of Early Treatment With Single-Dose Pegylated Interferon Lambda Among Patients With COVID-19: Results From the TOGETHER Trial
Date: Friday, July 29, 2022, 1:00-2:00 p.m. ET

Meeting Info: To check whether you have the appropriate players installed for UCF (Universal Communications Format) rich media files, go to https://dukemed.webex.com/dukemed/systemdiagnosis.php.

To join the online meeting:
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Click ‘Connect to Audio”
Choose ‘Computer Audio’ or ‘I will call in’.
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June 29, 2022: Pragmatic Trials Experienced Significant Impacts of COVID-19 on Trial Activities

Posted on by Damon Seils
Headshot of Dr. Emily O'Brien
Lead author Dr. Emily O’Brien

Pragmatic clinical trials experienced significant impacts of COVID-19 on trial activities, according to a survey of NIH Pragmatic Trials Collaboratory Trials published last month in Trials.

Since the beginning of the COVID-19 pandemic in March 2020, many of the NIH Collaboratory Trials have had to postpone recruitment, alter methods of participant engagement, and modify tools for research assessment and intervention delivery. Trial delays often created statistical challenges, especially for those using stepped-wedge designs.

Most of the study teams were able to work closely with healthcare system partners to adapt their study interventions. Some of the adaptations resulted in better participant outreach and the ability to study virtual intervention delivery methods. All of the NIH Collaboratory Trials were able to adapt to pandemic-related changes.

In a recent video interview, lead author Dr. Emily O’Brien praised the study teams.

“We certainly did see some degree of disruption, but I was impressed by the flexibility in the ability to adapt that all of our NIH Collaboratory Trial teams showed,” said O’Brien. “Some of them mentioned the support of having the [Core Working Groups] and consultations with experts in real time to be able to make adjustments,” she said.

The NIH Collaboratory published a tool last year to assist investigators in identifying impacts of the COVID-19 pandemic on ongoing pragmatic trials. The Statistical Analysis Plan Checklist for Addressing COVID-19 Impacts summarizes impacts on trial conduct that study teams should document, measure, analyze, and report.

Grand Rounds July 15: Overview of Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Public-Private Partnership and Lessons Learned (Stacey J. Adam, PhD)

Speaker:

Stacey J. Adam, PhD
Associate Vice President, Research Partnerships
Foundation for the NIH

 

Topic: Overview of Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Public-Private Partnership and Lessons Learned
Date: Friday, July 15, 2022, 1:00-2:00 p.m. ET

 

Meeting Info: To check whether you have the appropriate players installed for UCF (Universal Communications Format) rich media files, go to https://dukemed.webex.com/dukemed/systemdiagnosis.php.

To join the online meeting:
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Click ‘Connect to Audio”
Choose ‘Computer Audio’ or ‘I will call in’.
If using the ‘call in option’, follow the information from the dialog box that appears.
Be certain to use the Access Code AND the Attendee ID.

Troubleshooting:
If the URL above does not work, go to dukemed.webex.com and enter:
Meeting Number: 2622 682 0537
Meeting Password: 12345

For Audio ONLY:
Call-in toll number (US/Canada): 1-650-479-3207
Access code: 2622 682 0537

NOTE: For Toll-free users, the call-back (call me) services are also available.