Publications on COVID-19 from ACTG Investigators
Harvard CTUs: Dr. Paul Sax has authored a number of articles to answer questions and to bring an informed perspective to the continued discussions surrounding everyday life and “what to know” about COVID-19. Read below!
Drs. Rajesh Gandhi from the Massachusetts General Hospital CTU and Carlos del Rio from the Emory ACTG co-authored a piece on mild to moderate coronavirus in the New England Journal of Medicine (NEJM) published Friday, April 24.
Northwestern University: ACTG investigator Dr. Babafemi Taiwo, Chief of Infectious Diseases at Northwestern University, was interviewed by CNN about the early results of a study evaluating the drug remdesivir to treat COVID-19. ACTG investigators continue to be on the frontlines of research across the country and the globe. Find the video here.
Stellenbosch University CTU – Cape Town, South Africa: Dr. Mark Cotton co-authored an article describing their early response as a designated COVID-19 provincial hospital. See the article below!
University of San Francisco:
From the University of California at San Francisco CTU, Drs. Monica Gandhi and Diane Havlir co-authored a piece on universal population-level masking in Open Forum Infectious Diseases and an editorial in the NEJM on mass asymptomatic testing in Skilled Nursing Facilities. Dr. Annie Luetkemeyer and Jay Dwyer, main CRC for the SF-Bay Area CTU, are setting up all of the randomized clinical trials for inpatients getting experimental COVID-19 therapy.
National Institutes of Health (NIH): A number of ACTG investigators were chosen to be a part of the new NIH COVID-19 guidelines panel, which issued initial guidelines on April 21, 2020 (these will be updated on an ongoing basis). ACTG investigators on the expert U.S. panel include Drs. Roger Bedimo, Ann Collier, Eric Daar, Rajesh Gandhi, Roy (Trip) Gulick, Jeffrey Lennox, Susanna Naggie, Susan Swindells and Pablo Tebas.
University of Puerto Rico CTU: Dr. Jorge Santana and colleagues at the University of Puerto Rico have formed a COVID-19 Medical Task Force which advises Governor Wanda Vázquez Garced on policy issues related to COVID-19, including measures to combat it, ensuring adequate supplies of personal protection equipment and informational materials on SARS-CoV-2.
CTU at Emory and Weill Cornell Medical College – New Jersey Medical School Clinical Trials Unit (WCMC-NJMs) CTU: Dr. Carlos del Rio from the Emory CTU and Dr. Rajesh Gandhi from the Harvard CTU published an article in the New England Journal of Medicine (NEJM) on mild to moderate COVID-19 and clinical management. Dr. Roy “Trip” Gulick and colleagues from the WCMC-NJMs CTU wrote an article for NEJM on severe COVID-19, including pathogenesis and medical management.
CTU at Harvard: Dr. Jonathan Li is helping to lead the COVID sample collection efforts at Brigham Women’s Hospital, Harvard CTU through the Massachusetts Consortium for Pathogen Readiness. “We’re collecting samples from hospitalized patients, outpatients, and convalescent patients. We’ve also broadened the focus of the Harvard Virology Specialty Laboratory to encompass COVID-related research, including implementing a quantitative SARS-CoV-2 viral load assay and performing whole viral sequencing.
CTU in Rhode Island: Our ACTG unit at The Miriam Hospital in Providence, RI contributed to the COVID effort by signing up for the Gilead Remdesivir trials (severe and moderate disease) in the middle of March. Drs. Karen Tashima, Natasha Rybak, and Martha Sanchez, study coordinator Pamela Poethke, RN, study nurse Helen Patterson, and regulatory assistant/data manager Dylan Canfield comprise the unit. “We needed to expand the team to manage enrollment and data entry. ID doctors in the Division stepped in quickly by becoming GCP certified, and we added additional research assistants to the team. We have enrolled close to 200 patients across two hospitals in Rhode Island that have treated the majority of the COVID-19 cases in the state. Many of our ID docs and fellows are now experienced in consenting in complex situations, and have learned a lot about clinical trials procedures. Our division, the Department of Medicine, and the hospital system has appreciated our unit for being able to ramp up quickly for the crisis.
University of Washington (UW) ACTU:
- Bob Coombs’ lab (ACTG VSL and the UW ACTU processing lab) has been repurposed and is performing SARS-Co-2 RNA testing as an extension of the UW Department of Laboratory Medicine efforts.
- Ann Collier is leading a UW-wide COVID-19 Clinical Research Review Working Group to help prioritize COVID-19 research requiring access to patients, specimens, and data at UW facilities. She is a member of the NIH’s COVID-19 Treatment Guidelines panel. She is participating in a UW-wide effort that is providing testing for residents of area nursing homes and assisted living facilities and is one of many volunteers to carry a “COVID pager” that provides back-up for our institution’s infection control staff.
- Rachel Bender-Ignacio also frequently carries a “COVID pager” that provides back-up for our institution’s infection control staff. She is one of the leaders for C5396, working locally to implement COVID-19 randomized clinical trials for inpatients and collaborating on observational COVID-19 data analysis projects.
Alabama CRS: At the Alabama CRS our research team was initially beset by COVID-19 with several members of our team developing active disease. Fortunately, all of our team members have recuperated and are back on the front lines helping local efforts to address the pandemic. Beyond research activities, our team has been very involved in local efforts to flatten the curve and prevent bad outcomes for our fellow Alabamians.
- Sonya Heath is leading efforts to develop antibody testing to identify individuals who would make potential donors for convalescent serum.
- Heath and Dr. Turner Overton are assisting with all COVID-19 related Employee Health issues. With close coordination with hospital leadership and local public health entities, they have markedly reduced infection among the University of Alabama Birmingham (UAB) faculty and staff.
- Beyond his on-line and media personality, Dr. Mike Saag and Dr. Overton have created an outpatient COVID clinic to reduce burden on the emergency room and provide a location to assess patients who are worsening at home.
- Our research staff have taken ownership of ongoing inpatient COVID clinical trials to test new medicines as they emerge.
- Given that necessity is the mother of invention, our team has partnered with the local community to assure access to PPE for our staff and the UAB community.
- Our team is also very involved in outreach efforts to marginalized populations and areas of Birmingham that have limited access to healthcare.
The experience of our team on the prevention and treatment of HIV has prepared us well to face this current crisis. To maintain spirits, Dr. Overton is sending out a daily pandemic song of the day. It is the little things that keep our spirits up in these trying times. “When the going gets weird, the weird turn pro.”-Hunter S. Thompson
Weill Cornell Medicine – New Jersey Medical School CTU: It is hard to comprehend what has happened in the last six weeks. New York and New Jersey have been hit with a tidal wave of SARS-CoV-2. The hospitals and their staff have been strained to meet the crushing demands of caring for those afflicted. Daily life is unbelievably different with almost every aspect being re-ordered. Some of us have become ill ourselves and some have lost loved ones to COVID-19. Fortunately, we are using our collective talent to make a difference.
Our accomplishments have been impressive. We have successfully transitioned the vast majority of our ongoing participants to remote follow-up. Our teams have pivoted to leading the COVID-19 clinical research efforts at our hospitals. We have implemented highly complex inpatient treatment protocols for those ill with COVID-19 at an astonishing pace. We have partnered with transfusion medicine to screen those recovered from COVID for plasma donation. We have implemented a large trial of healthcare worker prophylaxis against COVID. We have authored DHHS treatment guidelines for COVID.
Our new skill set includes video visits, electronic consents (CFR 21 part 11 compliant!!), being remotely monitored, BSL-2+ laboratory processing, blood donor screening, knowing the difference between N95 and KN95 and when to use purple wipes and when to use orange wipes. We have avoided being zoom-bombed and have started our daily huddles with a joke (usually terrible), all while flattening the curve and being together apart. Our teams have been incredibly productive, focused and supportive. Our research CABs have shown continued perseverance, knowledge, and support to each other and our teams, ensuring the fight against HIV continues and that our communities maintain needed connection and are informed about COVID-19.
We know that in this pandemic every site in our network is experiencing the same challenges to varying degrees. We know that some sites do not have as many resources to deal with the epidemic. For all sites, we hope for an Ro < 1 and that your COVID trials are closed for slow accrual. Stay safe!!
Socios En Salud Sucursal CRS – Lima, Peru: The team at Socios En Salud Sucursal CRS has provided a comprehensive guide to their response to COVID-19. See their efforts by following the link here!
BJGMC-JHU CRS in Pune, India: The COVID-19 pandemic presents real challenges for research teams around the world conducting clinical trials. The experience with TB studies underway at the Byramjee Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site (BJGMC-JHU CRS) in Pune, India, required swift action, agility, and innovation in ensuring that study participants continue to receive lifesaving care in the midst of a national lockdown.
The WHO has prioritized TB preventive therapy, including for household contacts of people with multidrug-resistant (MDR) TB, as a key strategy for controlling the epidemic. One study to prevent MDR-TB among household contacts of confirmed cases currently underway at the BJGMC-JHU CRS is a multinational, phase 3, randomized clinical trial to compare 26 weeks of Delamanid (DLM) versus 26 weeks of Isoniazid (INH) for preventing confirmed or probable active TB in high-risk household contacts. For this trial, titled Protecting Households on Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients (or PHOENIx), 19 index MDR-TB cases and 12 household contacts are enrolled.
Participants on study routinely receive enough medication to last until their next scheduled clinical visit. With visits cancelled due to the lockdown, and with recovery from COVID-19 likely to be prolonged, the PHOENIx Team needed to find alternate ways to distribute medication. Mail delivery was not an option, and asking research participants to pick up medication from the CRS or at designated locations within the community was deemed too risky.
Although the PHOENIx study protocol provides for an extended administration of therapy from 26 weeks to up to 34 weeks, the team considered that only as a last resort. With the lockdown imminent, the team was under considerable pressure to develop and implement a plan to deliver enough medication to last participants through June15. While it might appear fairly straightforward, there were considerable logistical and safety issues to address:
- Specific measures were planned for, and the team notified participants of what to expect.
- Online prescriptions were sent to the pharmacist for filling.
- Personal protective equipment (PPE)—including gloves, N-95 masks, and hand sanitizer—was provided for staff going into the field. The team decided to use glasses/goggles and helmets rather than full PPE kits, because of the optics. There is considerable stigma associated with disease, and teams presenting to households in such gear could cause problems for participants in their communities.
- Online training was provided for the safe use and disposal of protective equipment.
- Each outreach counselor was assigned a specific route in Pune or Pimpri-Chinchwad city, and a “drop and run” protocol was implemented in order to minimize personal interactions.
- The day before the drop, participants were contacted by the Outreach team, and phone screenings were conducted for COVID-19 related symptoms.
The Study team, Outreach team, Pharmacy team, and Support team worked closely on all facets of planning and implementation. The operation was successful, and the clear communication with study participants inspired further confidence in the team’s commitment to their health and wellbeing.
The planning that went into ensuring participants for one study were provided for during a health emergency served as a template for other studies at the BJGMC-JHU CRS. Specifically, the process was used for participants of the REPRIEVE study (Randomized trial to Prevent Vascular Events in HIV), the VESTED study (Virologic Efficacy and Safety of ART Combinations with TAF/TDF, EFV, and DTG) and IMPAACT 2005 (Study of Pharmacokinetic, Safety and Tolerability of Delamanid in Combination with OBR for MDR-TB in Children).
As of April 9, 2020, 25 research participants from different studies were approached for distribution of study medication during COVID-19 lockdown in India. Six outreach counselors, 2 pharmacists, 2 support staff, and many background team leaders worked to ensure that participants continued receiving care during the emergency.
COVID-19 Related Trials from the ACTG
The ACTG has launched ACTIV-2 Outpatient Monoclonal Antibodies and Other Therapies Trial. ACTIV-2 includes both phase 2 and phase 3 evaluations of multiple promising investigational agents for treating early COVID-19 in a single trial. There is currently no approved vaccine or therapeutic to prevent or treat COVID-19.
ACTIV-2 will evaluate the safety and efficacy of investigational agents to treat adults who have COVID-19 illness but do not require hospitalization. The study will also enable researchers to assess the correlation between changes in viral shedding and clinical outcomes, leading to a better understanding of whether effective medications can reduce or halt the transmission of SARS-CoV-2 (the virus that causes COVID-19) to others. ACTIV-2 is a randomized, blinded, controlled adaptive platform that allows promising investigational agents to be added and removed over the course of the study, in order to efficiently test a variety of new agents against placebo within the same trial infrastructure.
For information about enrolling in the trial, please click here.
ACTG recently announced that it has stopped enrolling A5395, our clinical trial evaluating whether hydroxychloroquine and azithromycin can prevent hospitalization and death from COVID-19. This action was taken when it was determined that the rate of participant enrollment was insufficient for the trial to meet its objectives in a timely manner. No safety concerns were associated with the trial. ACTG remains highly involved in efforts to address COVID-19, having been asked to lead a Master Adaptive protocol under the Accelerating COVID-19 Therapeutic Interventions and Vaccine (ACTIV) Operation Warp Speed. This trial (ACTG 5401 or ACTIV-2) will evaluate multiple monoclonal antibodies and other small molecules for outpatient COVID treatment. The trial is set to open at the end of July.
The ACTG is working with Novartis to conduct additional clinical trials. Information can be found here.