The ACTIV COVID-19 Clinical Trials: 5 Things to Know

The Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative is currently conducting clinical trials to advance COVID-19 vaccines and therapeutics to both prevent COVID-19 and treat mild to life-threatening COVID-19 infection. The mission of ACTIV is to reduce the morbidity and mortality from COVID-19 and to accelerate the end of the SARS-CoV-2 outbreak.

ACTIV is a public-private partnership led by the National Institutes of Health (NIH), which leverages scientific innovation from across US government agencies, private pharmaceutical companies, academia, and philanthropic foundations. The Foundation for the National Institutes of Health provides logistical and management support to ACTIV. In addition to the NIH, collaborating agencies include the US Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority, the Department of Defense, and the Veterans Administration.

The ACTIV therapeutic trials were designed to address treatment needs across the spectrum of patient populations (from outpatient to critical care) matrixed by different therapeutics targets (eg, viral target vs host target). The ACTIV therapeutic protocols allow for rigorous assessment of safety and efficacy of candidate therapeutics in flexible, multi-stage, multi-arm, randomized controlled trial designs. Potential therapeutic candidates remain under investigation if they show promise of clinical benefit; they are dropped if data indicate that they are unlikely to be of clinical benefit (futility). The ACTIV trials also offer a seamless transition from phase 2 to phase 3 trials, and a gain in efficiency since multiple agents are compared with a common placebo.

Here are five things to know about the ACTIV trials.

1. ACTIV clinical trials are recruiting participants for outpatient and inpatient studies to identify safe and effective COVID-19 treatments.

Researchers continue to test a multitude of potential treatments that target COVID-19 pathogenesis in both outpatients with mild to moderate symptoms of COVID-19 and hospitalized patients with more severe symptoms. In the ACTIV trials researchers are investigating ways to:

• Test immune modulators for hospitalized patients to help them get better faster (ACTIV-1);

• Evaluate treatments that inhibit SARS-CoV-2 replication and/or attachment of SARS-CoV-2 to cells to decrease viral load and limit disease progression (ACTIV-2);

• Prevent patients with mild to moderate COVID-19 from progressing to the point where they need hospitalization (ACTIV-2);

• Help hospitalized patients with COVID-19 get home faster and stay home without needing readmission (ACTIV-3);

• Help patients with respiratory failure from COVID-19 reduce oxygen requirements and go home faster (ACTIV-3b);

• Test anticoagulants and antiplatelets to prevent, reduce, and treat thrombotic complications, such as heart attack, stroke, blood clots, deep vein thrombosis, and pulmonary embolism (ACTIV-4); and

• Evaluate medications previously approved by the FDA for non–COVID-19 indications to reduce the duration and severity of symptoms associated with mild to moderate COVID-19 (ACTIV-6).

For a full list of what is being investigated, visit Combat COVID.

2. ACTIV and ACTIV-associated trials contributed to FDA Emergency Use Authorizations (EUAs) for remdesivir and monoclonal antibodies.

COVID-19 clinical trials are contributing to the development of monoclonal antibody (mAb) treatments and multiple vaccines. Treatment with mAbs have proven to be successful in reducing hospitalization and lessening serious symptoms if administered within the first 10 days of a COVID-19 diagnosis. mAbs also help prevent COVID-19 for those who are immunocompromised or at increased risk for severe COVID-19 progression after exposure to COVID-19. Patients with newly diagnosed COVID-19 may be unaware of mAb treatment options and ongoing clinical trials for COVID-19. Healthcare providers should provide patient education about mAb treatment and an infusion location as soon as possible after a positive COVID-19 for those eligible for the treatments.

Healthcare providers can learn more about mAbs as a treatment option by visiting the Combat COVID Monoclonal Antibody Resources for Clinicians page, which includes a mAb treatment locator tool and information on ordering, administering, billing, and coding.

3. Strong efforts are being made to reach and engage all people in the ACTIV clinical trials.

Inclusive research is essential to ensure that new treatments are effective for persons of all races, ethnicities, sexes, and ages, and for those with preexisting conditions that can affect the course of the disease. COVID-19 has disproportionately affected minority communities with higher COVID-19 infection and hospitalization rates, making diverse participation in clinical trial testing for effective treatments more important than ever.

Healthcare providers play a pivotal role in helping to educate and facilitate the participation of minorities in clinical trials. To date, across the ACTIV clinical trials for COVID-19, participation among Black/African American and/or Hispanic/Latino patients is about 50% of the trial population, with an average of 18% Black/African American and 34% Hispanic/Latino, depending on the trial. Continued broad participation is essential to ensure that approved treatments work for everyone.

4. CombatCOVID.hhs.gov is a one-stop shop for information on the ACTIV and ACTIV-affiliated clinical trials, vaccines, and mAb treatment.

Researchers need the help of patients, their family members, and healthcare providers to enroll volunteer participants in clinical trials. Because hundreds of clinical research sites are participating in the ACTIV clinical trials, thousands of patients are needed to help evaluate proposed treatments. Patients look to their healthcare providers to help them learn about and understand the purpose of the research and to determine which clinical trial may be appropriate for them.

This quick reference decision tree can help you and your patients determine which ACTIV clinical trial may be suitable for them.

5. Healthcare providers and participants are crucial partners with researchers to identify new treatments for COVID-19.

CombatCOVID.hhs.gov and CombateCOVID.hhs.gov (en espanõl) provide up-to-date information in English and Spanish for healthcare providers, patients, and the public about vaccines, mAbs, and ACTIV investigational treatments. Healthcare providers can find:

• Current, accurate information for each ACTIV trial arm as studies are launched and concluded by the NIH;

• Educational resources to download and distribute to patients;

• Treatment guidelines and EUA fact sheets for specific therapies; and

• mAb administration resources.

For assistance with clinical trial enrollment and eligibility questions, healthcare providers and patients can call 1-877-414-8106 or visit the Combat COVID Clinical Trials page. Your patients can reach live help from the call center or via live chat in English and Spanish 24 hours a day, 7 days a week.

United we can Combat COVID. Visit CombatCOVID.hhs.gov to learn more.

Credits:
Lead image: Getty Images
Image 1: Centers for Disease Control and Prevention

Public Information from the CDC and Medscape

Cite this: The ACTIV COVID-19 Clinical Trials: 5 Things to Know - Medscape - Nov 12, 2021.