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PETAL Network and COVID-19

The PETAL Network has redirected its entire efforts to COVID-19. Here is an update of our work to find treatments for COVID-19.

Completed studies:

  1. The Network’s first study funded by the NHLBI was a randomized placebo-controlled trial of hydroxychloroquine named ORCHID. The study stopped after enrolling 479 participants was stopped in June 2020 based on the fourth scheduled interim analysis showing no evidence of benefit or harm. ORCHID was published in the Journal of the American Medical Association JAMA. 2020;324(21):2165-76 and the study rationale and methods were published in the Annals of the American Thoracic Society. Data from this study is now available through NHLBI’s BioLINCC.

  2. The RED CORAL study is an NHLBI funded study was launched soon after ORCHID and is now complete. RED CORAL was an observational study of retrospective review of data collected on hospitalized patients with COVID-19. The primary manuscript in under review. Two substudies have been published (give citations for Kusum’s and Papers (two total)

Ongoing studies:

BLUE CORAL is an NHLBI funded multicenter prospective observational study designed to collect comprehensive data on hospitalized patients with COVID-19 is actively enrolling subjects. This study is gathering imaging, biospecimens, and long-term outcomes.

Collaboration studies with other groups:

In response to the global COVID-19 pandemic, the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private initiative was organized by NIH and the Foundation for the NIH (FNIH). ACTIV developed an international strategy for an integrated research response to COVID-19. The strategy involves streamlining human clinical trials, tapping into existing trial networks such as the NHLBIs Prevention and Early treatment of Acute Lung Injury (PETAL) network, coordinating regulatory processes, and prioritization of therapeutic and vaccine candidates. The following studies are funded by the NIH.


    ACTIV-3 is a global multi-center randomized placebo-controlled study of antiviral treatments in patients hospitalized with COVID-19. ACTIV-3 was launched in August 2020 and is still recruiting, after evaluating several agents through its master protocol design. This study has been published in the New England Journal.


    ACTIV-3b, otherwise known as TESICO, is a master protocol similar in structure to ACTIV-3 designed to evaluate safety and efficacy of investigational agents aimed at improving outcomes for patients with acute respiratory failure related to COVID-19. Patients with respiratory failure, which in COVID-19 is likely best termed Acute Respiratory Distress Syndrome (ARDS), have extremely high morbidity and mortality. TESICO began recruitment in April 2021 and is lead by PETAL’s Dr. Sam Brown of Intermountain Medical Center.

  3. ACTIV-4a

    ACTIV-4a is a multi-center clinical trial looking at agents that decreases coagulation of the blood in patients hospitalized for COVID-19. Many patients hospitalized with COVID-19 develop blood clots and signs of coagulation in multiple organs in autopsy findings. These signs of increase coagulation correlate with worse organ failure and mortality. The PETAL Network is collaborating with several other networks nationally and internationally to determine the effectiveness of antithrombotic strategies for prevention of adverse outcomes and organ failure in COVID-19 positive inpatients.

  4. ACTIV-4 Host Tissue

    ACTIV-4 Host Tissue is a multi-center clinical trial testing agents that target the host-tissue response to SARS-CoV-2 infection. The initial agents on the platform will target the Renin-Angiotensin-Aldosterone System (RAAS). The goal of this platform is to determine if these host-tissue targeted agents hasten recovery and prevent illness progression in patients hospitalized with COVID-19.