Clinical Trial of a Novel Therapeutic with Critically Ill Patients during a Pandemic

COVID-19 is a highly contagious and potentially deadly infectious disease caused by a novel coronavirus (SARS–CoV-2).¹ Presentation of this respiratory disease ranges from asymptomatic or mild symptoms to severe or critical symptoms requiring hospitalization and life-sustaining support.² Prior to the discovery and introduction of effective COVID-19 vaccines, most infections presented in moderate to severe categories and were associated with high levels of morbidity and mortality, especially in older individuals and those with certain co-occurring conditions. The COVID-19 pandemic imposed unique challenges for researchers conducting clinical trials, causing many trials to be put on hold to minimize risks to participants and direct research resources toward the COVID-19 response.

A diverse group of clinical researchers from various specialties including internal medicine, infectious diseases, and intensive care in a Southeast Asian country received a research grant from a foreign sponsor. The study aimed to conduct an open-label, randomized controlled clinical trial to investigate the efficacy and safety of a novel drug compared to the standard therapy for severe COVID-19-induced pneumonia in intensive care settings. A repurposed drug used to treat other diseases showed promise against SARS-CoV-2 based on studies in cells and animals. The researchers hypothesized that patients treated with this novel drug would have better survival outcomes and improved quality of life after COVID-19. Participants would be monitored closely for any drug-related deaths or other adverse events.

The study aimed to recruit 30 patients from the hospital where the study clinicians saw patients. To be eligible for the study, adult patients were required to have PCR-confirmed COVID-19 and be under treatment in the intensive care unit (ICU). After obtaining informed consent, the researcher participants were randomized to receive either the new drug or standard treatment for 7 days. The study was open-label, meaning participants and researchers knew who received which treatment. Safety and efficacy data were collected at defined timepoints. It was anticipated that some participants might need ventilator support for breathing during the trial. In cases in which a participant was incapable of making an independent decision (i.e., due to underlying medical condition and incapacity), the participant’s next-of kin was to be assigned as surrogate decision-maker for research participation.

The researchers decided not to provide participants with compensation for trial participation, based on the reasoning that participants were under intensive care. All blood work and imaging procedures performed during study participation were considered part of routine care in the ICU. The research participants were followed for 4 months to assess survival and safety outcomes. No continuity of treatment or follow-up care was offered to participants after then.