Clinical Trial of Convalescent Plasma Administration as Adjunct Therapy for COVID-19 (Uji Klinik Pemberian Plasma Konvalesen Sebagai Terapi Tambahan COVID-19)

Brief Summary

Detailed Description

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly around the world, with high rates of transmission and substantial mortality. Convalescent plasma (CP) collected from recovered patients has been evaluated in the treatment of SARS, Middle East respiratory syndrome (MERS), and Ebola, but not well further studied and with no definitive results. Preliminary studies in COVID-19 patients showed improvement in clinical status after CP transfusion. However, a multicenter, open-label, randomized clinical trial of 103 patients in China with severe or life-threatening COVID-19 found no statistical difference in clinical improvement within 28 days among patients treated with CP versus standard treatment alone. To date, CP has not been approved as a standard of care for COVID-19. There are insufficient data from well-controlled, adequately powered, randomized clinical trials to evaluate the efficacy and safety of CP for the treatment of this disease. One randomized controlled trial (NCT04342182) was halted for redesign based on the consideration that most COVID-19 patients already have high neutralizing antibody titers at hospital admission and no difference in mortality (p=0.95), hospital stay (p=0.68), or day-15 disease severity (p=0.58) was observed between plasma treated patients and patients on standard of care. Another clinical study (NCT04345523) showed efficacy and safety of CP in preventing progression to severe disease or death. However, this study was halted early due to low enrolment. Further studies have been published and assessed in several systematic reviews that remain uncertain about the safety and effectiveness of CP treatment for COVID-19. The vast majority of studies reporting COVID-19 trials have come from the earlier affected countries with established healthcare systems and better research infrastructure, while very few are from low- and middle-income countries (LMICs). Meanwhile, the cases in LMICs have risen considerably with critical research questions specific to the needs of are hard to answer. As an LMIC with a geographically dispersed archipelago, access to healthcare remains a challenge in remote districts that could impact the adoption of CP deployment in Indonesia. Consequently, clinical trials conducted in LMICs may differ in many respects from those in high-income countries. This study will evaluate the safety and efficacy of CP therapy in hospitalized with moderate and severe COVID-19, to investigate the impacts of the treatment over the course of clinical illness, including non-mortal clinical outcomes. This study will involve hospitals from different places of the Indonesian archipelago, with different characteristics and community structures, social, and values. To obtain supports for the trial, the investigators will seek community engagement that allows investigators and community leaders working collaboratively.

Primary Outcomes

Secondary Outcomes

• Impact of anti-SARS-CoV-2 antibody levels in donors on the efficacy of CP therapy in CP-receiving patients(Days 0, 6, 14, 21, and 28)
• Change in clinical status category in CP-receiving patients(From the initiation of CP treatment until hospital discharge or death, up to 28 days)
• Duration of hospitalization(From admisstion until hospital discharge or death, up to 28 days)
• Duration of mechanical ventilation(From the initiation of CP treatment until hospital discharge or death, up to 28 days)
• Duration of ICU stay(From the initiation of CP treatment until hospital discharge or death, up to 28 days)
• Change in lung image radiography in CP-receiving patients(Days 0, 6, 14, 21, and 28)
• Change in inflammatory parameters in CP-receiving patients(Days 0, 6, 14, 21, and 28)
• Change in coagulation parameters in CP-receiving patients(Days 0, 6, 14, 21, and 28)
• Impact of anti-SARS-CoV-2 antibody levels in donors on the viral clearance in CP-receiving patients(Days 0, 3, 6, 14, 21, and 28)
• Change in viral load in CP-receiving patients(Days 0, 3, 6, 14, 21, and 28)
• Changes in anti-SARS-CoV-2 antibody levels in CP-receiving patients(Days 0, 3, 6, 14, 21, and 28)
• Systemic organ involvement in patients receiving CP treatment(Days 0, 6, 14, 21, and 28)
• Time to resolution of symptoms in patients receiving CP treatment(Days 0, 6, 14, 21, and 28)
• Treatment-related adverse events (AEs) and serious adverse events (SAEs)(From the initiation of CP treatment until hospital discharge or death, up to 28 days)