Clinical Protocol for Convalescent Plasma and Remdesivir Therapy in Nepal

The objective of this compassionate use study is to provide access and evaluate the outcome of Remdesivir and COVID-19 convalescent plasma use in patients with COVID-19. This protocol provides a coordinated approach for distribution and guidance for safe and effective administration of Remdesivir and convalescent plasma with antibodies against SARS CoV-2 for treatment of patients with COVID-19 infection who are most likely to benefit from this investigational treatment and monitor them for the following specific objectives and outcomes:

SPECIFIC OBJECTIVES

1. Provide access to convalescent plasma for hospitalized patients with severe COVID-19 infection (compassionate use, expanded access program)
2. Monitor safety of the therapy with convalescent plasma containing antibodies against SAR CoV-2 and Remdesivir for hospitalized patients with severe COVID-19 infection
3. Evaluate outcomes in patients who received convalescent COVID-19 plasma therapy alone, Remdesivir alone, and both agents.

Study Design: This study will be a prospective, observational clinical study with an intention-to-treat, cross-over design. Comparison groups will be patients who received convalescent plasma vs. those who received Remdesivir. In addition, cross-over to convalescent plasma arm will be allowed for patients who continued to get worse even after receiving Remdesivir for more than 48 hours.

ENROLLMENT Patients will be recruited from all COVID-19 treating hospitals of Nepal which are participating in this clinical study. All hospitalized patients with moderate to severe COVID-19 infection will be screened for Remdesivir Treatment and those with severe to life threatening COVID-19 infection will be screened for Convalescent plasma therapy.

Donors Convalescent plasma donors will be recruited from the record of the hospitals from where they were discharged. The COVID hospitals will be asked to collect names of recovered patients who have voluntarily shown interest to donate plasma. When possible donated plasma will be stored in respective hospitals or blood bank.

Eligibility Criteria:
A. INCLUSION CRITERIA

All patients:

1. Minimum 18 years of age
2. Laboratory-confirmed diagnosis of COVID-19 infection with PCR test positive for SARS-CoV-2
3. Hospitalized patients admitted to an acute care facility for the treatment of COVID-19
4. Signed informed consent provided by the patient or patient's healthcare proxy

   For Remdesivir:
5. Moderate to severe COVID-19 infection who require to be on oxygen supplementation

   For convalescent plasma therapy:

   A patient has to meet one of the following criteria to be eligible for receiving convalescent plasma therapy:
6. Severe or life-threatening COVID-19 infection, or judged by the treating provider to be at high risk of progression to severe or life-threatening disease
7. Patients who progress to severe or life threatening infection despite being on remdesivir for 48 hours or longer.

B. EXCLUSION CRITERIA

1. Under 18 years of age
2. Not confirmed with PCR test for COVID-19 infection
3. Cases not meeting criteria for severe or life-threatening COVID-19 infection
4. Any patient with contraindications for receiving plasma transfusion will not receive plasma
5. Any patient with contraindications for receiving Remdesivir will not receive Remdesivir
6. Patient's declination to enroll in the study