Clinical trial NCT04570982: Clinical Protocol for Convalescent Plasma and Remdesivir Therapy in Nepal
Official title: Compassionate Use of Remdesivir and Convalescent Plasma Therapy for Treatment of COVID-19 Infection in Nepal : A Prospective Observational Study (Amended Protocol)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: COVID-19
Keywords: Convalescent Plasma
Remdesivir
Lead sponsor: Nepal Health Research Council
Sponsor class: OTHER_GOV
Collaborators: name: Ministry of Health and Population, Nepal
First posted: 2020-09-30
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CROSSOVER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients will be recruited from all COVID-19 treating hospitals of Nepal which are participating in this clinical study.

Brief summary: 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.

Detailed description: 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

Primary outcomes:
measure: Availability of convalescent plasma
timeFrame: 12 Weeks
measure: Amount of Plasma
timeFrame: 12 Weeks
measure: Demographics of recipients
timeFrame: 12 Weeks
measure: Co-morbidity of recipient
timeFrame: 12 Weeks
measure: Donor status
timeFrame: 12 Weeks
measure: Adverse events of convalescent COVID-19 plasma and Remdesivir Therapy
timeFrame: 12 Weeks
measure: Hospital and ICU length of stay
timeFrame: 12 Weeks
measure: Disposition of patients including survival
timeFrame: 12 Weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Birgunj
country: Nepal
facility: Narayani Hospital
city: Dhangadi
country: Nepal
facility: Seti Provincial Hospital
city: Dharān Bāzār
country: Nepal
facility: BP Koirala Institute of Health Sciences (BPKIHS)
city: Kathmandu
country: Nepal
facility: Sukraraj Tropical Disease Hospital
city: Kathmandu
country: Nepal
facility: TU Teaching Hospital
city: Nepalgunj
country: Nepal
facility: Bheri Provincial Hospital
Study officials:
affiliation: Nepal Health Research Council
name: Pradip Gyanwali, MD
role: STUDY_CHAIR
affiliation: Nepal Health Research Council
name: Meghnath Dhimal, PhD
role: STUDY_DIRECTOR
affiliation: Nepal Health Research Council
name: Janak Koirala, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Koirala J, Gyanwali P, Gerzoff RB, Bhattarai S, Nepal B, Manandhar R, Jha R, Sharma S, Sharma YR, Bastola A, Murphy H, Acharya S, Adhikari P, Rajkarnikari M, Vaidya KM, Panthi CL, Bista B, Giri G, Aryal S, Pant S, Pokharel A, Karki S, Basnet S, Koirala B, Dhimal M; Nepal COVID-19 Clinical Study Collaborators. Experience of Treating COVID-19 With Remdesivir and Convalescent Plasma in a Resource-Limited Setting: A Prospective, Observational Study. Open Forum Infect Dis. 2021 Aug 21;8(8):ofab391. doi: 10.1093/ofid/ofab391. eCollection 2021 Aug.