Clinical Protocol for Convalescent Plasma and Remdesivir Therapy in Nepal (CPT-R-Nepal)

• ClinicalTrials.gov Identifier: NCT04570982
• Recruitment Status: Unknown
• First Posted: September 30, 2020
• Last Update Posted: September 30, 2020
• Sponsor: Dr. Pradip Gyanwali,MD
• Collaborator: Ministry of Health and Population, Nepal
• Information provided by (Responsible Party): Dr. Pradip Gyanwali,MD, Nepal Health Research Council

Tracking Information

• First Submitted Date: July 24, 2020
• First Posted Date: September 30, 2020
• Last Update Posted Date: September 30, 2020
• Actual Study Start Date: July 30, 2020
• Estimated Primary Completion Date: October 30, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 29, 2020)

• Availability of convalescent plasma [ Time Frame: 12 Weeks ]
  • percentage of donors who donated plasma versus those who were eligible for donation
  • percentage of patient who received plasma vs. requests received
• Amount of Plasma [ Time Frame: 12 Weeks ]
  - amount of plasma administered per patient
• Demographics of recipients [ Time Frame: 12 Weeks ]
  - type of patients receiving plasma therapy : Age in Years, Sex: M/F,
• Co-morbidity of recipient [ Time Frame: 12 Weeks ]
  - recipient comorbidities: Smoking, Diabetes, Heart disease, Chronic lung disease, chronic liver disease, cancer, organ transplant, HIV infection, TB. HIV, HBV, HCV, Syphillis
• Donor status [ Time Frame: 12 Weeks ]
  • donor health status: HIV, HBV, HCV, Syphillis
  • Donor status: duration after recovery from COVID-19, plasma antibody titer against SARS CoV-2
• Adverse events of convalescent COVID-19 plasma and Remdesivir Therapy [ Time Frame: 12 Weeks ]
  • any expected and unexpected adverse events during or after treatment (upto 7 days)
  • any other complications related or unrelated to plasma transfusion and Remdesivir during hospital stay
• Hospital and ICU length of stay [ Time Frame: 12 Weeks ]
  - number of days of hospital stay and ICU stay
• Disposition of patients including survival [ Time Frame: 12 Weeks ]
  - condition at discharge: complete recovery, partial recovery with complications, death

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)

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.

• Study Type: Observational
• Study Design: Observational Model: Case-Crossover; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• 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.
• Condition: COVID-19

Intervention

Biological: Convalescent Plasma

The objective of this protocol is to provide a coordinated approach for distribution and guidance for safe and effective administration of convalescent serum with antibodies against SAR CoV-2 for treatment of patients with COVID-19 infection who are most likely to benefit from this investigational treatment and monitor them.

Study Groups/Cohorts

Convalescent Plasma with SOC

All patients will receive CPT and SOC

Intervention: Biological: Convalescent Plasma

• Publications *: 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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: September 29, 2020): 200
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 30, 2020
• Estimated Primary Completion Date: October 30, 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Nepal

Administrative Information

• NCT Number: NCT04570982
• Other Study ID Numbers: NHRC2020-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Dr. Pradip Gyanwali,MD, Nepal Health Research Council
• Original Responsible Party: Same as current
• Current Study Sponsor: Dr. Pradip Gyanwali,MD
• Original Study Sponsor: Same as current
• Collaborators: Ministry of Health and Population, Nepal

Investigators

• Study Chair: Pradip Gyanwali, MD; Nepal Health Research Council
• Study Director: Meghnath Dhimal, PhD; Nepal Health Research Council
• Principal Investigator: Janak Koirala, MD, MPH; Nepal Health Research Council

• PRS Account: Nepal Health Research Council
• Verification Date: September 2020