Observational Study of Convalescent Plasma for Treatment of Veterans With COVID-19

CSP #2030 - Observational Study of Convalescent Plasma for Treatment of Veterans With COVID-19

The purpose of this study is to assess whether convalescent plasma therapy is associated with reduced 30-day all-cause mortality in a population of Veteran inpatients with non-severe coronavirus disease 2019 (COVID-19).

Study Overview

• Status: Completed
• Conditions: Coronavirus Disease 2019 (COVID-19)
• Intervention / Treatment: Biological: COVID-19 convalescent plasma

Detailed Description

The convalescent plasma (CP) of individuals who have recovered from COVID-19 may help reduce symptoms and mortality when given to ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical trials are needed to provide definitive evidence of the benefits and harms of CP in the treatment of COVID-19. While clinical trials are underway, observational research plays a critical role in providing preliminary scientific evidence to guide clinical practice.

This observational study aims to estimate the association between CP therapy and mortality after 30 days in a sample of SARS-CoV-2-positive patients with non-severe illness. Patients include those hospitalized at a facility within the Veterans Health Administration (VHA) of the Department of Veterans Affairs (VA), the largest integrated healthcare system in the United States. Using VA electronic health record data, the study is designed to emulate a target trial of convalescent plasma transfusion and mortality. The primary exposure of interest is the use or non-use of COVID-19 convalescent plasma, and the primary outcome is 30-day all-cause mortality.

A nested trial design will be used, in which patients will be followed from each day in which eligibility criteria are met (while hospitalized and after date of first positive SARS-CoV-2 test) for 30 days. The association between CP therapy and mortality will be assessed using pooled logistic models to estimate 30-day cumulative incidence curves, risk differences, and hazard ratios. Inverse probability weighting derived from propensity scores will be employed to minimize confounding by indication and other biases.

• Study Type: Observational
• Enrollment (Actual): 5044

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02130
      • VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
  • Washington
    • Seattle, Washington, United States, 98108
      • VA Puget Sound Health Care System Seattle Division, Seattle, WA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Veterans with non-severe COVID-19 who tested positive for SARS-CoV-2 infection during admission at a VA medical center or who were admitted as inpatients to a VA medical center within 30 days after a positive test for SARS-CoV-2 infection

Description

Inclusion Criteria:

• US Veterans aged 21-80 years old
• Hospitalized between May 1, 2020 and November 17, 2020 with a SARS-CoV-2 positive test, at a VA Medical Center where convalescent plasma had been administered to at least one patient and remained a current practice at that VA Medical Center
• SARS-CoV-2 positive test within 7 days before or after hospital admission
• Minimum oxygen saturation (measured within the past day) >=90%
• Vitals (pulse, respiration, temperature, systolic blood pressure) and acute labs (hemoglobin, platelet, white blood cells) measured within the past 2 days
• Albumin, Alanine Aminotransferase (ALT), creatinine measured within the past 30 days
• Weight measurement recorded in the past 2 years

Exclusion Criteria:

• Prior intubation, ventilation, high flow oxygen, extracorporeal membrane oxygenation (ECMO), dialysis, or vasopressors during current hospitalization
• Record of prior treatment with CP
• Received long-term care in a domiciliary or nursing home in the past 90 days
• First CP recipient at a site
• Less than 30 days of follow-up

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Exposed; Veterans who received COVID-19 convalescent plasma therapy within 2 days of eligibility	Biological: COVID-19 convalescent plasma; Convalescent plasma collected from individuals who have recovered from COVID-19
Unexposed; Veterans who did not receive COVID-19 convalescent plasma therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause Mortality	Death at 30 days recorded in the electronic health record. Follow-up starts at the treatment date, which must be within 2 days after both hospitalization and SARS-CoV-2-positive test, and ends at 30 days or death.	30 days

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: Mayo Clinic
• Investigators: Study Chair: Nicholas L. Smith, PhD, VA Puget Sound Health Care System Seattle Division, Seattle, WA; Study Chair: Michael J Gaziano, MD MPH, VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Publications and helpful links

General Publications

• Cho K, Keithly SC, Kurgansky KE, Madenci AL, Gerlovin H, Marucci-Wellman H, Doubleday A, Thomas ER, Park Y, Ho YL, Sugimoto JD, Moore KP, Peterson AC, Hoag C, Gupta K, Jeans K, Klote M, Ramoni R, Huang GD, Casas JP, Gagnon DR, Hernan MA, Smith NL, Gaziano JM. Early Convalescent Plasma Therapy and Mortality Among US Veterans Hospitalized With Nonsevere COVID-19: An Observational Analysis Emulating a Target Trial. J Infect Dis. 2021 Sep 17;224(6):967-975. doi: 10.1093/infdis/jiab330.

Helpful Links

• CSP #2030 Study Information

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2020
• Primary Completion (Actual): October 1, 2021
• Study Completion (Actual): October 1, 2021

Study Registration Dates

• First Submitted: September 9, 2020
• First Submitted That Met QC Criteria: September 9, 2020
• First Posted (Actual): September 10, 2020

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: adult; COVID-19; Human; Severe acute respiratory syndrome coronavirus 2; Retrospective Studies; Immunization, Passive; Pandemics; Antibodies, Neutralizing; Antibodies, viral/blood; COVID-19 serotherapy; Coronavirus Infections / therapy
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections
• Other Study ID Numbers: 2030

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data on SARS-CoV-2 testing, COVID-19 treatment, comorbidities, and other COVID-19-related information are available through the VA COVID-19 Shared Data Resource data domain within the VA Corporate Data Warehouse (CDW). Veterans Health Administration (VHA) researchers can request access to VHA data sources and data access tools for a research protocol approved by a VA Research and Development (R&D) Committee and reviewed by an Institutional Review Board (IRB). Information about requesting access to http://vaww.vhadataportal.med.va.gov/DataAccess/ResearchAcces (internal to VA).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No