VA CoronavirUs Research and Efficacy Studies-1

COVID-19 Clinical Trial

— VACURES-1  

Official title:

VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04539275
• Other study ID #: COVID19-8900-22
• Status: Terminated
• Phase: Phase 3
• Start date: November 16, 2020
• Est. completion date: September 30, 2021

Study information

• Verified date: September 2022
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if treatment with convalescent plasma improves the clinical outcomes of Veterans who are hospitalized and require supplemental oxygen due to COVID-19.

Description:

As of August 25, 2020, SARS-Coronavirus 2 (SARS-CoV-2; COVID-19) infections are approaching 6 million persons and 180,000 deaths in the US. Of the 20% of patients admitted to hospital, up to half progress to ICU admission, respiratory failure or death. Prominent among these progressors are older men, particularly those with underlying comorbidities (e.g., hypertension, diabetes, lung, heart, kidney or liver disease, obesity and immunocompromised), all common among Veterans. There are no drugs or other therapeutics approved by the FDA to prevent or treat COVID-19 infection.

Convalescent plasma therapy is being used empirically, although only five of six small uncontrolled case series (total n=56) in SARS-CoV-23-8 and a recent study with non-randomized controls suggest improved selected clinical, virologic and laboratory outcomes; outcomes in another small randomized trial were equivocal. For other infections, such as influenza and Ebola virus, promising observational studies were not reliably confirmed by controlled trials. In multiple infections, use of convalescent plasma has been distinguished by its safety profile but not by the consistency of its benefit.

The current double-blind, placebo-controlled randomized clinical trial (RCT) is designed to determine definitively whether this intervention is effective in a population at high risk of complications and death from SARS-CoV-2 infection. The investigators compare the effect of convalescent plasma vs. saline placebo with a robust study design, adequate sample size and statistical and logistical rigor to assure that the interventions the investigators make to treat serious disease are well-validated to support its use or to move on to test other potentially safe and effective treatments.

This study is taking place at approximately 25 Veterans Affairs (VA) Medical Centers located across the US. A participant's involvement will last up to 33 days. The entire study, from the date the first person enters until the last participant is seen, is expected to last about 20 months.

Data collected for this study will be analyzed and stored at the Palo Alto Cooperative Studies Program Coordinating Center (CSPCC). After the study is completed, the de-identified, archived data will continue to be stored at the Palo Alto CSPCC, accessible for use by researchers including those outside of the study with an approved Data Use Agreement. The biospecimens collected in the study for current and future research will be kept at the VA Biorepository in Palo Alto, California unless otherwise specified. The biospecimens will be accessible for future research with an approved Sample Use Agreement. The VA Central Institutional Review Board (CIRB) will oversee the biorepository for this study. All samples will be destroyed by standard practice within 20 years of study completion. Sample destruction will be validated according to the Standard Operating Procedures of the VA Biorepository.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 75
• Est. completion date: September 30, 2021
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Veterans must meet all of the following criteria to be eligible to participate:

1. Admitted to a participating VA clinical site with symptoms suggestive of SARS-CoV-2 infection.

2. Participant (or legally authorized representative) provides informed consent prior to initiation of any study procedures.

3. Participant (or legally authorized representative) understands and agrees to comply with planned study procedures.

4. Veteran 18 years of age at time of screening.

5. Has laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or antigen test, as documented by either of the following:

(1)Reverse Transcription polymerase chain reaction (RT-PCR) or antigen positive (nasopharyngeal, oropharyngeal, saliva, lower respiratory) in sample collected 72 hours prior to screening; (2)RT-PCR or antigen positive in sample collected > 72 hours but 168 hours (i.e. 7 days) prior to screening, documented inability to obtain a repeat sample (e.g. due to lack of testing supplies, limited testing capacity, results taking > 24 hours, etc.), AND progressive disease suggestive of ongoing SARS-CoV-2 infection.

6.Requiring oxygen by nasal cannula or by face-mask as a new treatment (or if previously on home oxygen, at a liter flow at least 2 Lpm greater than home prescription), but not on humidified heated high-flow nasal cannula (HHHFNC) at 15 Lpm.

7.Can be randomized within 72 hours of hospital admission. 8.Agrees not to participate in another therapeutic clinical trial for the treatment of COVID-19 or SARS-CoV-2 through Day 29 without approval from the investigator(s). Taking part in other research studies, including those unrelated to SARS-CoV-2, without first discussing it with the investigators of this study may invalidate the results of this study, as well as that of the other study.

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Respiratory failure requiring mechanical ventilation, non-invasive ventilation including continuous positive airway pressure (CPAP) (for an indication other than previously diagnosed sleep apnea and maintained on outpatient settings), or extra-corporeal membrane oxygenation or anticipated to require any of those treatments or to die within 24 hours.

2. Anticipated discharge from the hospital or transfer to another hospital that is not a study site within 72 hours.

3. History of previous transfusion reaction.

4. Previously documented serum immunoglobulin A (IgA) deficiency (<7 mg/dL)

5. Documented to have received convalescent plasma in the last 60 days.

Related Conditions & MeSH terms

• Coronavirus Infections
• COVID-19

Intervention

Drug:
• Convalescent Plasma
Convalescent plasma from persons recovered from SARS-CoV-2 is being used to treat hospitalized individuals with complicated COVID-19 infection.

Other:
• Masked Saline Placebo
0.9% saline solution will be used as the Masked Saline Placebo

Locations

Country	Name	City	State
Puerto Rico	VA Caribbean Healthcare System, San Juan, PR	San Juan
United States	VA Ann Arbor Healthcare System, Ann Arbor, MI	Ann Arbor	Michigan
United States	Rocky Mountain Regional VA Medical Center, Aurora, CO	Aurora	Colorado
United States	Birmingham VA Medical Center, Birmingham, AL	Birmingham	Alabama
United States	James J. Peters VA Medical Center, Bronx, NY	Bronx	New York
United States	Ralph H. Johnson VA Medical Center, Charleston, SC	Charleston	South Carolina
United States	Louis Stokes VA Medical Center, Cleveland, OH	Cleveland	Ohio
United States	VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX	Dallas	Texas
United States	Atlanta VA Medical and Rehab Center, Decatur, GA	Decatur	Georgia
United States	John D. Dingell VA Medical Center, Detroit, MI	Detroit	Michigan
United States	Durham VA Medical Center, Durham, NC	Durham	North Carolina
United States	North Florida/South Georgia Veterans Health System, Gainesville, FL	Gainesville	Florida
United States	Edward Hines Jr. VA Hospital, Hines, IL	Hines	Illinois
United States	Michael E. DeBakey VA Medical Center, Houston, TX	Houston	Texas
United States	William S. Middleton Memorial Veterans Hospital, Madison, WI	Madison	Wisconsin
United States	VA Southern Nevada Healthcare System, North Las Vegas, NV	North Las Vegas	Nevada
United States	Oklahoma City VA Medical Center, Oklahoma City, OK	Oklahoma City	Oklahoma
United States	Orlando VA Medical Center, Orlando, FL	Orlando	Florida
United States	Phoenix VA Health Care System, Phoenix, AZ	Phoenix	Arizona
United States	VA Portland Health Care System, Portland, OR	Portland	Oregon
United States	Hunter Holmes McGuire VA Medical Center, Richmond, VA	Richmond	Virginia
United States	VA Salt Lake City Health Care System, Salt Lake City, UT	Salt Lake City	Utah
United States	South Texas Health Care System, San Antonio, TX	San Antonio	Texas
United States	James A. Haley Veterans' Hospital, Tampa, FL	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Participants Developing Acute Hypoxemic Respiratory Failure or All-cause Death	Respiratory failure is defined as requiring mechanical ventilation, with or without endotracheal intubations, or extra-corporeal membrane oxygenation.	Day 1 through Day 28
Secondary	Time (in Days) to Recovery	Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the Modified World Health Organization (WHO) 8-point Ordinal Scale for Clinical Improvement : 1) Ambulatory, no limitation of activity; 2) Ambulatory, limitation of activity and/or home oxygen; 3) Hospitalized Mild Disease, no oxygen therapy.	Day 1 through Day 28
Secondary	Time (in Days) to Death or Respiratory Failure	Defined as the first day on which the subject died from any cause or had respiratory failure. Respiratory failure is defined by requiring mechanical ventilation, with or without endotracheal intubations, or extra-corporeal membrane oxygenation.	Day 1 through Day 28
Secondary	Proportion of Patients Who Died From Any Cause, Had Respiratory Failure, or Required Humidified Heated High-flow Nasal Cannula (HHHFNC) at >= 15 Lpm	Defined as the proportion of subjects who died from any cause, had respiratory failure, or who required humidified heater high-flow cannula (HHHFNC) at >= 15 Lpm. Respiratory failure is defined by requiring mechanical ventilation, with or without endotracheal intubations, or extra-corporeal membrane oxygenation.	Day 1 through Day 28
Secondary	Time (in Days) to Death, Respiratory Failure, or HHHFNC at >= 15 Lpm	Time to death or respiratory failure is defined as the first day on which the subject died from any cause, had respiratory failure (defined above), or who required HHHFNC at >= 15 Lpm.	Day 1 through Day 28
Secondary	Number of Participants With 28-day All-cause Mortality	Death for Any Reason	Day 1 through Day 28
Secondary	Time to an Improvement of at Least One Category Using an Ordinal Scale	Number of Days until the Modified WHO Clinical Status Improved by at Least One Category; Modified WHO 8-point Ordinal Scale for Clinical Improvement. The scale is as follows: 0) No clinical or Virologic evidence of infection; 1) Ambulatory, no limitation of activity; 2) Ambulatory, limitation of activity and/or home oxygen; 3) Hospitalized Mild Disease, no oxygen therapy; 4) Hospitalized Mild Disease, oxygen by mask or nasal prong; 5a) Hospitalized Severe Disease, humidified high-flow oxygen; 5b) Hospitalized Severe Disease, non-invasive ventilation; 6) Hospitalized Severe Disease, intubation and mechanical ventilation; 7) Hospitalized Severe Disease, ventilation + additional organ support-pressors, renal replacement therapy (RRT), extracorporeal membrane oxygenation (ECMO); 8) Death. The higher the score, the worse the outcome.	Up through 28 days.
Secondary	Time to an Improvement of at Least Two Categories Using an Ordinal Scale	Number of Days until the Modified WHO Clinical Status Improved by at Least Two Categories; Modified WHO 8-point Ordinal Scale for Clinical Improvement. The scale is as follows: 0) No clinical or Virologic evidence of infection; 1) Ambulatory, no limitation of activity; 2) Ambulatory, limitation of activity and/or home oxygen; 3) Hospitalized Mild Disease, no oxygen therapy; 4) Hospitalized Mild Disease, oxygen by mask or nasal prong; 5a) Hospitalized Severe Disease, humidified high-flow oxygen; 5b) Hospitalized Severe Disease, non-invasive ventilation; 6) Hospitalized Severe Disease, intubation and mechanical ventilation; 7) Hospitalized Severe Disease, ventilation + additional organ support-pressors, RRT, ECMO; 8) Death. The higher the score, the worse the outcome.	Up through 28 days.
Secondary	Participant's Clinical Status by Ordinal Scale	Modified WHO 8-point Ordinal Scale for Clinical Improvement. The scale is as follows: 0) No clinical or Virologic evidence of infection; 1) Ambulatory, no limitation of activity; 2) Ambulatory, limitation of activity and/or home oxygen; 3) Hospitalized Mild Disease, no oxygen therapy; 4) Hospitalized Mild Disease, oxygen by mask or nasal prong; 5a) Hospitalized Severe Disease, humidified high-flow oxygen; 5b) Hospitalized Severe Disease, non-invasive ventilation; 6) Hospitalized Severe Disease, intubation and mechanical ventilation; 7) Hospitalized Severe Disease, ventilation + additional organ support-pressors, RRT, ECMO; 8) Death. The higher the score, the worse the outcome.	Days 2, 4, 7, 11, 14, 21, and 28
Secondary	Change in the Ordinal Scale From Baseline to Days 2, 4, 7, 11, 14, 21, and 28	Change in the Modified WHO Clinical Status; Modified WHO 8-point Ordinal Scale for Clinical Improvement. The scale is as follows: 0) No clinical or Virologic evidence of infection; 1) Ambulatory, no limitation of activity; 2) Ambulatory, limitation of activity and/or home oxygen; 3) Hospitalized Mild Disease, no oxygen therapy; 4) Hospitalized Mild Disease, oxygen by mask or nasal prong; 5a) Hospitalized Severe Disease, humidified high-flow oxygen; 5b) Hospitalized Severe Disease, non-invasive ventilation; 6) Hospitalized Severe Disease, intubation and mechanical ventilation; 7) Hospitalized Severe Disease, ventilation + additional organ support-pressors, RRT, ECMO; 8) Death. The higher the score, the worse the outcome.	From Baseline to Days 2, 4, 7, 11, 14, 21, and 28.
Secondary	Categorical Change in the Ordinal Scale From Baseline to Days 2, 4, 7, 11, 14, 21, and 28	Categorical Change in the Modified WHO 8-point Ordinal Scale for Clinical Improvement; Modified WHO 8-point Ordinal Scale for Clinical Improvement. The scale is as follows: 0) No clinical or Virologic evidence of infection; 1) Ambulatory, no limitation of activity; 2) Ambulatory, limitation of activity and/or home oxygen; 3) Hospitalized Mild Disease, no oxygen therapy; 4) Hospitalized Mild Disease, oxygen by mask or nasal prong; 5a) Hospitalized Severe Disease, humidified high-flow oxygen; 5b) Hospitalized Severe Disease, non-invasive ventilation; 6) Hospitalized Severe Disease, intubation and mechanical ventilation; 7) Hospitalized Severe Disease, ventilation + additional organ support-pressors, RRT, ECMO; 8) Death. The higher the score, the worse the outcome.	From Baseline to Days 2, 4, 7, 11, 14, 21, and 28.
Secondary	Time to Discharge or to a National Early Warning Score 2 (NEWS2) of <= 2 Maintained for at Least 22 Hours, Whichever Occurs First	Number of Days until Initial Hospitalization Discharge or (NEWS2 <= 2 Maintained for at Least 22 Hours); The National Early Warning Score 2 (NEWS2) score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters and ranges from 0 to 20. The NEWS2 is being used as an efficacy measure. Higher scores mean a worse outcome.	Up through 28 days.
Secondary	Change in National Early Warning Score 2 (NEWS2) From Day 1 (Baseline) to Days 2, 4, 7, 11, 15, and 29	Change in NEWS2; The National Early Warning Score 2 (NEWS2) has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters and ranges from 0 to 20. The NEWS2 is being used as an efficacy measure. Higher scores mean a worse outcome.	From Day 1 (baseline) to Days 2, 4, 7, 11, 15, and 29
Secondary	Duration of Hospitalization	Number of Days Hospitalized During Initial Hospitalization	Day 1 through Day 28
Secondary	Incidence of Discontinuation or Temporary Suspension of Study Product Administrations (for Any Reason)	Number of participants for whom study product administration was discontinued or temporarily suspended for any reason	Day 1 through Day 3