CONTAIN COVID-19: Convalescent Plasma to Limit COVID-19 Complications in Hospitalized Patients

CONTAIN COVID-19: Convalescent Plasma to Limit Coronavirus Associated Complications: a Randomized Blinded Phase 2 Study Comparing the Efficacy and Safety of Anti-SARS-CoV2 Plasma to Placebo in COVID-19 Hospitalized Patients

This is a randomized, blinded phase 2 trial that will assess the efficacy and safety of anti-SARS-CoV-2 convalescent plasma in hospitalized patients with acute respiratory symptoms requiring oxygen supplementation.

Study Overview

• Status: Completed
• Conditions: COVID-19; Coronavirus Infection; Coronavirus
• Intervention / Treatment: Biological: Convalescent Plasma; Other: Saline solution

Detailed Description

A total of 300 eligible subjects will be randomized in a 1:1 ratio to receive either convalescent plasma (CP) from people who have recovered from COVID-19 containing antibodies to SARS-CoV-2 or a placebo control, Lactated Ringer's Solution (LR) or saline solution (SS). Hospitalized COVID-19 patients aged ≥18 years of age with respiratory symptoms within 3 to 7 days from the onset of illness OR within 3 days of hospitalization will be eligible to participate.

• Study Type: Interventional
• Enrollment (Actual): 941
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School Of Medicine
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Hospital and Clinics
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • New York, New York, United States, 10003
      • NYU Langone Health
  • Texas
    • Edinburg, Texas, United States, 78539
      • University of Texas Rio Grande Valley
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center
    • Tyler, Texas, United States, 75701
      • The University of Texas Health Science Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora St. Luke's Medical Center
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin / Froedtert Memorial Lutheran Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Patients ≥18 years of age
2. Hospitalized with laboratory confirmed COVID-19
3. One or more of the following respiratory signs or symptoms: cough, chest pain, shortness of breath, fever, oxygen saturation ≤ 94%, abnormal CXR/CT imaging)
4. Hospitalized for ≤ 72 hours OR within day 3 to 7 days from first signs of illness
5. On supplemental oxygen, non-invasive ventilation or high-flow oxygen
6. Patients may be on other randomized controlled trials of pharmaceuticals for COVID -19 and patients who meet eligibility criteria will not be excluded on this basis.

Exclusion Criteria

1. Receipt of pooled immunoglobulin in past 30 days
2. Contraindication to transfusion or history of prior reactions to transfusion blood products
3. Invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
4. Volume overload secondary to congestive heart failure or renal failure
5. Unlikely to survive past 72 hours from screening based on the assessment of the investigator
6. Unlikely to be able to assess and follow outcome due to poor functional status

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Convalescent donor plasma	Biological: Convalescent Plasma; SARS-CoV-2 convalescent plasma (1-2 units; ~250-500 mL) with antibodies to SARS-CoV-21 per April 13, 2020 directive by the FDA, obtained from New York Blood Center will be administered to eligible candidate
Placebo Comparator: Lactated ringer's solution or sterile saline solution	Other: Saline solution; Equivalent volume of saline solution (defined as half-,quarter-, or normal saline) will be administered to eligible candidate as a placebo control group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Score on the WHO 11-point Ordinal Scale for Clinical Improvement at 14 Days	Uninfected 0 Uninfected; no viral RNA detected Ambulatory 1 Asymptomatic; viral RNA detected 2 Symptomatic; Independent 3 Symptomatic; assistance needed Hospitalized: Mild disease 4 Hospitalized; no oxygen therapy 5 Hospitalized; oxygen by mask or nasal prongs Hospitalized: Severe disease 6 Hospitalized; oxygen by NIV or High flow 7 Intubation & Mechanical ventilation; pO2/FIO2 >/= 150 or SpO2/FIO2 >/=200 8 Mechanical ventilation pO2/FIO2 < 150 (SpO2/FIO2 <200) or vasopressors 9 Mechanical ventilation pO2/FIO2 < 150 and vasopressors, dialysis or ECMO Death 10 Dead	14 days post-randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Score on the WHO 11-point Ordinal Scale for Clinical Improvement at 28 Days	Uninfected 0 Uninfected; no viral RNA detected Ambulatory 1 Asymptomatic; viral RNA detected 2 Symptomatic; Independent 3 Symptomatic; assistance needed Hospitalized: Mild disease 4 Hospitalized; no oxygen therapy 5 Hospitalized; oxygen by mask or nasal prongs Hospitalized: Severe disease 6 Hospitalized; oxygen by NIV or High flow 7 Intubation & Mechanical ventilation; pO2/FIO2 >/= 150 or SpO2/FIO2 >/=200 8 Mechanical ventilation pO2/FIO2 < 150 (SpO2/FIO2 <200) or vasopressors 9 Mechanical ventilation pO2/FIO2 < 150 and vasopressors, dialysis or ECMO Death 10 Dead	28 days post-randomization

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: The University of Texas Health Science Center, Houston; Albert Einstein College of Medicine; University of Miami; Yale University; National Center for Advancing Translational Sciences (NCATS); The University of Texas Health Science Center at Tyler
• Investigators: Principal Investigator: Mila B Ortigoza, MD, PhD, NYU Langone Health

Publications and helpful links

General Publications

• Ortigoza MB, Yoon H, Goldfeld KS, Troxel AB, Daily JP, Wu Y, Li Y, Wu D, Cobb GF, Baptiste G, O'Keeffe M, Corpuz MO, Ostrosky-Zeichner L, Amin A, Zacharioudakis IM, Jayaweera DT, Wu Y, Philley JV, Devine MS, Desruisseaux MS, Santin AD, Anjan S, Mathew R, Patel B, Nigo M, Upadhyay R, Kupferman T, Dentino AN, Nanchal R, Merlo CA, Hager DN, Chandran K, Lai JR, Rivera J, Bikash CR, Lasso G, Hilbert TP, Paroder M, Asencio AA, Liu M, Petkova E, Bragat A, Shaker R, McPherson DD, Sacco RL, Keller MJ, Grudzen CR, Hochman JS, Pirofski LA; CONTAIN COVID-19 Consortium for the CONTAIN COVID-19 Study Group; Parameswaran L, Corcoran AT, Rohatgi A, Wronska MW, Wu X, Srinivasan R, Deng FM, Filardo TD, Pendse J, Blaser SB, Whyte O, Gallagher JM, Thomas OE, Ramos D, Sturm-Reganato CL, Fong CC, Daus IM, Payoen AG, Chiofolo JT, Friedman MT, Wu DW, Jacobson JL, Schneider JG, Sarwar UN, Wang HE, Huebinger RM, Dronavalli G, Bai Y, Grimes CZ, Eldin KW, Umana VE, Martin JG, Heath TR, Bello FO, Ransford DL, Laurent-Rolle M, Shenoi SV, Akide-Ndunge OB, Thapa B, Peterson JL, Knauf K, Patel SU, Cheney LL, Tormey CA, Hendrickson JE. Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients: A Randomized Clinical Trial. JAMA Intern Med. 2022 Feb 1;182(2):115-126. doi: 10.1001/jamainternmed.2021.6850.

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2020
• Primary Completion (Actual): March 29, 2021
• Study Completion (Actual): December 12, 2022

Study Registration Dates

• First Submitted: April 22, 2020
• First Submitted That Met QC Criteria: April 24, 2020
• First Posted (Actual): April 28, 2020

Study Record Updates

• Last Update Posted (Estimate): January 26, 2023
• Last Update Submitted That Met QC Criteria: January 24, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• 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: 20-00541

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD that underlie the results reported in this article, after deidenficiation (text, tables, figures, and appendices) will be shared.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• IPD Sharing Access Criteria: The investigator who proposed to use the data will have access to the data upon reasonable request. Requests should be directed to Mila.Ortigoza@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No