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

• Sponsor: NYU Langone Health (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04364737
• Collaborator: National Center for Advancing Translational Science (NCATS) (NIH), Albert Einstein College of Medicine (Other), Yale University (Other), The University of Texas Health Science Center, Houston (Other), The University of Texas Health Science Center at Tyler (Other), University of Miami (Other)
• Enrollment: 941
• Locations: 9
• Arms: 2
• Anticipated Duration (Months): 32.5
• Patients Per Site: 104.6
• Patients Per Site Per Month: 3.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19; Coronavirus; Coronavirus Infection	Biological: Convalescent Plasma; Other: Saline solution	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 941 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Apr 17, 2020
• Actual Primary Completion Date: Mar 29, 2021
• Anticipated Study Completion Date: Dec 31, 2022

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Score on the WHO 11-point Ordinal Scale for Clinical Improvement at 14 Days [14 days post-randomization]

   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

Secondary Outcome Measures

1. Score on the WHO 11-point Ordinal Scale for Clinical Improvement at 28 Days [28 days post-randomization]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale University School of Medicine	New Haven	Connecticut	United States	06520
2	University of Miami Hospital and Clinics	Miami	Florida	United States	33136
3	Montefiore Medical Center	Bronx	New York	United States	10467
4	NYU Langone Health	New York	New York	United States	10003
5	University of Texas Rio Grande Valley	Edinburg	Texas	United States	78539
6	The University of Texas Health Science Center	Houston	Texas	United States	77030
7	The University of Texas Health Science Center	Tyler	Texas	United States	75701
8	Aurora St. Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
9	Medical College of Wisconsin / Froedtert Memorial Lutheran Hospital	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• NYU Langone Health
• National Center for Advancing Translational Science (NCATS)
• Albert Einstein College of Medicine
• Yale University
• The University of Texas Health Science Center, Houston
• The University of Texas Health Science Center at Tyler
• University of Miami

Investigators

• Principal Investigator: Mila B Ortigoza, MD, PhD, NYU Langone Health

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 11, 2021
• Informed Consent Form - Feb 28, 2021

More Information

Publications

None provided.

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT04364737
• Other Study ID Numbers: 20-00541
• First Posted: Apr 28, 2020
• Last Update Posted: Apr 1, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: COVID-19; Coronavirus Infections

Study Results

Participant Flow

Arm/Group Title	Convalescent Donor Plasma	Lactated Ringer's Solution or Sterile Saline Solution
Arm/Group Description	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	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.
Period Title: Overall Study
STARTED	468	473
COMPLETED	463	463
NOT COMPLETED	5	10

Baseline Characteristics

Arm/Group Title	Convalescent Donor Plasma	Lactated Ringer's Solution or Sterile Saline Solution	Total
Arm/Group Description	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	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.	Total of all reporting groups
Overall Participants	463	463	926
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.4 (15.2)	63.3 (15.1)	62.35 (15.15)
Sex: Female, Male (Count of Participants)
Female	184 39.7%	197 42.5%	381 41.1%
Male	279 60.3%	266 57.5%	545 58.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	181 39.1%	186 40.2%	367 39.6%
Not Hispanic or Latino	282 60.9%	277 59.8%	559 60.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	41 8.9%	30 6.5%	71 7.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	71 15.3%	68 14.7%	139 15%
White	256 55.3%	278 60%	534 57.7%
More than one race	76 16.4%	70 15.1%	146 15.8%
Unknown or Not Reported	19 4.1%	17 3.7%	36 3.9%
Region of Enrollment (participants) [Number]
United States	463 100%	463 100%	926 100%

Outcome Measures

1. Primary Outcome

Title	Score on the WHO 11-point Ordinal Scale for Clinical Improvement at 14 Days
Description	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
Time Frame	14 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Convalescent Donor Plasma	Lactated Ringer's Solution or Sterile Saline Solution
Arm/Group Description	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	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.
Measure Participants	463	463
Median (Inter-Quartile Range) [score on a scale]	2	2

2. Secondary Outcome

Title	Score on the WHO 11-point Ordinal Scale for Clinical Improvement at 28 Days
Description	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
Time Frame	28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Convalescent Donor Plasma	Lactated Ringer's Solution or Sterile Saline Solution
Arm/Group Description	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	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.
Measure Participants	462	462
Median (Inter-Quartile Range) [score on a scale]	2	2

Adverse Events

Time Frame	90 days from baseline
Adverse Event Reporting Description	Regular investigator assessment at baseline, days 1, 3, 7, 14, 28, 60, and 90.
Arm/Group Title	Convalescent Donor Plasma		Lactated Ringer's Solution or Sterile Saline Solution
Arm/Group Description	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		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.
All Cause Mortality
	Convalescent Donor Plasma		Lactated Ringer's Solution or Sterile Saline Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/468 (0.9%)		3/473 (0.6%)
Serious Adverse Events
	Convalescent Donor Plasma		Lactated Ringer's Solution or Sterile Saline Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	112/468 (23.9%)		108/473 (22.8%)
Blood and lymphatic system disorders
Anaemia	9/468 (1.9%)		8/473 (1.7%)
Thrombocytopenia	3/468 (0.6%)		0/473 (0%)
Cardiac disorders
Atrial fibrillation	14/468 (3%)		7/473 (1.5%)
Bradycardia	0/468 (0%)		2/473 (0.4%)
Cardiac arrest	61/468 (13%)		70/473 (14.8%)
Supraventricular tachycardia	5/468 (1.1%)		7/473 (1.5%)
Ventricular fibrillation	2/468 (0.4%)		0/473 (0%)
Ventricular tachycardia	2/468 (0.4%)		0/473 (0%)
Gastrointestinal disorders
Abdominal wall haematoma	2/468 (0.4%)		0/473 (0%)
Gastrointestinal haemorrhage	11/468 (2.4%)		4/473 (0.8%)
Upper gastrointestinal haemorrhage	0/468 (0%)		2/473 (0.4%)
General disorders
Chest pain	4/468 (0.9%)		3/473 (0.6%)
Death	4/468 (0.9%)		3/473 (0.6%)
Multiple organ dysfunction syndrome	9/468 (1.9%)		7/473 (1.5%)
Hepatobiliary disorders
Cholecystitis	0/468 (0%)		2/473 (0.4%)
Infections and infestations
Bacteraemia	3/468 (0.6%)		11/473 (2.3%)
Candida pneumonia	0/468 (0%)		2/473 (0.4%)
Cytomegalovirus viraemia	2/468 (0.4%)		2/473 (0.4%)
Fungaemia	2/468 (0.4%)		0/473 (0%)
Pneumonia	3/468 (0.6%)		0/473 (0%)
Pneumonia bacterial	15/468 (3.2%)		24/473 (5.1%)
Pneumonia klebsiella	2/468 (0.4%)		3/473 (0.6%)
Pneumonia pseudomonal	4/468 (0.9%)		0/473 (0%)
Pneumonia staphylococcal	0/468 (0%)		4/473 (0.8%)
Sepsis	0/468 (0%)		5/473 (1.1%)
Staphylococcal bacteraemia	3/468 (0.6%)		3/473 (0.6%)
Systemic candida	2/468 (0.4%)		6/473 (1.3%)
Urinary tract infection	7/468 (1.5%)		11/473 (2.3%)
Injury, poisoning and procedural complications
Fall	3/468 (0.6%)		0/473 (0%)
Investigations
Coronavirus test positive	0/468 (0%)		2/473 (0.4%)
Fibrin D dimer increased	4/468 (0.9%)		8/473 (1.7%)
Hepatic enzyme increased	5/468 (1.1%)		3/473 (0.6%)
Liver function test increased	3/468 (0.6%)		4/473 (0.8%)
Nervous system disorders
Cerebral infarction	0/468 (0%)		3/473 (0.6%)
Cerebrovascular accident	2/468 (0.4%)		0/473 (0%)
Embolic stroke	2/468 (0.4%)		0/473 (0%)
Haemorrhagic stroke	0/468 (0%)		2/473 (0.4%)
Intensive care unit acquired weakness	0/468 (0%)		2/473 (0.4%)
Renal and urinary disorders
Acute kidney injury	16/468 (3.4%)		19/473 (4%)
Haematuria	2/468 (0.4%)		0/473 (0%)
Nephrolithiasis	0/468 (0%)		2/473 (0.4%)
Renal failure	17/468 (3.6%)		23/473 (4.9%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	2/468 (0.4%)		0/473 (0%)
Dyspnoea	3/468 (0.6%)		3/473 (0.6%)
Epistaxis	0/468 (0%)		3/473 (0.6%)
Hypoxia	69/468 (14.7%)		56/473 (11.8%)
Pleural effusion	2/468 (0.4%)		0/473 (0%)
Pneumomediastinum	5/468 (1.1%)		2/473 (0.4%)
Pneumothorax	10/468 (2.1%)		9/473 (1.9%)
Pulmonary embolism	10/468 (2.1%)		8/473 (1.7%)
Respiratory distress	13/468 (2.8%)		11/473 (2.3%)
Respiratory failure	65/468 (13.9%)		76/473 (16.1%)
Skin and subcutaneous tissue disorders
Subcutaneous emphysema	0/468 (0%)		2/473 (0.4%)
Surgical and medical procedures
Hospice care	11/468 (2.4%)		12/473 (2.5%)
Hospitalisation	2/468 (0.4%)		0/473 (0%)
Lung assist device therapy	2/468 (0.4%)		0/473 (0%)
Tracheostomy	4/468 (0.9%)		4/473 (0.8%)
Vascular disorders
Deep vein thrombosis	12/468 (2.6%)		6/473 (1.3%)
Haematoma	0/468 (0%)		4/473 (0.8%)
Haemorrhage	0/468 (0%)		2/473 (0.4%)
Hypotension	38/468 (8.1%)		55/473 (11.6%)
Pulmonary haemorrhage	2/468 (0.4%)		0/473 (0%)
Retroperitoneal haematoma	0/468 (0%)		2/473 (0.4%)
Other (Not Including Serious) Adverse Events
	Convalescent Donor Plasma		Lactated Ringer's Solution or Sterile Saline Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	147/468 (31.4%)		136/473 (28.8%)
Blood and lymphatic system disorders
Anaemia	10/468 (2.1%)		8/473 (1.7%)
Leukocytosis	3/468 (0.6%)		5/473 (1.1%)
Cardiac disorders
Atrial fibrillation	12/468 (2.6%)		7/473 (1.5%)
Cardiac arrest	2/468 (0.4%)		0/473 (0%)
Supraventricular tachycardia	0/468 (0%)		2/473 (0.4%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	3/468 (0.6%)		2/473 (0.4%)
General disorders
Pyrexia	4/468 (0.9%)		5/473 (1.1%)
Infections and infestations
Bacteraemia	2/468 (0.4%)		2/473 (0.4%)
Clostridium difficile colitis	2/468 (0.4%)		0/473 (0%)
Cellulitis	0/468 (0%)		2/473 (0.4%)
Enterococcal bacteraemia	2/468 (0.4%)		0/473 (0%)
Oral candidiasis	2/468 (0.4%)		2/473 (0.4%)
Pneumonia	0/468 (0%)		2/473 (0.4%)
Pneumonia bacterial	4/468 (0.9%)		2/473 (0.4%)
Pneumonia klebsiella	2/468 (0.4%)		0/473 (0%)
Urinary tract infection	6/468 (1.3%)		4/473 (0.8%)
Injury, poisoning and procedural complications
Transfusion reaction	3/468 (0.6%)		0/473 (0%)
Investigations
Alanine aminotransferase increased	0/468 (0%)		3/473 (0.6%)
Aspartate aminotransferase increase	0/468 (0%)		2/473 (0.4%)
C-reactive protein increased	0/468 (0%)		2/473 (0.4%)
Fibrin D dimer increased	4/468 (0.9%)		3/473 (0.6%)
Hepatic enzyme increased	8/468 (1.7%)		4/473 (0.8%)
Liver function test increased	10/468 (2.1%)		11/473 (2.3%)
Transaminases increased	0/468 (0%)		2/473 (0.4%)
Troponin increased	0/468 (0%)		4/473 (0.8%)
Troponin T increased	2/468 (0.4%)		0/473 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	0/468 (0%)		3/473 (0.6%)
Hyperkalaemia	0/468 (0%)		3/473 (0.6%)
Hyponatraemia	0/468 (0%)		2/473 (0.4%)
Pregnancy, puerperium and perinatal conditions
Delivery	2/468 (0.4%)		0/473 (0%)
Renal and urinary disorders
Acute kidney injury	23/468 (4.9%)		16/473 (3.4%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	2/468 (0.4%)		3/473 (0.6%)
Hypoxia	11/468 (2.4%)		10/473 (2.1%)
Pneumomediastinum	0/468 (0%)		2/473 (0.4%)
Pneumothorax	2/468 (0.4%)		0/473 (0%)
Respiratory distress	2/468 (0.4%)		3/473 (0.6%)
Respiratory failure	5/468 (1.1%)		4/473 (0.8%)
Skin and subcutaneous tissue disorders
Decubitus ulcer	0/468 (0%)		2/473 (0.4%)
Vascular disorders
Deep vein thrombosis	9/468 (1.9%)		8/473 (1.7%)
Haematoma	2/468 (0.4%)		0/473 (0%)
Hypotension	8/468 (1.7%)		6/473 (1.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.