NCT04348656: CONCOR-1

CONvalescent Plasma for Hospitalized Adults With COVID-19 Respiratory Illness (CONCOR-1)

Terminated Phase 3 Results posted Last updated 3 March 2022

What this trial tests

Phase 3 trial testing Convalescent plasma in COVID-19 in 940 participants. Terminated before completion.

Timeline

14 March 2020

Primary endpoint
5 March 2021

16 June 2021

Quick facts

Lead sponsor	Hamilton Health Sciences Corporation
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	940
Start date	14 March 2020
Primary completion	5 March 2021
Estimated completion	16 June 2021
Sites	73 locations across Canada, United States, Brazil

Drugs / interventions tested

• Convalescent plasma — full drug profile →

Conditions studied

• COVID-19 — all drugs for COVID-19 →

Sponsor

Hamilton Health Sciences Corporation — full company profile →

Who can join

16 and older, any sex, with COVID-19. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Who Were Intubated or Died Primary · Day 30

Endpoint of the need for intubation or patient death

Group	Value	95% CI
Convalescent Plasma	199
Standard of Care	86

Time to Intubation or In-hospital Death Secondary · Day 30

Time in days from randomization to occurrence of intubation or death

Group	Value	95% CI
Convalescent Plasma	22.8	± 11.0
Standard of Care	23.4	± 11.0

Ventilator-free Days by Day 30 Secondary · Day 30

Number of days off ventilator at 30 days

Group	Value	95% CI
Convalescent Plasma	23.4	± 10.4
Standard of Care	24.0	± 10.5

Death by Day 30 Secondary · Day 30

Occurrence of patient death at 30 days

Group	Value	95% CI
Convalescent Plasma	141
Standard of Care	63

Length of Stay in Intensive Care Unit (ICU) Secondary · Day 30

Number of days spent in the intensive care unit (ICU) over the 30-day period following randomization

Group	Value	95% CI
Convalescent Plasma	4.3	± 7.9
Standard of Care	3.7	± 7.1

Need for Renal Replacement Therapy Secondary · Day 30

Need for new renal replacement therapy

Group	Value	95% CI
Convalescent Plasma	10
Standard of Care	6

Need for Extracorporeal Membrane Oxygenation (ECMO) Secondary · Day 30

Requirement for extracorporeal membrane oxygenation (ECMO)

Group	Value	95% CI
Convalescent Plasma	0
Standard of Care	1

Development of Myocarditis Secondary · Day 30

New diagnosis of myocarditis

Group	Value	95% CI
Convalescent Plasma	0
Standard of Care	0

In-hospital Death Secondary · Day 90

Occurrence of death while in hospital, censored at 90 days. Patients who were still in hospital at Day 30 were followed until Day 90 to capture in-hospital mortality.

Group	Value	95% CI
Convalescent Plasma	156
Standard of Care	69

Time to In-hospital Death Secondary · Day 90

Time to in-hospital death at 90 days. Patients who were still in hospital at Day 30 were followed until Day 90 to capture in-hospital mortality.

Group	Value	95% CI
Convalescent Plasma	16.3	± 17.1
Standard of Care	14.8	± 16.3

Length of Stay in Hospital Secondary · Day 90

Number of days from randomization to death or hospital discharge. Patients still in hospital at Day 30 were followed until Day 90 to capture death or discharge from hospital.

Group	Value	95% CI
Convalescent Plasma	16.3	± 17.1
Standard of Care	14.8	± 16.3

Number of Participants With Grade 3 and 4 Serious Adverse Events Secondary · Day 30

Number of participants with Grade 3 and 4 (CTCAE v4.0) serious adverse events, and cumulative incidence of Grade 3 and 4 serious adverse events (using MedDRA AE terms)

Group	Value	95% CI
Convalescent Plasma	92
Standard of Care	30

Adverse events — posted to ClinicalTrials.gov

Time frame: AEs: 30 days; any death (in-hospital or otherwise): 30 days. Participants still in hospital at 30 days were followed for 90 days for in-hospital death only (no AE collection and no follow up once discharged past Day 30).. Reporting threshold: 1%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Convalescent Plasma

Serious: 205/614 (33%)

Deaths: 160/625

Standard of Care

Serious: 81/307 (26%)

Deaths: 70/313

Serious adverse events (57 terms)

Reaction	System	Convalescent Plasma	Standard of Care
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	—	—
Hypoxia	Respiratory, thoracic and mediastinal disorders	—	—
Death NOS	General disorders	—	—
Acute kidney injury	Renal and urinary disorders	—	—
Sepsis	Infections and infestations	—	—
Adult respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	—	—
Respiratory, thoracic and mediastinal disorders - Other	Respiratory, thoracic and mediastinal disorders	—	—
Hypotension	Vascular disorders	—	—
Lung infection	Infections and infestations	—	—
Multi-organ failure	General disorders	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—
Thromboembolic event	Vascular disorders	—	—
Aspiration	Respiratory, thoracic and mediastinal disorders	—	—
Asystole	Cardiac disorders	—	—
Intracranial hemorrhage	Nervous system disorders	—	—
Cardiac arrest	Cardiac disorders	—	—
Infections and infestations - Other	Infections and infestations	—	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—	—
Pulmonary edema	Respiratory, thoracic and mediastinal disorders	—	—
Transfusion associated circulatory overload	Respiratory, thoracic and mediastinal disorders	—	—
Anemia	Blood and lymphatic system disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Renal and urinary disorders - Other	Renal and urinary disorders	—	—
Stroke	Nervous system disorders	—	—
Delirium	Psychiatric disorders	—	—

Other adverse events (9 terms — click to expand)

Reaction	System	Convalescent Plasma	Standard of Care
Hypoxia	Respiratory, thoracic and mediastinal disorders	—	—
Lymphocyte count decreased	Investigations	—	—
Anemia	Blood and lymphatic system disorders	—	—
Infections and infestations, other	Infections and infestations	—	—
Hyperglycemia	Metabolism and nutrition disorders	—	—
Hypertension	Vascular disorders	—	—
Hypermagnesemia	Metabolism and nutrition disorders	—	—
Hypophosphatemia	Metabolism and nutrition disorders	—	—
Urinary tract infection	Infections and infestations	—	—

Most-reported serious reactions: Respiratory Failure, Hypoxia, Death NOS, Acute kidney injury, Sepsis, Adult respiratory distress syndrome, Respiratory, thoracic and mediastinal disorders - Other, Hypotension.

Data from ClinicalTrials.gov NCT04348656 adverse events section.

Sponsor's own description

There is currently no treatment available for COVID-19, the acute respiratory illness caused by the novel SAR-CoV-2. Convalescent plasma from patients who have recovered from COVID-19 that contains antibodies to the virus is a potential therapy. On March 25th, 2020, the FDA approved the use of convalescent plasma under the emergency investigational new drug (eIND) category. Randomized trials are needed to determine the efficacy and safety of COVID-19 convalescent plasma for acute COVID-19 infection.

The objective of the CONCOR-1 trial is to determine the efficacy of transfusion of COVID-19 convalescent plasma to adult patients admitted to hospital with COVID-19 infection at decreasing the frequency of in-hospital mortality in patients hospitalized for COVID-19.

It is hypothesized that treating hospitalized COVID-19 patients with convalescent plasma early in their clinical course will reduce the risk of death, and that other outcomes will be improved including risk of intubation, and length of ICU and hospital stay.

This pan-Canadian clinical trial has the potential to improve patient outcomes and reduce the burden on health care resources including reducing the need for ICU beds and ventilators.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial.
   Bégin P, Callum J, Jamula E, Cook R, et al · · 2021 · cited 212× · PMID 34504336 · DOI 10.1038/s41591-021-01488-2
2. Clinical characteristics of 46 pregnant women with a severe acute respiratory syndrome coronavirus 2 infection in Washington State.
   Lokken EM, Walker CL, Delaney S, Kachikis A, et al · · 2020 · cited 149× · PMID 32439389 · DOI 10.1016/j.ajog.2020.05.031
3. Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review.
   Piechotta V, Chai KL, Valk SJ, Doree C, et al · · 2020 · cited 148× · PMID 32648959 · DOI 10.1002/14651858.cd013600.pub2
4. Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a rapid review.
   Valk SJ, Piechotta V, Chai KL, Doree C, et al · · 2020 · cited 126× · PMID 32406927 · DOI 10.1002/14651858.cd013600
5. Waning of SARS-CoV-2 RBD antibodies in longitudinal convalescent plasma samples within 4 months after symptom onset.
   Perreault J, Tremblay T, Fournier MJ, Drouin M, et al · · 2020 · cited 120× · PMID 33001206 · DOI 10.1182/blood.2020008367
6. Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review.
   Piechotta V, Iannizzi C, Chai KL, Valk SJ, et al · · 2021 · cited 106× · PMID 34013969 · DOI 10.1002/14651858.cd013600.pub4
7. Convalescent Plasma Therapy for COVID-19: State of the Art.
   Focosi D, Anderson AO, Tang JW, Tuccori M. · · 2020 · cited 88× · PMID 32792417 · DOI 10.1128/cmr.00072-20
8. COVID-19 Convalescent Plasma and Clinical Trials: Understanding Conflicting Outcomes.
   Focosi D, Franchini M, Pirofski LA, Burnouf T, et al · · 2022 · cited 79× · PMID 35262370 · DOI 10.1128/cmr.00200-21