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NCT04355767: C3PO

Convalescent Plasma in Outpatients With COVID-19

Completed Phase 3 Results posted Last updated 19 October 2021
What this trial tests

Phase 3 trial testing Convalescent Plasma in Covid19 in 511 participants. Completed in 29 March 2021.

Timeline
11 August 2020
Primary endpoint
29 March 2021
29 March 2021

Quick facts

Lead sponsorStanford University
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment511
Start date11 August 2020
Primary completion29 March 2021
Estimated completion29 March 2021
Sites53 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Stanford University

Who can join

18 and older, any sex, with Covid19. 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 Patients With Disease Progression (Intention-to-treat Population) Primary · 15 days

Disease progression defined as death or hospital admission or seeking emergency or urgent care within 15 days of randomization.

Patients with a disease-progression event
GroupValue95% CI
Convalescent Plasma77
Placebo81
Hospital admission for any reason
GroupValue95% CI
Convalescent Plasma51
Placebo56
Seeking emergency or urgent care
GroupValue95% CI
Convalescent Plasma25
Placebo25
Death without hospitalization
GroupValue95% CI
Convalescent Plasma1
Placebo0
Number of Patients With Disease Progression (Per-protocol Population) Primary · 15 days

Disease progression defined as death or hospital admission or seeking emergency or urgent care within 15 days of randomization.

Patients with a disease-progression event
GroupValue95% CI
Convalescent Plasma71
Placebo80
Hospital admission for any reason
GroupValue95% CI
Convalescent Plasma47
Placebo55
Seeking emergency or urgent care
GroupValue95% CI
Convalescent Plasma24
Placebo25
Death without hospitalization
GroupValue95% CI
Convalescent Plasma0
Placebo0
Worst Severity Rating on the WHO COVID Ordinal Scale for Clinical Improvement During the 30 Days Following Randomization Secondary · 30 days

This scale was developed by a special World Health Organization (WHO) committee for quantifying COVID-19 illness severity. * 1 = Not hospitalized without limitation in activity (no symptoms) * 2 = Not hospitalized with limitation in activity (continued symptoms) * 3 = Hospitalized not on supplemental oxygen * 4 = Hospitalized on supplemental oxygen by mask or nasal prongs * 5 = Hospitalized on non-invasive ventilation or high flow nasal cannula * 6 = Hospitalized, intubated and mechanically ventilated * 7 = Hospitalized, intubated, mechanically ventilated and requiring additional organ suppor

Severity rating 1
GroupValue95% CI
Convalescent Plasma55
Placebo55
Severity rating 2
GroupValue95% CI
Convalescent Plasma141
Placebo133
Severity rating 3
GroupValue95% CI
Convalescent Plasma12
Placebo17
Severity rating 4
GroupValue95% CI
Convalescent Plasma28
Placebo35
Severity rating 5
GroupValue95% CI
Convalescent Plasma6
Placebo5
Severity rating 6
GroupValue95% CI
Convalescent Plasma1
Placebo0
Severity rating 7
GroupValue95% CI
Convalescent Plasma2
Placebo2
Severity rating 8
GroupValue95% CI
Convalescent Plasma5
Placebo1
Number of Patients With Worsening of Symptoms at Day 15 as a Measure of Time to Disease Progression Secondary · 15 days

Assessed on the COVID Outpatient Ordinal Outcome Scale censored at 15 days after randomization. Scale provides more granular detail for outpatients than the WHO scale (adapted from Harrell and Lindsell, 2020). Worsening of symptoms is defined as any subject admitted to the hospital (level 1), seen in the emergency room (level 2), a patient who reports increased symptoms of 2 levels on the scale over a 24 hour period, or a patient who reports increased symptoms of 1 level observed for a 48 hour period. COVID Outpatient Ordinal Outcomes Scale * 1 = patient requires care in the hospital * 2 = p

GroupValue95% CI
Convalescent Plasma107
Placebo116
Number of Hospital-free Days During the 30 Days Following Randomization Secondary · 30 days
GroupValue95% CI
Convalescent Plasma28.3± 4.9
Placebo28.6± 3.6
All-cause Mortality Secondary · Assessed at 30 days
GroupValue95% CI
Convalescent Plasma5
Placebo1

Adverse events — posted to ClinicalTrials.gov

Time frame: 30 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Convalescent Plasma
Serious: 59/257 (23%)
Deaths: 5/257
Placebo
Serious: 64/254 (25%)
Deaths: 1/254

Serious adverse events (33 terms)

ReactionSystemConvalescent PlasmaPlacebo
PneumoniaInfections and infestations
DyspneaRespiratory, thoracic and mediastinal disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Infusion related reactionInjury, poisoning and procedural complications
Acute respiratory failureRespiratory, thoracic and mediastinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
VomitingGastrointestinal disorders
DehydrationMetabolism and nutrition disorders
AnaemiaBlood and lymphatic system disorders
Atrial fibrillationCardiac disorders
TachycardiaCardiac disorders
Abdominal painGastrointestinal disorders
FatigueGeneral disorders
Influenza like illnessGeneral disorders
Anaphylactic reactionImmune system disorders
Septic shockInfections and infestations
Tooth abscessInfections and infestations
Viral diarrhoeaInfections and infestations
OesophagoscopyInvestigations
HyperglycemiaMetabolism and nutrition disorders
HyperkalaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
EpilepsyNervous system disorders
AnxietyPsychiatric disorders
Psychotic disorderPsychiatric disorders
Other adverse events (36 terms — click to expand)

ReactionSystemConvalescent PlasmaPlacebo
Infusion related reactionInjury, poisoning and procedural complications
DyspneaRespiratory, thoracic and mediastinal disorders
Chest painGeneral disorders
PneumoniaInfections and infestations
VomitingGastrointestinal disorders
MigraineNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Abdominal painGastrointestinal disorders
FatigueGeneral disorders
Coronavirus test positiveInvestigations
DehydrationMetabolism and nutrition disorders
Flank painMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
VertigoEar and labyrinth disorders
DysphagiaGastrointestinal disorders
Infusion site extravasationGeneral disorders
PyrexiaGeneral disorders
NasopharyngitisInfections and infestations
SinusitisInfections and infestations
Alcohol poisoningInjury, poisoning and procedural complications
FallInjury, poisoning and procedural complications
Road traffic accidentInjury, poisoning and procedural complications
Decreased appetiteMetabolism and nutrition disorders
HyperglycemiaMetabolism and nutrition disorders
PresyncopeNervous system disorders
DepressionPsychiatric disorders
ParanoiaPsychiatric disorders
NephrolithiasisRenal and urinary disorders
AsthmaRespiratory, thoracic and mediastinal disorders
BronchospasmRespiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
EcchymosisSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
Tooth extractionSurgical and medical procedures
Venous thrombosis limbVascular disorders

Most-reported serious reactions: Pneumonia, Dyspnea, Hypoxia, Infusion related reaction, Acute respiratory failure, Pulmonary embolism, Vomiting, Dehydration.

Data from ClinicalTrials.gov NCT04355767 adverse events section.

Sponsor's own description

The overarching goal of this project is to confirm or refute the role of passive immunization as a safe and efficacious therapy in preventing the progression from mild to severe/critical COVID-19 illness and to understand the immunologic kinetics of anti-SARS-CoV-2 antibodies after passive immunization.The primary objective is to determine the efficacy and safety of a single dose of convalescent plasma (CP) for preventing the progression from mild to severe COVID-19 illness. The secondary objective is to characterize the immunologic response to CP administration. This study will enroll adults presenting to the emergency department (ED) with mild, symptomatic, laboratory-confirmed COVID-19 illness, who are at high risk for progression to severe/critical illness, but who are clinically stable for outpatient management at randomization.

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. An update on drugs with therapeutic potential for SARS-CoV-2 (COVID-19) treatment.
    Drożdżal S, Rosik J, Lechowicz K, Machaj F, et al · · 2021 · cited 186× · PMID 34991982 · DOI 10.1016/j.drup.2021.100794
  3. Early Convalescent Plasma for High-Risk Outpatients with Covid-19.
    Korley FK, Durkalski-Mauldin V, Yeatts SD, Schulman K, et al · · 2021 · cited 184× · PMID 34407339 · DOI 10.1056/nejmoa2103784
  4. 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
  5. 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
  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

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Trials testing the same drug.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing