Clinical trial NCT04373460: Convalescent Plasma to Limit SARS-CoV-2 Associated Complications
Official title: Comparison of the Efficacy and Safety of Human Coronavirus Immune Plasma (HCIP) vs. Control (SARS-CoV-2 Non-immune) Plasma Among Outpatients With Symptomatic COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: SARS-CoV 2
Keywords: COVID-19
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: State of Maryland
name: Bloomberg Philanthropies
name: United States Department of Defense
name: National Institute of Allergy and Infectious Diseases (NIAID)
name: National Center for Advancing Translational Sciences (NCATS)
First posted: 2020-05-04
Enrollment: 1225
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A total of approximately 1344 eligible subjects stratified with a target goal (but not binding) of 50:50 in the \<65 vs ≥ 65 age range will be randomized in a 1:1 ratio to receive either HCIP or control plasma.
Primary purpose: TREATMENT

Brief summary: To assess the efficacy and safety of Human coronavirus immune plasma (HCIP) to reduce the risk of hospitalization or death, the duration of symptoms and duration of nasopharyngeal or oropharyngeal viral shedding.

Detailed description: The purpose of this randomized, double-blind, controlled, phase 2 trial is to evaluate the efficacy of treatment with HCIP in reducing hospitalization and death prior to hospitalization among outpatient adults who have RNA detection test-confirmed COVID-19 AND have developed any symptoms of COVID-19 including but not limited to fever, cough, or other COVID associated symptoms like anosmia. Ambulatory/outpatient adults subjects 18 years of age or older, regardless of risk factors for severe illness may participate. A total of approximately 1344 eligible subjects stratified with a target goal (but not binding) of 50:50 in the \<65 vs ≥ 65 age range will be randomized in a 1:1 ratio to receive either HCIP or control plasma.

Eligibility criteria: Inclusion Criteria:

* ≥ 18 years of age
* Competent and capable to provide informed consent
* • Positive molecular test for presence of SARS-CoV-2 in fluid collected by saliva for antigen, oropharyngeal or nasopharyngeal swab
* Experiencing any symptoms of COVID-19 including but not limited to fever(T\> 100.5º F), cough, or other COVID associated symptoms like anosmia
* ≤ 8 days since the first symptoms of COVID-19
* ≤ 8 days since first positive SARS-CoV-2 RNA test
* Able and willing to comply with protocol requirements listed in the informed consent

Exclusion Criteria:

* Hospitalized or expected to be hospitalized within 24 hours of enrollment
* Psychiatric or cognitive illness or recreational drug/alcohol use that in the opinion of the principal investigator, would affect subject safety and/or compliance
* History of prior reactions to transfusion blood products
* Inability to complete therapy with the study product within 24 hours after enrollment
* Receiving any treatment drug for COVID-19 within 14 days prior to screening evaluation (monoclonal antibodies, compassionate use or study trial related). Steroid treatment at any time does not affect study eligibility

Primary outcomes:
measure: Cumulative Number of Hospitalizations or Deaths Prior to Hospitalization
timeFrame: Up to day 28
measure: Cumulative Incidence of Severe Infusion Reactions
timeFrame: Up to day 28
measure: Cumulative Incidence of Treatment-related Grade 3 or Higher Adverse Events
timeFrame: Up to day 90
measure: Cumulative Incidence of Treatment-related Acute Respiratory Distress Syndrome (ARDS)
timeFrame: Up to day 28
Secondary outcomes:
measure: Serum SARS-CoV-2 Antibody Titers by Visit
timeFrame: Days 0, 14, 28 and 90
Other outcomes:
measure: Number of Participants With ICU Admission
timeFrame: Up to day 90
measure: Number of Participants With Invasive Mechanical Ventilation
timeFrame: Up to day 90
measure: Number of Participants Who Died
timeFrame: Up to day 90
measure: Number of Participants With Resolved COVID-19 Symptoms at Day 14
timeFrame: Day 14
measure: Number of Participants With Resolved COVID-19 Symptoms at Day 28
timeFrame: Day 28
measure: Number of Participants With Resolved COVID-19 Symptoms at Day 90
timeFrame: Day 90
measure: Impact of Convalescent Plasma on Outcome as Assessed by Change in Hospitalization Rate
timeFrame: Day 0 to Day 90
measure: Impact of Donor Antibody Titers on Hospitalization Rate of Convalescent Plasma Recipients
timeFrame: Day 0 to Day28
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Chinle
country: United States
facility: Center for American Indian Health - Chinle Office
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic, Phoenix
state: Arizona
city: Tucson
country: United States
facility: University of Arizona, Phoenix
state: Arizona
city: Tucson
country: United States
facility: University of Arizona, Tuscon
state: Arizona
city: Whiteriver
country: United States
facility: Center for American Indian Health - Whiteriver Office
state: Arizona
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Orange
country: United States
facility: University of California, Irvine Health
state: California
city: Danbury
country: United States
facility: Western Connecticut Health Network, Danbury Hospital
state: Connecticut
city: Norwalk
country: United States
facility: Western Connecticut Health Network, Norwalk Hospital
state: Connecticut
city: Coral Gables
country: United States
facility: University of Miami
state: Florida
city: Miami
country: United States
facility: University of Miami Clinical Translational Research Site
state: Florida
city: Evanston
country: United States
facility: NorthShore University HealthSystem
state: Illinois
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: Annapolis
country: United States
facility: Anne Arundel Medical Center
state: Maryland
city: Baltimore
country: United States
facility: The Johns Hopkins University
state: Maryland
city: Hyattsville
country: United States
facility: MedStar Washington Hospital Center
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts Worcester
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Albuquerque
country: United States
facility: University of New Mexico Health Sciences Center
state: New Mexico
city: Gallup
country: United States
facility: Center for American Indian Health - Gallup Office
state: New Mexico
city: Shiprock
country: United States
facility: Center for American Indian Health - Shiprock Office
state: New Mexico
city: Poughkeepsie
country: United States
facility: Vassar Brothers Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Providence
country: United States
facility: Lifespan/BrownUniversity (Rhode Island Hospital)
state: Rhode Island
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Salt Lake City
country: United States
facility: The University of Utah
state: Utah
Study officials:
affiliation: The Johns Hopkins University
name: David J Sullivan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sullivan DJ, Gebo KA, Shoham S, Bloch EM, Lau B, Shenoy AG, Mosnaim GS, Gniadek TJ, Fukuta Y, Patel B, Heath SL, Levine AC, Meisenberg BR, Spivak ES, Anjan S, Huaman MA, Blair JE, Currier JS, Paxton JH, Gerber JM, Petrini JR, Broderick PB, Rausch W, Cordisco ME, Hammel J, Greenblatt B, Cluzet VC, Cruser D, Oei K, Abinante M, Hammitt LL, Sutcliffe CG, Forthal DN, Zand MS, Cachay ER, Raval JS, Kassaye SG, Foster EC, Roth M, Marshall CE, Yarava A, Lane K, McBee NA, Gawad AL, Karlen N, Singh A, Ford DE, Jabs DA, Appel LJ, Shade DM, Ehrhardt S, Baksh SN, Laeyendecker O, Pekosz A, Klein SL, Casadevall A, Tobian AAR, Hanley DF. Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma. medRxiv [Preprint]. 2021 Dec 21:2021.12.10.21267485. doi: 10.1101/2021.12.10.21267485.
citation: Sullivan DJ, Gebo KA, Shoham S, Bloch EM, Lau B, Shenoy AG, Mosnaim GS, Gniadek TJ, Fukuta Y, Patel B, Heath SL, Levine AC, Meisenberg BR, Spivak ES, Anjan S, Huaman MA, Blair JE, Currier JS, Paxton JH, Gerber JM, Petrini JR, Broderick PB, Rausch W, Cordisco ME, Hammel J, Greenblatt B, Cluzet VC, Cruser D, Oei K, Abinante M, Hammitt LL, Sutcliffe CG, Forthal DN, Zand MS, Cachay ER, Raval JS, Kassaye SG, Foster EC, Roth M, Marshall CE, Yarava A, Lane K, McBee NA, Gawad AL, Karlen N, Singh A, Ford DE, Jabs DA, Appel LJ, Shade DM, Ehrhardt S, Baksh SN, Laeyendecker O, Pekosz A, Klein SL, Casadevall A, Tobian AAR, Hanley DF. Early Outpatient Treatment for Covid-19 with Convalescent Plasma. N Engl J Med. 2022 May 5;386(18):1700-1711. doi: 10.1056/NEJMoa2119657. Epub 2022 Mar 30.