Strategies and Treatments for Respiratory Infections &Amp; Viral Emergencies (STRIVE): Immune Modulation Strategy Trial

COVID-19 can trigger a dysregulated immune response, and previous studies have shown that immune modulation can improve outcomes in hospitalized patients. This trial is designed to determine whether intensification of immune modulation early in the course of the disease (while patients are on low flow oxygen) with abatacept (active arm) combined with standard of care (SOC) improves recovery as compared with placebo + SOC (placebo arm). For both groups, intensification of immunomodulation will be provided as part of SOC in case of signs of disease progression (patient requires high flow nasal oxygen (HFNO) or more support) and/or if the patient has rapidly increasing oxygen requirement.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: abatacept infusion; Drug: Placebo group

• Study Type: Interventional
• Enrollment (Actual): 285
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2010
      • St. Vincent's Hospital (Site 612-002)
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital (Site 612-058)
  • Queensland
    • Brisbane, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital (612-055)
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health (612-009)
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health (612-020)
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital (612-017)
• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg Hospital (Site 625-005)
  • Aarhus, Denmark, 8200
    • Aarhus Universitetshospital, Skejby (Site 625-002)
  • Copenhagen, Denmark, 2100
    • Rigshospitalet, CHIP (Site 625-006)
  • Copenhagen, Denmark, 2400
    • Bispebjerg Hospital (Site 625-013)
  • Hellerup, Denmark, 2900
    • Herlev/Gentofte Hospital (Site 625-012
  • Hillerød, Denmark, 3400
    • Nordsjællands Hospital, Hillerød (Site 625-009)
  • Hvidovre, Denmark, 2650
    • Hvidovre University Hospital, Department of Infectious Diseases (Site 625-001)
  • C
    • Odense, C, Denmark, 5000
      • Odense University Hospital (625-004)
• France
  • Bordeaux, France, 33000
    • Hôpital Saint André (Site 631-041)
• Georgia
  • Tbilisi, Georgia, 0159
    • AIDS and Clinical Immunology Research Center (627-201)
• Germany
  • Cologne, Germany, 50937
    • Klinik I fur Innere Medizin der Universitat zu Koln (622-008)
• Greece
  • Attica
    • Athens, Attica, Greece, 11527
      • 1st Respiratory Medicine Department, Athens University Medical School (635-015)
    • Athens, Attica, Greece, 11527
      • 3rd Dept of Medicine, Medical School, NKUA (635-022)
    • Athens, Attica, Greece, 12462
      • Attikon University General Hospital (Site 635-009)
  • Evros
    • Alexandroupoli, Evros, Greece, 68131
      • Democritus University of Thrace (635-021)
• India
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600113
      • Chennai Antiviral Research and Treatment Clinical Research Site (Site 612-402)
• Ireland
  • Dublin, Ireland, D04 T6F4
    • St Vincent's University Hospital (Site 634-103)
• Nigeria
  • Federal Capital Territory
    • Abuja, Federal Capital Territory, Nigeria
      • Institute of Human Virology-Nigeria (IHVN) (612-601)
• Poland
  • Warsaw, Poland, 01-201
    • Wojewodzki Szpital Zakazny (Site 625-302)
• Singapore
  • Singapore, Singapore, 308433
    • Tan Tock Seng Hospital (Site 612-201)
• South Korea
  • Seongnam, South Korea, 13620
    • Seoul National University Bundang Hospital (612-904)
  • Seoul, South Korea, 04564
    • National Medical Center (612-905)
  • Seoul, South Korea, 05505
    • Asan Medical Center (612-901)
  • Seoul, South Korea, 06591
    • Seoul St. Mary's Hospital (Site 612-903)
  • Seoul, South Korea, 06973
    • Chung-Ang University Hospital (612-902)
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar (626-025)
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron (626-033)
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona (626-004)
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz (Site 626-012)
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol (626-003)
• Sweden
  • Stockholm, Sweden, 171 76
    • Karolinska University Hospital, Solna (Site 625-206)
• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel (636-004)
• Thailand
  • Bangkok, Thailand, 10330
    • Chulalongkorn University and The HIV-NAT (Site 613-001)
  • Khon Kaen, Thailand, 40002
    • Khon Kaen University, Srinagarind Hospital (613-003)
  • Bangkok
    • Bangkok Noi, Bangkok, Thailand, 10700
      • Siriraj Hospital (613-002)
• Ukraine
  • Ivano-Frankivsk, Ukraine, 76018
    • Central City Clinical Hospital of Ivano-Frankivsk City Council (627-302)
  • Kyiv, Ukraine, 02002
    • Treatment and Diagnostic Center ADONIS Plus (627-304)
  • Zhytomyr, Ukraine, 10002
    • Hospital #1 of Zhytomyr City Council (627-303)
• United Kingdom
  • Devon
    • Plymouth, Devon, United Kingdom, PL6 8DH
      • University Hospital Plymouth NHS Trust (Site 634-014)
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama Birmingham University Hospital (Site 213-002)
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Banner University Medical Center Tucson (Site 206-004)
    • Tucson, Arizona, United States, 85723
      • Southern Arizona VA Healthcare System (Site 074-009)
  • California
    • Davis, California, United States, 95616
      • UC Davis Health (Site 203-004)
    • Fresno, California, United States, 93721
      • UCSF Fresno (Site 203-005)
    • Loma Linda, California, United States, 92357
      • VA Loma Linda Healthcare System (074-017)
    • Long Beach, California, United States, 90806
      • MemorialCare Health System (066-003)
    • Long Beach, California, United States, 90822
      • VA Long Beach Healthcare System (074-026)
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center (208-002)
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center (Site 203-002)
    • Mather, California, United States, 95655
      • VA Northern California Health Care System (Site 074-023)
    • San Diego, California, United States, 92161
      • VA San Diego Healthcare System (074-016)
    • San Francisco, California, United States, 94110
      • Zuckerberg San Francisco General Hospital and Trauma Center (213-007)
    • San Francisco, California, United States, 94115
      • UCSF Medical Center at Mount Zion (203-007)
    • San Francisco, California, United States, 94121
      • San Francisco VAMC (Site 074-002)
    • San Francisco, California, United States, 94143
      • UCSF Medical Center (Site 203-001)
    • Stanford, California, United States, 94305
      • Stanford University Hospital & Clinics (Site 203-003)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Rocky Mountain Regional VA Medical Center (Site 074-010)
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital (Site 204-001)
    • Denver, Colorado, United States, 80204
      • Public Health Institute at Denver Health (Site 017-004)
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University (Site 025-001)
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • MedStar Health Research Institute (Site 009-021)
    • Washington D.C., District of Columbia, United States, 20422
      • Washington DC VA Medical Center (Site 009-004)
  • Florida
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital (032-001)
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Emory Grady (Site 301-032)
    • Decatur, Georgia, United States, 30030
      • Hope Clinic, Emory University (Site 301-031)
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago (008-012)
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Lutheran Medical Group (301-010)
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center (Site 080-044)
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital (202-002)
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center (202-001)
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital and Medical Center (Site 213-001)
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center (Site 201-001)
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Chan Medical School (080-007)
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • VA Ann Arbor Healthcare System (Site 074-028)
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Medical Center (205-001)
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System (014-001)
    • Detroit, Michigan, United States, 48235
      • Sinai-Grace Hospital (Site 205-005)
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • M Health Fairview University of Minnesota Medical Center (112-001)
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center (Site 202-005)
  • Missouri
    • St Louis, Missouri, United States, 63310
      • Washington University School of Medicine (Site 003-001)
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center (Site 080-045)
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center (301-024)
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper University Hospital (019-001)
    • Newark, New Jersey, United States, 07103
      • New Jersey Medical School Clinical Research Center (028-001)
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Hospital (Site 213-008)
  • New York
    • Brooklyn, New York, United States, 11220
      • NYU Brooklyn (301-033)
    • Flushing, New York, United States, 11355
      • New York Presbyterian Queens (003-005)
    • Mineola, New York, United States, 11501
      • NYU Long Island (301-034)
    • New York, New York, United States, 10016
      • New York University Langone Health (301-013)
    • New York, New York, United States, 10037
      • NYC Health + Hospital Harlem (Site 003-003)
    • New York, New York, United States, 10065
      • Weill Cornell Clinical Research Unit (065-001)
    • New York, New York, United States, 11234
      • Mount Sinai Medical Center (Site 301-012)
    • The Bronx, New York, United States, 10451
      • Lincoln Medical Center (Site 003-016)
    • The Bronx, New York, United States, 10468
      • James J. Peters VAMC (Site 023-003)
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Hospital (Site 301-006)
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health (Site 210-001)
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation (Site 207-001)
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University (208-003)
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Health Milton S. Hershey Medical Center (Site 209-002)
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital (Site 080-036)
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hospital (Site 080-039)
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Ralph H. Johnson VA Medical Center (074-015)
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina (Site 210-002)
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center (Site 212-001)
  • Texas
    • Abilene, Texas, United States, 79602
      • Hendrick Medical Center (Site 080-014)
    • Corpus Christi, Texas, United States, 78404
      • CHRISTUS Spohn Shoreline Hospital (080-001)
    • Dallas, Texas, United States, 75235
      • Parkland Health and Hospital Systems (084-002)
    • Dallas, Texas, United States, 75246
      • Baylor, Scott and White Health (301-003)
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center (084-001)
    • Houston, Texas, United States, 77030
      • Houston Methodist Research Institute (Site 301-028)
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center (Site 203-006)
    • San Antonio, Texas, United States, 78229
      • UT Health San Antonio (Site 009-022)
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center (Site 211-001)
    • Salt Lake City, Utah, United States, 84108
      • University of Utah Hospital (211-002)
  • Virginia
    • Salem, Virginia, United States, 24153
      • Salem VA Medical Center (Site 074-014)
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center (208-001)
    • Spokane, Washington, United States, 99204
      • Providence (Sacred Heart) (213-004)
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Medicine (Site 301-023)
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • William S. Middleton Memorial Veterans Hospital (074-030)
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Memorial Lutheran Hospital (052-001)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmation of SARS-CoV2 infection by nucleic acid test (NAT) or equivalent non-NAT test [list of approved tests in the PIM] within 14 days of randomization.
• Requiring hospitalization for the management of COVID-19
• Has evidence of COVID-19 pneumonia (PNA) defined as either receiving supplementary oxygen ≤2L of low flow oxygen with evidence of airspace disease on chest imaging (X ray, computer tomography or ultrasound) OR receiving supplementary oxygen >2L and <10 L of low flow oxygen.
• Currently receiving or planned to receive (ordered) one IM drug (for example, a corticosteroid or baricitinib) as part of treatment of COVID-19 prior to randomization.
• Has started supplemental oxygen for the treatment of COVID-19 within the past 5 calendar days. Patients on home oxygen are eligible if current oxygen flow rate is increased from baseline and other above criteria are met.
• Investigator agrees that the pneumonia is due to COVID-19.

Exclusion Criteria:

• Oxygen requirement of ≥10L or more of low flow oxygen (or equivalent if using Venturi mask, etc), or requiring either HFNO, NIV, IMV, or ECMO.
• Participant has received more than one baseline IM for treatment of the current COVID-19 infection at time of trial enrollment. (Examples: corticosteroid, baricitinib, tocilizumab, anakinra, abatacept, or infliximab.)
• Participant anticipated to not meet all inclusion criteria within 24 hours of randomization in the opinion of the investigator.
• Allergy to investigational agent.
• Neutropenia (absolute neutrophil count <1000 cells/μL) (<1.0 x 10 3 /μL or <1.0 G/L) on most recent lab within 2 calendar days of randomization.
• Lymphopenia (absolute lymphocyte count <200 cells/μL) (<0.20 x 10 3 /μL or <0.20 G/L) on most recent lab within 2 calendar days of randomization.
• Known or suspected active or recent serious infection (bacterial, fungal, viral, or parasitic infection, excepting SARS-CoV-2) that in the opinion of the investigator could constitute a risk when taking investigational agent. Note: Broad spectrum empiric antibiotic usage does not exclude participation.
• Known or suspected history of untreated tuberculosis (TB). TB diagnosis may be suspected based on medical history and concomitant therapies that would suggest TB infection. Participants are also excluded if they have known, latent TB treated for less than 4 weeks with appropriate anti-tuberculosis therapy per local guidelines (by history only, no screening required).
• Have received any live vaccine (or live attenuated) within 3 months before screening or intend to receive a live vaccine (or live attenuated) during the trial. Use of prior non-live (inactivated) vaccinations is allowed for all participants, including any vaccine for COVID-19.
• Pre-existing immunomodulation or immunosuppression that meets any of the following: Participant has received abatacept for an indication other than COVID- 19 within 5 half-lives (65 days) of enrollment (Abatacept elimination half-life is 13.1 days.) Participant is receiving immune modulatory therapy for autoimmune, transplant management or another indication AND has one or more of the following: evidence of active infection (other than COVID-19) or has required reduction in their immune modulatory therapy in the preceding 6 months due to infectious complication (routine reduction as SOC is not an exclusion) or has required intensification in immunotherapy within the preceding 6 months due to organ rejection/worsening underlying disease status (e.g., intensification with an additional agent on top of usual immunosuppressive regimen)
• Participant has recently received or is anticipated to require immune modulatory agents for their underlying disease including chemotherapeutic treatments likely to induce neutropenia (<1.0 x 10 9 cells/µL) or lymphopenia (<1.0 x 10 9 cells/µL)
• Participant has untreated advanced HIV (known CD4 <200 in the past 6 months) AND is not established on antiretroviral therapy
• Pregnancy
• Breastfeeding
• Co-enrollment in other trials not predetermined to be compatible with this trial.
• In the investigator's judgment, the patient has any advanced organ dysfunction that would not make participation appropriate.
• The treating clinician expects inability to participate in trial procedures or participation would not be in the best interests of the patient.

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
Experimental: active treatment group; Active treatment group (IV abatacept infusion, 10 mg/kg up to 1750 mg) + baseline IM	Drug: abatacept infusion; The dose of abatacept will be 10 mg/kg given as a single infusion on Day 0, with a maximum dose of 1,750 mg, so any participant with weight of >175 kg will receive a dose of 1750 mg. + baseline IM (immune modulator)
Placebo Comparator: Control group; Placebo group (IV infusion of normal saline) + baseline IM	Drug: Placebo group; Placebo group (IV infusion of normal saline) + baseline IM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days to Recovery Scale	DRS-60 is a version of the STRIVE clinical recovery scale (CRS) which combines time to recovery with non-recovered clinical state and death to an ordinal outcome.0 indicates best results, 60 represents recovered on Day 60, with not recovered by Day 60 coded as 61 and death (worst outcome) as 62.	60 days post-intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
time to sustained recovery though Day 60	Time to sustained recovery is defined as being discharged from the index hospitalization, followed by being alive and home for 14 consecutive days prior to the end of follow-up	baseline to day 60
all-cause mortality though Day 60	substantial attempts will be made to determine vital status through the end of follow-up by a combined approach of follow-up visits with the participant or proxy, chart review, and review of other available information sources.	baseline to day 60
time to progression	will be defined by the study day on which a participant experiences a definite progression. Definite progression is defined as a participant requiring HFNO, NIV, IMV, or ECMO therapy, OR, if HFNO is unavailable, a participant requiring ≥15 L/min conventional oxygen. Probable progression is defined as a participant not meeting criteria for definite progression but requiring ≥10 L/min conventional oxygen, OR, a participant with an oxygen requirement that has increased by ≥4 L/min in the preceding 24 hours.	baseline to day 60
Three-category ordinal outcome	assessed at Day 60, with categories "recovered (alive and at home at Day 60)", "alive and not recovered", and dead	Day 60
the pulmonary ordinal outcome	categories defined as: Can independently undertake usual activities with minimal or no symptoms; Symptomatic and currently unable to independently undertake usual activities but no need of supplemental oxygen (or not above premorbid requirements); Supplemental oxygen <4 liters/min (or <4 liters/min above premorbid requirements); Supplemental oxygen ≥4 liters/min (or ≥4 liters/min above premorbid requirements, but not high-flow oxygen); Non-invasive ventilation or high-flow oxygen; Invasive ventilation, extracorporeal membrane oxygenation (ECMO), mechanical circulatory support, or new receipt of renal replacement therapy; Death	Day 5, 14, and 28

Collaborators and Investigators

• Sponsor: University of Minnesota
• Investigators: Principal Investigator: Cavan Reilly, PhD, University of Minnesota; Study Chair: Christina Barkauskas, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2023
• Primary Completion (Actual): June 21, 2025
• Study Completion (Actual): August 11, 2025

Study Registration Dates

• First Submitted: February 4, 2023
• First Submitted That Met QC Criteria: April 18, 2023
• First Posted (Actual): April 21, 2023

Study Record Updates

• Last Update Posted (Estimated): September 4, 2025
• Last Update Submitted That Met QC Criteria: August 27, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Abatacept
• Other Study ID Numbers: STRIVE (Alias Study Number)

Drug and device information, study documents

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