Strategies and Treatments for Respiratory Infections &Amp; Viral Emergencies (STRIVE): Immune Modulation Strategy Trial
- Registration Number
- NCT05822583
- Lead Sponsor
- University of Minnesota
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1500
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control group Placebo group Placebo group (IV infusion of normal saline) + baseline IM active treatment group abatacept infusion Active treatment group (IV abatacept infusion, 10 mg/kg up to 1750 mg) + baseline IM
- Primary Outcome Measures
Name Time Method Days to Recovery Scale 60 days post-intervention 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.
- Secondary Outcome Measures
Name Time Method time to sustained recovery though Day 60 baseline to 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
all-cause mortality though Day 60 baseline to 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.
time to progression baseline to day 60 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.Three-category ordinal outcome Day 60 assessed at Day 60, with categories "recovered (alive and at home at Day 60)", "alive and not recovered", and dead
the pulmonary ordinal outcome Day 5, 14, and 28 categories defined as:
1. Can independently undertake usual activities with minimal or no symptoms
2. Symptomatic and currently unable to independently undertake usual activities but no need of supplemental oxygen (or not above premorbid requirements)
3. Supplemental oxygen \<4 liters/min (or \<4 liters/min above premorbid requirements)
4. Supplemental oxygen ≥4 liters/min (or ≥4 liters/min above premorbid requirements, but not high-flow oxygen)
5. Non-invasive ventilation or high-flow oxygen
6. Invasive ventilation, extracorporeal membrane oxygenation (ECMO), mechanical circulatory support, or new receipt of renal replacement therapy
7. Death
Trial Locations
- Locations (127)
University of Alabama Birmingham University Hospital (Site 213-002)
🇺🇸Birmingham, Alabama, United States
Banner University Medical Center Tucson (Site 206-004)
🇺🇸Tucson, Arizona, United States
Southern Arizona VA Healthcare System (Site 074-009)
🇺🇸Tucson, Arizona, United States
UC Davis Health (Site 203-004)
🇺🇸Davis, California, United States
UCSF Fresno (Site 203-005)
🇺🇸Fresno, California, United States
VA Loma Linda Healthcare System (074-017)
🇺🇸Loma Linda, California, United States
MemorialCare Health System (066-003)
🇺🇸Long Beach, California, United States
VA Long Beach Healthcare System (074-026)
🇺🇸Long Beach, California, United States
Cedars-Sinai Medical Center (208-002)
🇺🇸Los Angeles, California, United States
Ronald Reagan UCLA Medical Center (Site 203-002)
🇺🇸Los Angeles, California, United States
VA Northern California Health Care System (Site 074-023)
🇺🇸Mather, California, United States
VA San Diego Healthcare System (074-016)
🇺🇸San Diego, California, United States
Zuckerberg San Francisco General Hospital and Trauma Center (213-007)
🇺🇸San Francisco, California, United States
UCSF Medical Center at Mount Zion (203-007)
🇺🇸San Francisco, California, United States
San Francisco VAMC (Site 074-002)
🇺🇸San Francisco, California, United States
UCSF Medical Center (Site 203-001)
🇺🇸San Francisco, California, United States
Stanford University Hospital & Clinics (Site 203-003)
🇺🇸Stanford, California, United States
Rocky Mountain Regional VA Medical Center (Site 074-010)
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital (Site 204-001)
🇺🇸Aurora, Colorado, United States
Public Health Institute at Denver Health (Site 017-004)
🇺🇸Denver, Colorado, United States
Yale University (Site 025-001)
🇺🇸New Haven, Connecticut, United States
MedStar Health Research Institute (Site 009-021)
🇺🇸Washington, District of Columbia, United States
Washington DC VA Medical Center (Site 009-004)
🇺🇸Washington, District of Columbia, United States
Tampa General Hospital (032-001)
🇺🇸Tampa, Florida, United States
Emory Grady (Site 301-032)
🇺🇸Atlanta, Georgia, United States
Hope Clinic, Emory University (Site 301-031)
🇺🇸Decatur, Georgia, United States
University of Illinois at Chicago (008-012)
🇺🇸Chicago, Illinois, United States
Lutheran Medical Group (301-010)
🇺🇸Fort Wayne, Indiana, United States
University of Kansas Medical Center (Site 080-044)
🇺🇸Kansas City, Kansas, United States
Seoul St. Mary's Hospital (Site 612-903)
🇰🇷Seoul, Korea, Republic of
Massachusetts General Hospital (202-002)
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center (202-001)
🇺🇸Boston, Massachusetts, United States
Lahey Hospital and Medical Center (Site 213-001)
🇺🇸Burlington, Massachusetts, United States
Baystate Medical Center (Site 201-001)
🇺🇸Springfield, Massachusetts, United States
University of Massachusetts Chan Medical School (080-007)
🇺🇸Worcester, Massachusetts, United States
VA Ann Arbor Healthcare System (Site 074-028)
🇺🇸Ann Arbor, Michigan, United States
University of Michigan Medical Center (205-001)
🇺🇸Ann Arbor, Michigan, United States
Henry Ford Health System (014-001)
🇺🇸Detroit, Michigan, United States
Sinai-Grace Hospital (Site 205-005)
🇺🇸Detroit, Michigan, United States
M Health Fairview University of Minnesota Medical Center (112-001)
🇺🇸Minneapolis, Minnesota, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University of Mississippi Medical Center (Site 202-005)
🇺🇸Jackson, Mississippi, United States
Washington University School of Medicine (Site 003-001)
🇺🇸Saint Louis, Missouri, United States
University of Nebraska Medical Center (Site 080-045)
🇺🇸Omaha, Nebraska, United States
Dartmouth-Hitchcock Medical Center (301-024)
🇺🇸Lebanon, New Hampshire, United States
Cooper University Hospital (019-001)
🇺🇸Camden, New Jersey, United States
New Jersey Medical School Clinical Research Center (028-001)
🇺🇸Newark, New Jersey, United States
University of New Mexico Hospital (Site 213-008)
🇺🇸Albuquerque, New Mexico, United States
Lincoln Medical Center (Site 003-016)
🇺🇸Bronx, New York, United States
James J. Peters VAMC (Site 023-003)
🇺🇸Bronx, New York, United States
NYU Brooklyn (301-033)
🇺🇸Brooklyn, New York, United States
New York Presbyterian Queens (003-005)
🇺🇸Flushing, New York, United States
NYU Long Island (301-034)
🇺🇸Mineola, New York, United States
New York University Langone Health (301-013)
🇺🇸New York, New York, United States
NYC Health + Hospital Harlem (Site 003-003)
🇺🇸New York, New York, United States
Weill Cornell Clinical Research Unit (065-001)
🇺🇸New York, New York, United States
Mount Sinai Medical Center (Site 301-012)
🇺🇸New York, New York, United States
Duke University Hospital (Site 301-006)
🇺🇸Durham, North Carolina, United States
Wake Forest Baptist Health (Site 210-001)
🇺🇸Winston-Salem, North Carolina, United States
Cleveland Clinic Foundation (Site 207-001)
🇺🇸Cleveland, Ohio, United States
Oregon Health and Science University (208-003)
🇺🇸Portland, Oregon, United States
Penn State Health Milton S. Hershey Medical Center (Site 209-002)
🇺🇸Hershey, Pennsylvania, United States
Rhode Island Hospital (Site 080-036)
🇺🇸Providence, Rhode Island, United States
Chung-Ang University Hospital (612-902)
🇰🇷Seoul, Korea, Republic of
The Miriam Hospital (Site 080-039)
🇺🇸Providence, Rhode Island, United States
Ralph H. Johnson VA Medical Center (074-015)
🇺🇸Charleston, South Carolina, United States
Medical University of South Carolina (Site 210-002)
🇺🇸Charleston, South Carolina, United States
Vanderbilt University Medical Center (Site 212-001)
🇺🇸Nashville, Tennessee, United States
Hendrick Medical Center (Site 080-014)
🇺🇸Abilene, Texas, United States
CHRISTUS Spohn Shoreline Hospital (080-001)
🇺🇸Corpus Christi, Texas, United States
Parkland Health and Hospital Systems (084-002)
🇺🇸Dallas, Texas, United States
Baylor, Scott and White Health (301-003)
🇺🇸Dallas, Texas, United States
UT Southwestern Medical Center (084-001)
🇺🇸Dallas, Texas, United States
Houston Methodist Research Institute (Site 301-028)
🇺🇸Houston, Texas, United States
University of Texas Health Science Center (Site 203-006)
🇺🇸Houston, Texas, United States
UT Health San Antonio (Site 009-022)
🇺🇸San Antonio, Texas, United States
Intermountain Medical Center (Site 211-001)
🇺🇸Murray, Utah, United States
University of Utah Hospital (211-002)
🇺🇸Salt Lake City, Utah, United States
Salem VA Medical Center (Site 074-014)
🇺🇸Salem, Virginia, United States
Harborview Medical Center (208-001)
🇺🇸Seattle, Washington, United States
Providence (Sacred Heart) (213-004)
🇺🇸Spokane, Washington, United States
West Virginia University Medicine (Site 301-023)
🇺🇸Morgantown, West Virginia, United States
William S. Middleton Memorial Veterans Hospital (074-030)
🇺🇸Madison, Wisconsin, United States
Froedtert Memorial Lutheran Hospital (052-001)
🇺🇸Milwaukee, Wisconsin, United States
St. Vincent's Hospital (Site 612-002)
🇦🇺Sydney, New South Wales, Australia
Westmead Hospital (Site 612-058)
🇦🇺Westmead, New South Wales, Australia
Royal Brisbane and Women's Hospital (612-055)
🇦🇺Brisbane, Queensland, Australia
Monash Health (612-009)
🇦🇺Clayton, Victoria, Australia
Austin Health (612-020)
🇦🇺Heidelberg, Victoria, Australia
The Alfred Hospital (612-017)
🇦🇺Melbourne, Victoria, Australia
Odense University Hospital (625-004)
🇩🇰Odense, C, Denmark
Aalborg Hospital (Site 625-005)
🇩🇰Aalborg, Denmark
Aarhus Universitetshospital, Skejby (Site 625-002)
🇩🇰Aarhus, Denmark
Rigshospitalet, CHIP (Site 625-006)
🇩🇰Copenhagen, Denmark
Bispebjerg Hospital (Site 625-013)
🇩🇰Copenhagen, Denmark
Herlev/Gentofte Hospital (Site 625-012
🇩🇰Hellerup, Denmark
Nordsjællands Hospital, Hillerød (Site 625-009)
🇩🇰Hillerød, Denmark
Hvidovre University Hospital, Department of Infectious Diseases (Site 625-001)
🇩🇰Hvidovre, Denmark
Hôpital Saint André (Site 631-041)
🇫🇷Bordeaux, France
AIDS and Clinical Immunology Research Center (627-201)
🇬🇪Tbilisi, Georgia
Klinik I für Innere Medizin der Universität zu Köln (622-008)
🇩🇪Cologne, Germany
1st Respiratory Medicine Department, Athens University Medical School (635-015)
🇬🇷Athens, Attica, Greece
3rd Dept of Medicine, Medical School, NKUA (635-022)
🇬🇷Athens, Attica, Greece
Attikon University General Hospital (Site 635-009)
🇬🇷Athens, Attica, Greece
Democritus University of Thrace (635-021)
🇬🇷Alexandroupolis, Evros, Greece
Chennai Antiviral Research and Treatment Clinical Research Site (Site 612-402)
🇮🇳Chennai, Tamil Nadu, India
St Vincent's University Hospital (Site 634-103)
🇮🇪Dublin, Ireland
Seoul National University Bundang Hospital (612-904)
🇰🇷Seongnam, Korea, Republic of
National Medical Center (612-905)
🇰🇷Seoul, Korea, Republic of
Asan Medical Center (612-901)
🇰🇷Seoul, Korea, Republic of
Institute of Human Virology-Nigeria (IHVN) (612-601)
🇳🇬Abuja, FCT, Nigeria
Wojewodzki Szpital Zakazny (Site 625-302)
🇵🇱Warsaw, Poland
Tan Tock Seng Hospital (Site 612-201)
🇸🇬Singapore, Singapore
Hospital Universitari Germans Trias i Pujol (626-003)
🇪🇸Badalona, Barcelona, Spain
Hospital del Mar (626-025)
🇪🇸Barcelona, Spain
Hospital Universitari Vall d'Hebron (626-033)
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona (626-004)
🇪🇸Barcelona, Spain
Hospital Universitario La Paz (Site 626-012)
🇪🇸Madrid, Spain
Karolinska University Hospital, Solna (Site 625-206)
🇸🇪Stockholm, Sweden
University Hospital Basel (636-004)
🇨🇭Basel, Switzerland
Siriraj Hospital (613-002)
🇹🇭Bangkok Noi, Bangkok, Thailand
Chulalongkorn University and The HIV-NAT (Site 613-001)
🇹🇭Bangkok, Thailand
Khon Kaen University, Srinagarind Hospital (613-003)
🇹🇭Khon Kaen, Thailand
Central City Clinical Hospital of Ivano-Frankivsk City Council (627-302)
🇺🇦Ivano-Frankivs'k, Ukraine
Treatment and Diagnostic Center ADONIS Plus (627-304)
🇺🇦Kyiv, Ukraine
Hospital #1 of Zhytomyr City Council (627-303)
🇺🇦Zhytomyr, Ukraine
University Hospital Plymouth NHS Trust (Site 634-014)
🇬🇧Plymouth, Devon, United Kingdom