Clinical trial NCT05822583: Strategies and Treatments for Respiratory Infections &Amp; Viral Emergencies (STRIVE): Immune Modulation Strategy Trial
Official title: Strategies and Treatments for Respiratory Infections &Amp; Viral Emergencies (STRIVE): Immune Modulation Strategy Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: COVID-19
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2023-04-21
Enrollment: 1500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 \&gt;2L and \&lt;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 (\&lt;1.0 x 10 9 cells/µL) or lymphopenia (\&lt;1.0 x 10 9 cells/µL)
* Participant has untreated advanced HIV (known CD4 \&lt;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.

Primary outcomes:
measure: Days to Recovery Scale
timeFrame: 60 days post-intervention
Secondary outcomes:
measure: time to sustained recovery though Day 60
timeFrame: baseline to day 60
measure: all-cause mortality though Day 60
timeFrame: baseline to day 60
measure: time to progression
timeFrame: baseline to day 60
measure: Three-category ordinal outcome
timeFrame: Day 60
measure: the pulmonary ordinal outcome
timeFrame: Day 5, 14, and 28
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham University Hospital (Site 213-002)
state: Alabama
city: Tucson
country: United States
facility: Banner University Medical Center Tucson (Site 206-004)
state: Arizona
city: Tucson
country: United States
facility: Southern Arizona VA Healthcare System (Site 074-009)
state: Arizona
city: Davis
country: United States
facility: UC Davis Health (Site 203-004)
state: California
city: Fresno
country: United States
facility: UCSF Fresno (Site 203-005)
state: California
city: Loma Linda
country: United States
facility: VA Loma Linda Healthcare System (074-017)
state: California
city: Long Beach
country: United States
facility: MemorialCare Health System (066-003)
state: California
city: Long Beach
country: United States
facility: VA Long Beach Healthcare System (074-026)
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center (208-002)
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center (Site 203-002)
state: California
city: Mather
country: United States
facility: VA Northern California Health Care System (Site 074-023)
state: California
city: San Diego
country: United States
facility: VA San Diego Healthcare System (074-016)
state: California
city: San Francisco
country: United States
facility: Zuckerberg San Francisco General Hospital and Trauma Center (213-007)
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center at Mount Zion (203-007)
state: California
city: San Francisco
country: United States
facility: San Francisco VAMC (Site 074-002)
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center (Site 203-001)
state: California
city: Stanford
country: United States
facility: Stanford University Hospital & Clinics (Site 203-003)
state: California
city: Aurora
country: United States
facility: Rocky Mountain Regional VA Medical Center (Site 074-010)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital (Site 204-001)
state: Colorado
city: Denver
country: United States
facility: Public Health Institute at Denver Health (Site 017-004)
state: Colorado
city: New Haven
country: United States
facility: Yale University (Site 025-001)
state: Connecticut
city: Washington
country: United States
facility: MedStar Health Research Institute (Site 009-021)
state: District of Columbia
city: Washington
country: United States
facility: Washington DC VA Medical Center (Site 009-004)
state: District of Columbia
city: Tampa
country: United States
facility: Tampa General Hospital (032-001)
state: Florida
city: Atlanta
country: United States
facility: Emory Grady (Site 301-032)
state: Georgia
city: Decatur
country: United States
facility: Hope Clinic, Emory University (Site 301-031)
state: Georgia
city: Chicago
country: United States
facility: University of Illinois at Chicago (008-012)
state: Illinois
city: Fort Wayne
country: United States
facility: Lutheran Medical Group (301-010)
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center (Site 080-044)
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital (202-002)
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center (202-001)
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Hospital and Medical Center (Site 213-001)
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center (Site 201-001)
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Chan Medical School (080-007)
state: Massachusetts
city: Ann Arbor
country: United States
facility: VA Ann Arbor Healthcare System (Site 074-028)
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center (205-001)
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System (014-001)
state: Michigan
city: Detroit
country: United States
facility: Sinai-Grace Hospital (Site 205-005)
state: Michigan
city: Minneapolis
country: United States
facility: M Health Fairview University of Minnesota Medical Center (112-001)
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center (Site 202-005)
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University School of Medicine (Site 003-001)
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center (Site 080-045)
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center (301-024)
state: New Hampshire
city: Camden
country: United States
facility: Cooper University Hospital (019-001)
state: New Jersey
city: Newark
country: United States
facility: New Jersey Medical School Clinical Research Center (028-001)
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Hospital (Site 213-008)
state: New Mexico
city: Bronx
country: United States
facility: Lincoln Medical Center (Site 003-016)
state: New York
city: Bronx
country: United States
facility: James J. Peters VAMC (Site 023-003)
state: New York
city: Brooklyn
country: United States
facility: NYU Brooklyn (301-033)
state: New York
city: Flushing
country: United States
facility: New York Presbyterian Queens (003-005)
state: New York
city: Mineola
country: United States
facility: NYU Long Island (301-034)
state: New York
city: New York
country: United States
facility: New York University Langone Health (301-013)
state: New York
city: New York
country: United States
facility: NYC Health + Hospital Harlem (Site 003-003)
state: New York
city: New York
country: United States
facility: Weill Cornell Clinical Research Unit (065-001)
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center (Site 301-012)
state: New York
city: Durham
country: United States
facility: Duke University Hospital (Site 301-006)
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health (Site 210-001)
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation (Site 207-001)
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University (208-003)
state: Oregon
city: Hershey
country: United States
facility: Penn State Health Milton S. Hershey Medical Center (Site 209-002)
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital (Site 080-036)
state: Rhode Island
city: Providence
country: United States
facility: The Miriam Hospital (Site 080-039)
state: Rhode Island
city: Charleston
country: United States
facility: Ralph H. Johnson VA Medical Center (074-015)
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina (Site 210-002)
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center (Site 212-001)
state: Tennessee
city: Abilene
country: United States
facility: Hendrick Medical Center (Site 080-014)
state: Texas
city: Corpus Christi
country: United States
facility: CHRISTUS Spohn Shoreline Hospital (080-001)
state: Texas
city: Dallas
country: United States
facility: Parkland Health and Hospital Systems (084-002)
state: Texas
city: Dallas
country: United States
facility: Baylor, Scott and White Health (301-003)
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center (084-001)
state: Texas
city: Houston
country: United States
facility: Houston Methodist Research Institute (Site 301-028)
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center (Site 203-006)
state: Texas
city: San Antonio
country: United States
facility: UT Health San Antonio (Site 009-022)
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center (Site 211-001)
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Hospital (211-002)
state: Utah
city: Salem
country: United States
facility: Salem VA Medical Center (Site 074-014)
state: Virginia
city: Seattle
country: United States
facility: Harborview Medical Center (208-001)
state: Washington
city: Spokane
country: United States
facility: Providence (Sacred Heart) (213-004)
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Medicine (Site 301-023)
state: West Virginia
city: Madison
country: United States
facility: William S. Middleton Memorial Veterans Hospital (074-030)
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert Memorial Lutheran Hospital (052-001)
state: Wisconsin
city: Sydney
country: Australia
facility: St. Vincent's Hospital (Site 612-002)
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital (Site 612-058)
state: New South Wales
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital (612-055)
state: Queensland
city: Clayton
country: Australia
facility: Monash Health (612-009)
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health (612-020)
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital (612-017)
state: Victoria
city: Odense
country: Denmark
facility: Odense University Hospital (625-004)
state: C
city: Aalborg
country: Denmark
facility: Aalborg Hospital (Site 625-005)
city: Aarhus
country: Denmark
facility: Aarhus Universitetshospital, Skejby (Site 625-002)
city: Copenhagen
country: Denmark
facility: Rigshospitalet, CHIP (Site 625-006)
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital (Site 625-013)
city: Hellerup
country: Denmark
facility: Herlev/Gentofte Hospital (Site 625-012
city: Hillerød
country: Denmark
facility: Nordsjællands Hospital, Hillerød (Site 625-009)
city: Hvidovre
country: Denmark
facility: Hvidovre University Hospital, Department of Infectious Diseases (Site 625-001)
city: Bordeaux
country: France
facility: Hôpital Saint André (Site 631-041)
city: Tbilisi
country: Georgia
facility: AIDS and Clinical Immunology Research Center (627-201)
city: Cologne
country: Germany
facility: Klinik I für Innere Medizin der Universität zu Köln (622-008)
city: Athens
country: Greece
facility: 1st Respiratory Medicine Department, Athens University Medical School (635-015)
state: Attica
city: Athens
country: Greece
facility: 3rd Dept of Medicine, Medical School, NKUA (635-022)
state: Attica
city: Athens
country: Greece
facility: Attikon University General Hospital (Site 635-009)
state: Attica
city: Alexandroupolis
country: Greece
facility: Democritus University of Thrace (635-021)
state: Evros
city: Chennai
country: India
facility: Chennai Antiviral Research and Treatment Clinical Research Site (Site 612-402)
state: Tamil Nadu
city: Dublin
country: Ireland
facility: St Vincent's University Hospital (Site 634-103)
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital (612-904)
city: Seoul
country: Korea, Republic of
facility: National Medical Center (612-905)
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center (612-901)
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's Hospital (Site 612-903)
city: Seoul
country: Korea, Republic of
facility: Chung-Ang University Hospital (612-902)
city: Abuja
country: Nigeria
facility: Institute of Human Virology-Nigeria (IHVN) (612-601)
state: FCT
city: Warsaw
country: Poland
facility: Wojewodzki Szpital Zakazny (Site 625-302)
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital (Site 612-201)
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol (626-003)
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital del Mar (626-025)
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron (626-033)
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona (626-004)
city: Madrid
country: Spain
facility: Hospital Universitario La Paz (Site 626-012)
city: Stockholm
country: Sweden
facility: Karolinska University Hospital, Solna (Site 625-206)
city: Basel
country: Switzerland
facility: University Hospital Basel (636-004)
city: Bangkok Noi
country: Thailand
facility: Siriraj Hospital (613-002)
state: Bangkok
city: Bangkok
country: Thailand
facility: Chulalongkorn University and The HIV-NAT (Site 613-001)
city: Khon Kaen
country: Thailand
facility: Khon Kaen University, Srinagarind Hospital (613-003)
city: Ivano-Frankivs'k
country: Ukraine
facility: Central City Clinical Hospital of Ivano-Frankivsk City Council (627-302)
city: Kyiv
country: Ukraine
facility: Treatment and Diagnostic Center ADONIS Plus (627-304)
city: Zhytomyr
country: Ukraine
facility: Hospital #1 of Zhytomyr City Council (627-303)
city: Plymouth
country: United Kingdom
facility: University Hospital Plymouth NHS Trust (Site 634-014)
state: Devon
Study officials:
affiliation: University of Minnesota
name: Cavan Reilly, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Christina Barkauskas, MD
role: STUDY_CHAIR
References: