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Trial record 1 of 1 for:    04488081
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I-SPY COVID-19 TRIAL: An Adaptive Platform Trial for Critically Ill Patients (I-SPY_COVID)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04488081
Recruitment Status : Recruiting
First Posted : July 27, 2020
Last Update Posted : October 10, 2022
Sponsor:
Collaborators:
University of California, San Francisco
University of Pennsylvania
Emory University
University of Alabama at Birmingham
University of Colorado, Denver
University of Southern California
Yale University
Columbia University
Wake Forest University Health Sciences
Sanford Health
Long Beach Memorial Medical Center
Georgetown University
University of California, Davis
Hoag Memorial Hospital Presbyterian
University of Iowa
Main Line Health
Northwestern University
DHR Health Institute for Research and Development
Mercy Hospital Springfield
University of California, Irvine
Spectrum Health Hospitals
Kaiser Permanente
University of Rochester
University of Michigan
West Virginia University
Stamford Hospital
University of Miami
University Hospitals Cleveland Medical Center
Logan Health
Virtua Memorial Hospital Mount Holly
Sanford USD Medical Center
UC Irvine Medical Center
University of Florida Health Shands Hospital
M.D. Anderson Cancer Center
Information provided by (Responsible Party):
QuantumLeap Healthcare Collaborative

Brief Summary:
The goal of this project is to rapidly screen promising agents, in the setting of an adaptive platform trial, for treatment of critically ill COVID-19 patients. In this phase 2 platform design, agents will be identified with a signal suggesting a big impact on reducing mortality and the need for, as well as duration, of mechanical ventilation.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: Remdesivir Drug: Imatinib Mesylate Drug: Dexamethasone Drug: Cenicriviroc Drug: Icatibant Drug: Apremilast Biological: dornase alfa Drug: Celecoxib Drug: Famotidine Biological: IC14 Drug: Aviptadil Biological: narsoplimab Drug: Cyproheptadine Drug: Cyclosporine Phase 2

Detailed Description:

This platform trial will provide access to repurposed and investigational agents for critically ill patients infected with SARS-CoV-2 who have severe or life-threatening COVID-19. The main focus of this trial is a platform study for identifying effective agents for the treatment of COVID-19. Any critically ill patient with known or presumed COVID-19 will be automatically entered into the screening phase of the trial until SARS-CoV-2 infection is confirmed. Basic data will be assembled for each patient (such as ventilatory status and survival). If interested in the therapeutic portion of the trial, potential participants will be asked to sign a consent form describing the backbone treatment and the two specific investigational agent arms to which they may be randomized. The primary endpoints will be time to recover to a durable level 4 (or less) on the WHO COVID-19 ordinal scale for clinical improvement and time to mortality (death). For this trial, a durable level 4 is defined as at least 48 hours at COVID level 4 or less (nasal prongs oxygen) without returning to high flow oxygen or intubation. Acute care facility resource utilization will be automatically calculated (total length of stay in a critical care setting, days intubated, and survival). Any change in status, including intubation, extubation, death or discharge, will be recorded and verified by the attending physician.

Patients will be evaluated based on their initial status (ventilation at entry vs. high flow oxygen). Exploratory biomarkers will be evaluated over time (ARDS phenotypes and other proposed markers) to facilitate clinical learning. A maximum of two investigational arms may be open at a time. The anticipated accrual will be 50 patients per week. The maximum number of participants assigned to an arm without graduation will be 125 patients. Agents can be dropped for futility after enrollment of 40 patients. As the trial proceeds and a better understanding of the underlying mechanisms of the COVID-19 illness emerges, expanded biomarker and data collection can be added as needed to further elucidate how agents are or are not working. The study design features comparison of investigational agent efficacy using a Bayesian design, which will allow the detection of strong efficacy signals with the fewest possible patients. Initially the control will be patients given current standard of care (supportive care for ARDS, including lung protective ventilation and remdesivir and dexamethasone as backbone therapy). As other treatments (for example, anticoagulation) become part of standard supportive care across sites, these will be added to the backbone therapy. If an agent meets the threshold for graduation the company leadership will be informed as will the FDA. The arm with the graduated agent will cease to enroll, allowing a new arm with a different investigational agent to be added. Information about agents disposition will be as follows:

Every trial participant will have blood collected at trial enrollment, day 3, and day 7 for pre-specified biomarker and DNA and RNA analysis. Additional biomarkers can be added as the trial proceeds. Patient outcomes will also be evaluated on the basis of whether patients are ventilated initially or not. All COVID-19 confirmed patients who start high-flow oxygen (WHO COVID-19 level 5; ≥6L oxygen by nasal prongs or mask) will be entered in an Observational Component which will collect data via extraction of medical records.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Platform Trial, Bayesian Design, from 2 arms up to 8 arms
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: I-SPY COVID TRIAL: An Adaptive Platform Trial to Reduce Mortality and Ventilator Requirements for Critically Ill Patients
Actual Study Start Date : July 31, 2020
Estimated Primary Completion Date : July 24, 2023
Estimated Study Completion Date : November 1, 2023


Arm Intervention/treatment
Active Comparator: Control/Backbone (Remdesivir and Dexamethasone)

Participants randomized to the backbone control will be given standard of care (supportive care for ARDS, including remdesivir and, if needed, lung protective ventilation). Because dexamethasone was shown to have benefit in at least one large randomized clinical trial, patients in the backbone control arm should receive dexamethasone for a total of 10 days during the hospitalization or until or hospital discharge.

Remdesivir (intravenous): 200-mg loading dose on day 1, followed by a daily maintenance dose of 100-mg on days 2 through 10.

Dexamethasone (intravenous): 6 mg intravenous or oral dexamethasone once daily up to 10 days or equivalent for alternate corticosteroid if dexamethasone unavailable.

Drug: Remdesivir
Participants who receive remdesivir as part of their standard of care will be administered remdesivir by IV for up to ten days. Remdesivir 200mg loading dose on day 1, followed by 100mg IV once daily maintenance doses for 4 or 9 days.
Other Name: GS-5734

Drug: Dexamethasone
6 mg intravenous of oral dexamethasone once daily up to 10 days or equivalent for alternate corticosteroid if dexamethasone unavailable.

Experimental: Imatinib + Standard of Care
Subjects will be administered standard of care + 800 mg imatinib on Day 1 orally, in divided doses of 400 mg administered twice per day. 400 mg daily will be administered orally for the following 9 days or until discharge, whichever is sooner.
Drug: Remdesivir
Participants who receive remdesivir as part of their standard of care will be administered remdesivir by IV for up to ten days. Remdesivir 200mg loading dose on day 1, followed by 100mg IV once daily maintenance doses for 4 or 9 days.
Other Name: GS-5734

Drug: Imatinib Mesylate
Subjects will be administered 800 mg on Day 1 orally, in divided doses of 400 mg administered twice per day. 400 mg daily will be administered orally for the following 9 days or until discharge, whichever is sooner.

Drug: Dexamethasone
6 mg intravenous of oral dexamethasone once daily up to 10 days or equivalent for alternate corticosteroid if dexamethasone unavailable.

Experimental: Cenicriviroc + Standard of Care (CLOSED)
Subjects administered standard of care + cenicriviroc orally , loading 300 mg qAM followed by 150 mg qPM, 12 hours apart on day 1, then 150 mg BID for total of 14 to 28 days depending on date of hospital discharge.
Drug: Remdesivir
Participants who receive remdesivir as part of their standard of care will be administered remdesivir by IV for up to ten days. Remdesivir 200mg loading dose on day 1, followed by 100mg IV once daily maintenance doses for 4 or 9 days.
Other Name: GS-5734

Drug: Dexamethasone
6 mg intravenous of oral dexamethasone once daily up to 10 days or equivalent for alternate corticosteroid if dexamethasone unavailable.

Drug: Cenicriviroc
Oral, loading 300 mg qAM followed by 150 mg qPM, 12 hours apart on day 1, then 150 mg BID for total of 14 to 28 days depending on date of hospital discharge.

Experimental: Icatibant + Standard of Care (CLOSED)
Subjects administered standard of care + icatibant subcutaneously, a safety run-in for the first 10 subjects was conducted using a regimen of 30 mg q8h × 3 days. All subsequent subjects received drug at 30 mg q8h x 6 days.
Drug: Remdesivir
Participants who receive remdesivir as part of their standard of care will be administered remdesivir by IV for up to ten days. Remdesivir 200mg loading dose on day 1, followed by 100mg IV once daily maintenance doses for 4 or 9 days.
Other Name: GS-5734

Drug: Dexamethasone
6 mg intravenous of oral dexamethasone once daily up to 10 days or equivalent for alternate corticosteroid if dexamethasone unavailable.

Drug: Icatibant
Subcutaneous, a safety run-in for the first 10 subjects was conducted using a regimen of 30 mg q8h × 3 days. All subsequent subjects received drug at 30 mg q8h x 6 days.
Other Name: Firazyr

Experimental: Apremilast + Standard of Care (CLOSED)
Subjects administered standard of care + apremilast orally , 30 mg bid × 14 days.
Drug: Remdesivir
Participants who receive remdesivir as part of their standard of care will be administered remdesivir by IV for up to ten days. Remdesivir 200mg loading dose on day 1, followed by 100mg IV once daily maintenance doses for 4 or 9 days.
Other Name: GS-5734

Drug: Dexamethasone
6 mg intravenous of oral dexamethasone once daily up to 10 days or equivalent for alternate corticosteroid if dexamethasone unavailable.

Drug: Apremilast
oral, 30 mg bid × 14 days.
Other Name: Otezla

Experimental: Dornase + Standard of Care (CLOSED)

For Non-intubated subjects: Subjects administered standard of care + dornase, 2.5 mg BID until hospital discharge, improvement to room air (or baseline oxygen use prior to illness) for 24 hours, or total of 14 days of study drug, whichever comes first.

For intubated subjects: Subjects administered standard of care + dornase, 5.0 mg BID in 10 mL normal saline until extubation or 14 days, whichever comes first. If intubated for less than 14 days, extubated subjects received 2.5 mg BID for a total Dornase treatment of 14 days, or until hospital discharge, whichever comes first.

Drug: Remdesivir
Participants who receive remdesivir as part of their standard of care will be administered remdesivir by IV for up to ten days. Remdesivir 200mg loading dose on day 1, followed by 100mg IV once daily maintenance doses for 4 or 9 days.
Other Name: GS-5734

Drug: Dexamethasone
6 mg intravenous of oral dexamethasone once daily up to 10 days or equivalent for alternate corticosteroid if dexamethasone unavailable.

Biological: dornase alfa

For Non-intubated subjects: 2.5 mg BID until hospital discharge, improvement to room air (or baseline oxygen use prior to illness) for 24 hours, or total of 14 days of study drug, whichever comes first.

For intubated subjects: 5.0 mg BID in 10 mL normal saline until extubation or 14 days, whichever comes first. If intubated for less than 14 days, extubated subjects received 2.5 mg BID for a total Dornase treatment of 14 days, or until hospital discharge, whichever comes first.

Other Name: Pulmozyme

Experimental: Celecoxib/famotidine + Standard of Care (CLOSED)

Subjects administered standard of care + celecoxib/famotidine orally .

Celecoxib, oral: 400 mg BID for 7 days.

Famotidine, oral: High dose 80 mg QID for 7 days followed by 40 mg BID for a course of 14 days.

Drug: Remdesivir
Participants who receive remdesivir as part of their standard of care will be administered remdesivir by IV for up to ten days. Remdesivir 200mg loading dose on day 1, followed by 100mg IV once daily maintenance doses for 4 or 9 days.
Other Name: GS-5734

Drug: Dexamethasone
6 mg intravenous of oral dexamethasone once daily up to 10 days or equivalent for alternate corticosteroid if dexamethasone unavailable.

Drug: Celecoxib
Oral: 400 mg BID for 7 days.
Other Name: celebrex

Drug: Famotidine
Oral: High dose 80 mg QID for 7 days followed by 40 mg BID for a course of 14 days.
Other Name: Pepcid

Experimental: IC14 + Standard of Care (CLOSED)
Subjects administered standard of care + IC14 intravenously , 4 mg/kg on day 1, followed by 2 mg/kg on days 2, 3, 4
Drug: Remdesivir
Participants who receive remdesivir as part of their standard of care will be administered remdesivir by IV for up to ten days. Remdesivir 200mg loading dose on day 1, followed by 100mg IV once daily maintenance doses for 4 or 9 days.
Other Name: GS-5734

Drug: Dexamethasone
6 mg intravenous of oral dexamethasone once daily up to 10 days or equivalent for alternate corticosteroid if dexamethasone unavailable.

Biological: IC14
intravenous, 4 mg/kg on day 1, followed by 2 mg/kg on days 2, 3, 4

Experimental: Narsoplimab + Standard of Care (CLOSED)
Subjects administered standard of care + narsoplimab dosed at 4 mg/kg, given as a 30-minute intravenous infusion (up to a maximum of 370 mg per infusion) twice weekly for a total of four weeks (i.e. 9 doses) or until hospital discharge whichever comes first.
Drug: Remdesivir
Participants who receive remdesivir as part of their standard of care will be administered remdesivir by IV for up to ten days. Remdesivir 200mg loading dose on day 1, followed by 100mg IV once daily maintenance doses for 4 or 9 days.
Other Name: GS-5734

Drug: Dexamethasone
6 mg intravenous of oral dexamethasone once daily up to 10 days or equivalent for alternate corticosteroid if dexamethasone unavailable.

Biological: narsoplimab
Dosed at 4 mg/kg, given as a 30-minute intravenous infusion (up to a maximum of 370 mg per infusion) twice weekly for a total of four weeks (i.e. 9 doses) or until hospital discharge whichever comes first.
Other Name: OMS721

Experimental: Aviptadil + Standard of Care (CLOSED)
Subjects administered standard of care + aviptadil (inhalation via nebulizer), 100 µg three times (TID) daily for a maximum of 14 days
Drug: Remdesivir
Participants who receive remdesivir as part of their standard of care will be administered remdesivir by IV for up to ten days. Remdesivir 200mg loading dose on day 1, followed by 100mg IV once daily maintenance doses for 4 or 9 days.
Other Name: GS-5734

Drug: Dexamethasone
6 mg intravenous of oral dexamethasone once daily up to 10 days or equivalent for alternate corticosteroid if dexamethasone unavailable.

Drug: Aviptadil
Inhalation via nebulizer, 100 µg three times (TID) daily for a maximum of 14 days
Other Name: Zyesami

Experimental: Cyproheptadine + Standard of Care (CLOSED)
Subjects administered standard of care + cyproheptadine via 4 mg tablet, with dosing regimen of 8 mg every 8 hours daily for ten (10) days.
Drug: Remdesivir
Participants who receive remdesivir as part of their standard of care will be administered remdesivir by IV for up to ten days. Remdesivir 200mg loading dose on day 1, followed by 100mg IV once daily maintenance doses for 4 or 9 days.
Other Name: GS-5734

Drug: Dexamethasone
6 mg intravenous of oral dexamethasone once daily up to 10 days or equivalent for alternate corticosteroid if dexamethasone unavailable.

Drug: Cyproheptadine
4 mg tablet, with dosing regimen of 8 mg every 8 hours daily for ten (10) days. If the patient weighs less than 48 kg, the regimen is 6 mg every 8 hours daily for ten (10) days. If the participant was discharged before completion of this dosing regimen the drug was not continued.
Other Name: periactin

Experimental: Cyclosporine + Standard of Care (CLOSED)
Subjects administered standard of care + modified cyclosporine at an oral dose of 5mg/kg per day administered in two divided doses daily for 5-days.
Drug: Remdesivir
Participants who receive remdesivir as part of their standard of care will be administered remdesivir by IV for up to ten days. Remdesivir 200mg loading dose on day 1, followed by 100mg IV once daily maintenance doses for 4 or 9 days.
Other Name: GS-5734

Drug: Dexamethasone
6 mg intravenous of oral dexamethasone once daily up to 10 days or equivalent for alternate corticosteroid if dexamethasone unavailable.

Drug: Cyclosporine
Modified CsA at an oral dose of 5mg/kg per day administered in two divided doses daily for 5-days.
Other Name: CsA




Primary Outcome Measures :
  1. Identify agents that will result in substantial improvements to the clinical condition of participants with severe COVID-19 [ Time Frame: Up to 28 days ]
    Time to achieve durable change in COVID-19 to ordinal level 4 or less for at least 48 hours

  2. Mortality [ Time Frame: Up to 28 days ]
    Time to death


Secondary Outcome Measures :
  1. Improvement in disease severity [ Time Frame: Up to 60 days ]
    % of COVID-19 level 5 who never progress to COVID-19 level 6/7

  2. Health care utilization [ Time Frame: Up to 60 days ]
    Ventilator-free Days

  3. Frequency of serious AEs [ Time Frame: Up to 60 days ]

    Total grade 3 or higher AEs by arm and total number of patients with grade 3 or higher AEs by arm.

    ● Total grade 3 or higher AEs of special interest by arm and total number of patients with grade 3 or higher AEs of special interest by arms (based upon lab assessments)




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

A. Male or Female, at least 18 years old.

B. Admitted to the hospital and placed on high flow oxygen (greater than 6L by nasal cannula or mask delivery system) or intubated for the treatment of (established or presumed) COVID-19.

C. Informed consent provided by the patient or health care proxy.

D. Confirmation of SARS-CoV-2 infection by PCR or Rapid antigen testing for SARS-CoV-2 infection prior to randomization.

Exclusion Criteria:

A. Pregnant or breastfeeding women (must be documented by a pregnancy test during hospitalization)

B. History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent based on review of the medical record and patient history.

C. Comfort measures only.

D. Acute liver disease, or chronic liver disease with a Child-Pugh score greater than 11.

E. Resident for more than six months at a skilled nursing facility.

F. Estimated mortality greater than 50% over the next six months from underlying chronic conditions.

G. Time since requirement for high flow oxygen or ventilation greater than 5 days.

H. Anticipated transfer to another hospital which is not a study site within 72 hours.

I. Patients with either end-stage kidney disease or acute kidney injury who are on dialysis.

J. Co-enrollment in clinical trials of pharmacologic agents requiring an IND

K. On 3 or more vasopressors

L. Pre-existing heart failure with a known left ventricular ejection fraction <25% or unstable angina pectoris


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04488081


Contacts
Layout table for location contacts
Contact: Paul Henderson, PhD 1-925-570-1615 p.henderson@quantumleaphealth.org
Contact: Karyn DiGiorgio, MS 1-415-307-1539 karyn.digiorgio@quantumleaphealth.org

Locations
Show Show 30 study locations
Sponsors and Collaborators
QuantumLeap Healthcare Collaborative
University of California, San Francisco
University of Pennsylvania
Emory University
University of Alabama at Birmingham
University of Colorado, Denver
University of Southern California
Yale University
Columbia University
Wake Forest University Health Sciences
Sanford Health
Long Beach Memorial Medical Center
Georgetown University
University of California, Davis
Hoag Memorial Hospital Presbyterian
University of Iowa
Main Line Health
Northwestern University
DHR Health Institute for Research and Development
Mercy Hospital Springfield
University of California, Irvine
Spectrum Health Hospitals
Kaiser Permanente
University of Rochester
University of Michigan
West Virginia University
Stamford Hospital
University of Miami
University Hospitals Cleveland Medical Center
Logan Health
Virtua Memorial Hospital Mount Holly
Sanford USD Medical Center
UC Irvine Medical Center
University of Florida Health Shands Hospital
M.D. Anderson Cancer Center
Investigators
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Principal Investigator: Carolyn Carolyn, MD University of California, San Francisco
Principal Investigator: Kathleen D Liu, MD University of California, San Francisco
Principal Investigator: Laura Esserman, MD University of California, San Francisco
Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: QuantumLeap Healthcare Collaborative
ClinicalTrials.gov Identifier: NCT04488081    
Other Study ID Numbers: I-SPY-COVID
First Posted: July 27, 2020    Key Record Dates
Last Update Posted: October 10, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: We will share data on a case by case basis with appropriate IRB review and review by our Data Safety Monitoring Comittee.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Post publication or earlier if warranted.
Access Criteria: Sharing criteria are based on the circumstances of the request and whether the data have been published.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by QuantumLeap Healthcare Collaborative:
COVID-19
severe disease
Platform Trial
Acute Respiratory Distress Syndrome
ARDS
SARS-COV-2
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Cyproheptadine
Cyclosporine
Remdesivir
Cenicriviroc
Dexamethasone
Celecoxib
Apremilast
Icatibant
Imatinib Mesylate
Famotidine
Cyclosporins
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids