I-SPY COVID-19 TRIAL: An Adaptive Platform Trial for Critically Ill Patients

Conditions

• COVID-19

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Remdesivir — DRUG
  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.
• Imatinib Mesylate — DRUG
  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.
• Dexamethasone — DRUG
  6 mg intravenous of oral dexamethasone once daily up to 10 days or equivalent for alternate corticosteroid if dexamethasone unavailable.
• Cenicriviroc — DRUG
  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.
• Icatibant — DRUG
  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.
• Apremilast — DRUG
  oral, 30 mg bid × 14 days.
• dornase alfa — BIOLOGICAL
  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.
• Celecoxib — DRUG
  Oral: 400 mg BID for 7 days.
• Famotidine — DRUG
  Oral: High dose 80 mg QID for 7 days followed by 40 mg BID for a course of 14 days.
• IC14 — BIOLOGICAL
  intravenous, 4 mg/kg on day 1, followed by 2 mg/kg on days 2, 3, 4
• Aviptadil — DRUG
  Inhalation via nebulizer, 100 µg three times (TID) daily for a maximum of 14 days
• narsoplimab — BIOLOGICAL
  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.
• Cyproheptadine — DRUG
  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.
• Cyclosporine — DRUG
  Modified CsA at an oral dose of 5mg/kg per day administered in two divided doses daily for 5-days.

Study Details

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.

Key Dates

First listed

Jul 27, 2020

Start date

Jul 31, 2020

Status verified

Mar 2026

Primary completion

Jul 31, 2028

Completion

Jul 31, 2030

Study Design

Enrollment

1,500 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Active Comparator: Control/Backbone - Remdesivir and Dexamethasone (CLOSED)
  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.
• Experimental: Imatinib + Standard of Care (CLOSED)
  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.
• 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.
• 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.
• Experimental: Apremilast + Standard of Care (CLOSED)
  Subjects administered standard of care + apremilast orally , 30 mg bid × 14 days.
• 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.
• 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.
• 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
• 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.
• 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
• 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.
• 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.
• Experimental: Imatinib (PENDING ACTIVATION)
  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.

Primary Outcome Measure

Identify agents that will result in substantial improvements to the clinical condition of participants with COVID-19. [ Time Frame: Up to 28 days ]

Locations (36)

Find similar trials in Birmingham, AL

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