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

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.

Timeline

Start

2020-07-31

Primary completion

2028-07-31

Completion

2030-07-31

Outcome

Missed primary endpoint

paper IC14 treatment did not improve time-to-recovery or 28-day mortality in the overall population PMID 40462830 ↗

paper no agent met pre-specified efficacy/graduation endpoints PMID 36883141 ↗

release “Narsoplimab was not observed to shorten the time to recovery in critically ill patients with COVID-19 in this study.” omeros.com ↗

Publications

• Background Files DC, Matthay MA, Calfee CS, Aggarwal NR, Asare AL, Beitler JR, Berger PA, Burnham EL, Cimino G, Coleman MH, Crippa A, Discacciati A, Gandotra S, Gibbs KW, Henderson PT, Ittner CAG, Jauregui A, Khan KT, Koff JL, Lang J, LaRose M, Levitt J, Lu R, McKeehan JD, Meyer NJ, Russell DW, Thomas KW, Eklund M, Esserman LJ, Liu KD; ISPY COVID Adaptive Platform Trial Network; undefined. I-SPY COVID adaptive platform trial for COVID-19 acute respiratory failure: rationale, design and operations. BMJ Open. 2022 Jun 6;12(6):e060664. doi: 10.1136/bmjopen-2021-060664.
• Mabrey FL, Martin TR, Calfee CS, Liu KD, LaCombe B, Brown-Swigart L, Discacciati A, Eklund M, Heckbert SR, Matthay MA, Esserman L, Wurfel MM. Anti-CD14 treatment in patients with severe COVID-19: Clinical and biological effects in a Phase 2 randomized open-label adaptive platform clinical trial. CHEST Crit Care. 2025 Mar;3(1):100117. doi: 10.1016/j.chstcc.2024.100117. Epub 2024 Dec 9.
• Pomponio R, Peterson RA, Owusu M, Slaughter S, Melgar S, Jolley SE, Burnham EL. Phosphatidylethanol measures in patients with severe COVID-19-associated respiratory failure identify a subset with alcohol misuse. Alcohol Clin Exp Res (Hoboken). 2025 Jan;49(1):165-174. doi: 10.1111/acer.15495. Epub 2024 Nov 26.
• I-SPY COVID Consortium. Report of the first seven agents in the I-SPY COVID trial: a phase 2, open label, adaptive platform randomised controlled trial. EClinicalMedicine. 2023 Apr;58:101889. doi: 10.1016/j.eclinm.2023.101889. Epub 2023 Mar 3.
• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Apremilast	Small molecule	30 mg	Oral
Subject	Aviptadil	Peptide	100 ug	Inhaled
Subject	Celecoxib	Other / unclassified	400 mg	Oral
Subject	Cenicriviroc	Small molecule	150 mg	Oral
Subject	Cyclosporine	Peptide	5 mg/kg	Oral
Subject	Cyproheptadine	Small molecule	6 mg	Oral
Subject	Cyproheptadine	Small molecule	8 mg	Oral
Subject	Famotidine	Other / unclassified	40 mg	Oral
Subject	IC14	Monoclonal antibody	2 mg/kg	Intravenous
Subject	Icatibant	Peptide	30 mg	Subcutaneous
Subject	Imatinib	Small molecule	400 mg	Oral
Subject	dornase alfa	Protein / enzyme biologic	2.5 mg	Inhaled
Subject	dornase alfa	Protein / enzyme biologic	5 mg	Inhaled
Subject	narsoplimab	Monoclonal antibody	4 mg/kg	Intravenous
Background	Dexamethasone	Small molecule	6 mg	Intravenous
Background	Remdesivir	Small molecule	100 mg	Intravenous

Indications