Study To antagOnize Plasminogen Activator Inhibitor-1 in Severe COVID-19
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|ClinicalTrials.gov Identifier: NCT04634799|
Recruitment Status : Recruiting
First Posted : November 18, 2020
Last Update Posted : January 22, 2021
|Condition or disease||Intervention/treatment||Phase|
|Covid19||Drug: TM5614 Other: Placebo||Phase 1 Phase 2|
This project will evaluate the efficacy and safety of a novel small molecule therapy targeting PAI-1 (TM5614) for patients with severe COVID-19. This is a randomized (1:1), double-blinded trial that will enroll adult patients (> 65 years OR <65 years with at least one major cardiometabolic comorbidity [diabetes, hypertension, or cardiovascular disease]) with COVID-19 requiring supplemental oxygen. The study intervention will be a small molecule inhibitor of PAI-1, TM5614, up to 180 mg, compared to matching placebo for up to 7 days.
Research blood samples for PAI-1 and C-reactive protein (CRP) will be collected at time of enrollment, 48 hours after 1st dose of medication and at day 7 or discharge, whichever comes first.
These objectives will allow for the planning of subsequent phase 3 study, and strengthen implementation of a multi-center randomized trial should this study confirm safety, and suggest efficacy of therapy.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Masking Description:||double-blind, randomized (1:1)|
|Official Title:||Study To antagOnize Plasminogen Activator Inhibitor-1 in Severe COVID-19 (STOP Severe COVID-19)|
|Actual Study Start Date :||January 8, 2021|
|Estimated Primary Completion Date :||November 30, 2021|
|Estimated Study Completion Date :||June 30, 2022|
Active Comparator: TM5614
TM5614 30 mg tablets. 6 tablets (180 mg) taken by mouth, once daily for up to 7 days
TM5614 is provided in 30 mg tablets and 6 tablets (180 mg) will be taken in the evening for up to 7 days.
Other Name: Plasminogen activator inhibitor-1 (PAI-1)
Placebo Comparator: Placebo
Placebo tablets. 6 tablets taken by mouth, once daily for up to 7 days
Matching placebo will be provided and participants will take 6 tablets in the evening for up to 7 days.
Other Name: TM5614 Placebo
- Clinical improvement [ Time Frame: 7 Days ]
Change of at least 2 points in the NIAID-defined ordinal scale (higher scores indicate improved outcome),:
- Hospitalized, receiving invasive mechanical ventilation or ECMO
- Hospitalized, receiving noninvasive ventilation or high-flow oxygen devices
- Hospitalized, requiring low-flow supplemental oxygen
- Hospitalized, not requiring supplemental oxygen but receiving ongoing medical care (related or not related to Covid-19)
- Hospitalized, requiring neither supplemental oxygen nor ongoing medical care (other than that specified in the protocol)
- Not hospitalized
- Sequential organ failure assessment (SOFA) score change [ Time Frame: 7 Days ]
Change in degree of organ dysfunction as defined by the Sequential Organ Failure Assessment (SOFA) Score.
The SOFA score ranges from 0 to 24 (higher scores indicate more severe organ failure), with 0 to 4 points assigned for each of 6 organ dysfunctions (ie, central nervous system, cardiovascular, respiratory, renal, coagulation, and liver).
- PAI-1 Levels [ Time Frame: 48 hours ]Change in circulating levels
- Ventilator free days [ Time Frame: 14 days ]For subjects who received mechanical ventilation, total number of days the subject was not on mechanical or non invasive mechanical ventilation while in the hospital
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04634799
|Contact: Sanjiv J Shah, MD||312 695 firstname.lastname@example.org|
|Contact: Douglas E Vaughan, MDemail@example.com|
|Principal Investigator:||Sanjiv Shah, MD||Northwestern University|