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Covid19Phase 1/2NCT04634799

Study To antagOnize Plasminogen Activator Inhibitor-1 in Severe COVID-19

A Phase 1/2 study testing TM5614 in people with Covid19, run by Northwestern University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a single-center, randomized double blind placebo controlled trial to evaluate the efficacy and safety of novel PAI-1 inhibitor (TM5614) for high-risk patients hospitalized with severe COVID-19 at Northwestern Memorial Hospital. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Covid19
What is being tested?
TM5614
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
9 participants
Where
1 siteUnited States
Study dates
8 Jan 2021to 30 Aug 2021
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adults ≥65 years old or < 65 years old AND at least one major cardiometabolic comorbidity (diabetes, hypertension, or cardiovascular disease)
  • Established diagnosis of COVID-19 as evidenced by a positive nasopharyngeal or bronchoalveolar lavage viral PCR for SARS-CoV2
  • Requiring supplemental oxygen

Who cannot join

  • Age <18 years old
  • Pregnancy or breast-feeding
  • Known contraindication to tissue plasminogen activator (tPA), including
  • Active internal bleeding
  • History of cerebrovascular accident
  • Recent intracranial or intraspinal surgery or trauma
Show all 23Show fewer
  • Intracranial neoplasm, arteriovenous malformation or aneurysm
  • Known bleeding diathesis
  • Severe uncontrolled hypertension (SBP>200 persistently >12 hours)
  • Currently receiving therapeutic dose anticoagulation (specifically will exclude those with potential drug-drug interaction such as heparin, apixaban, warfarin)
  • Platelets <50,000
  • Hematocrit <30%
  • Not hemodynamically stable in the preceding 4 hours (symptomatic hypotension or systolic BP <95 mmHg at 2 out of 3 measurements)
  • Concomitant illness, physical impairment or mental condition which in the opinion of the study team / primary care physician could interfere with the conduct of the study including outcome assessment
  • Other patient characteristics (not thought to be related to COVID-19) that portend a very poor prognosis (e.g., severe liver failure, metastatic malignancy)
  • Participation in a concurrent interventional medical investigation or pharmacologic clinical trial. Patients in observational, natural history or epidemiological studies not involving an intervention are eligible.
  • Participant's responsible attending physician believes it is not appropriate for participant to participate in the study.
  • Inability or unwillingness to provide written informed consent
  • Involvement in the planning and/or conduct of the study
  • Previous randomization in the present study
  • Unable to complete study procedures.
  • Patients with active venothromboembolic disease
  • Patients who are receiving other investigational agents for COVID-19.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Northwestern University

    Chicago, Illinois, 60611

Other trials in United States

About this study

Official title: Study To antagOnize Plasminogen Activator Inhibitor-1 in Severe COVID-19 (STOP Severe COVID-19)

This is a single-center, randomized double blind placebo controlled trial to evaluate the efficacy and safety of novel PAI-1 inhibitor (TM5614) for high-risk patients hospitalized with severe COVID-19 at Northwestern Memorial Hospital. The patients will be randomized in a 1:1 ratio to receive standard of care plus TM5614 or standard of care plus placebo.

Read the detailed description

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.

Conditions
Covid19
Being tested
TM5614, Placebo
Keywords
PAI-1, TM5614, Plasminogen Activator Inhibitor
Medical subject headings
COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TM5614Drug

    Also called Plasminogen activator inhibitor-1 (PAI-1)

    TM5614 is provided in 30 mg tablets and 6 tablets (180 mg) will be taken in the evening for up to 7 days.

  • PlaceboOther

    Also called TM5614 Placebo

    Matching placebo will be provided and participants will take 6 tablets in the evening for up to 7 days.

Study groups in NCT04634799
Study groupRoleWhat they receive
TM5614Active comparatorTM5614 30 mg tablets. 6 tablets (180 mg) taken by mouth, once daily for up to 7 days
Receives: Drug: TM5614
PlaceboPlacebo comparatorPlacebo tablets. 6 tablets taken by mouth, once daily for up to 7 days
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Clinical Improvement

    Change of at least 2 points in the NIAID-defined ordinal scale (higher scores indicate improved outcome),:

    1. Death
    2. Hospitalized, receiving invasive mechanical ventilation or ECMO
    3. Hospitalized, receiving noninvasive ventilation or high-flow oxygen devices
    4. Hospitalized, requiring low-flow supplemental oxygen
    5. Hospitalized, not requiring supplemental oxygen but receiving ongoing medical care (related or not related to Covid-19)
    6. Hospitalized, requiring neither supplemental oxygen nor ongoing medical care (other than that specified in the protocol)
    7. Not hospitalized

    Measured: 7 Days

Secondary outcomes (2)

  1. Sequential Organ Failure Assessment (SOFA) Score Change

    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).

    Measured: 7 Days

  2. PAI-1 Levels

    Change in circulating PAI-1 Levels (ng/mL) at discharge from baseline

    Measured: 48 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Nov 2020
  2. Study start8 Jan 2021
  3. Primary completion15 May 2021
  4. Study completion30 Aug 2021

Why it stopped: Enrollment challenges due to decline in COVID

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04634799
Sponsor's protocol ID
STU00213262
Status last verified
Aug 2026
First submitted
17 Nov 2020
Last updated
25 Sep 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Chang D, Lin M, Wei L, Xie L, Zhu G, Dela Cruz CS, Sharma L. Epidemiologic and Clinical Characteristics of Novel Coronavirus Infections Involving 13 Patients Outside Wuhan, China. JAMA. 2020 Mar 17;323(11):1092-1093. doi: 10.1001/jama.2020.1623.

    PubMed 32031568

  • Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30.

    PubMed 32007143

  • Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28.

    PubMed 32109013

  • Liu YC, Liao CH, Chang CF, Chou CC, Lin YR. A Locally Transmitted Case of SARS-CoV-2 Infection in Taiwan. N Engl J Med. 2020 Mar 12;382(11):1070-1072. doi: 10.1056/NEJMc2001573. Epub 2020 Feb 12. No abstract available.

    PubMed 32050059

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing TM5614 in people with Covid19, run by Northwestern University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Sep 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical Improvement (time frame: 7 Days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04634799, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2026.

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