Low-Dose Tenecteplase in Covid-19 Diagnosed With Pulmonary Embolism

NCT04558125 | Terminated Phase 4 Results DMC FDA Drug

• 1 other identifier: ML42522
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

• There is a knowledge gap associated with the management of patients with COVID-19 lung injury and a laboratory picture compatible with disseminated intravascular coagulation (DIC). Clinical data to date support that COVID-19 is associated with a prothrombotic state that is not simply explained by an influx of more critically ill individuals.
• These patients suffer from severe respiratory failure; hypoxemia and ventilator dependence are the primary concerns; ARDS with respiratory failure is frequently the cause of death. Macroscopic and probable microvascular thromboembolic events are a major concern in this population.
• When DIC is associated with COVID-19, it predicts a very poor prognosis.
• This study will evaluate the clinical efficacy and safety of low-dose IV bolus tenecteplase (TNK) together with anticoagulation compared with control patients on therapeutic anticoagulation alone in hospitalized adults diagnosed with COVID-19 and acute intermediate-risk PE.
• Prospective, multicenter, randomized two-arm trial enrolling consecutive patients who meet enrollment criteria.
• The study will generate evidence that low-dose TNK together with anticoagulation is beneficial in these patients

Conditions

Pulmonary Embolism; COVID

Outcome Measures

Primary Outcomes (1)

• Percent Improvement in Shock Index (Defined as Heart Rate Divided by Systolic Blood Pressure) 6 Hours After the TNK/Placebo Bolus.

  For example, a patient may start with a heart rate of 100 beats/min and systolic blood pressure of 100 mm Hg (shock index = 1) and after therapy there may be an improvement where the heart rate is 90 beats/min, with systolic blood pressure of 110 mm Hg (shock index of 0.81), an improvement of 19%. A normal shock index is between 0.5 and 0.7 in healthy patients.

  6 hours post TNK/placebo infusion

Secondary Outcomes (1)

• 1. Clinical Status at 24 Hours After Administration of TNK / Placebo Based Upon 7-point Scale.

  24 +/- 6 hours post TNK/placebo infusion.

Study Arms (2)

Low-dose TNKase and Standard of Care Anticoagulation

EXPERIMENTAL

1. TNKase (0.25 mg/kg) bolus Other names: Tenecteplase, TNK 2. Standard of care anticoagulation (heparin or enoxaparin)

Drug: TNKase; Drug: Enoxaparin

Placebo and and Standard of Care Anticoagulation

ACTIVE COMPARATOR

1. Placebo bolus (intravenous syringe identical to that of TNK ) 2. Standard of care anticoagulation (heparin or enoxaparin)

Drug: Placebo; Drug: Enoxaparin

Interventions

TNKase DRUG

Tenecteplase (0.25 mg/kg) supplied by Genentech, Inc. as a sterile, lyophilized powder, diluted with 10mL sterile water.

Also known as: Tenecteplase, TNK

Low-dose TNKase and Standard of Care Anticoagulation

Placebo DRUG

Placebo to match supplied by Genentech, Inc. as a sterile, lyophilized powder, diluted with 10mL sterile water.

Placebo and and Standard of Care Anticoagulation

Enoxaparin DRUG

All participants must also receive standard of care anticoagulation therapy.

Also known as: Low molecular weight heparin, Lovenox, Enoxaparin sodium, Heparin, Heparin sodium

Low-dose TNKase and Standard of Care Anticoagulation; Placebo and and Standard of Care Anticoagulation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or non-pregnant female adult ≥18 years of age, but \< 75 years of age at time of enrollment.
• Laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen \< 28 days prior to randomization, OR person under investigation (PUI) of COVID-19 with pulmonary infiltrates and elevated ferritin and CRP level.
• Acute intermediate-risk pulmonary embolism defined as:
• Presence of acute pulmonary embolism confirmed by diagnostic imaging (computed tomographic angiography, ventilation-perfusion scan, or invasive pulmonary angiography) AND
• Presence of clot burden with at least one lobar artery involved OR bilateral with at least segmental branches OR unilateral clot in at least multiple segmental branches.
• Subject (or legally authorized representative) provides written informed consent prior to the performance of any study procedures.
• In the Investigator's judgement, patient has the ability to comply with the study protocol, and understands and agrees to comply with planned TNK bolus versus placebo.

You may not qualify if:

• Anticipated transfer to another hospital (which is not a study site) within 72 hours
• Allergy or contraindications to TNK
• Contraindications to systemic anticoagulation
• Active bleeding
• Major GI or GU bleed within the past 3 weeks
• History of hemorrhagic stroke
• History of acute ischemic stroke in the last 90 days
• High-risk (massive) acute PE (PE associated with hypotension (systolic BP \< 90 mmHg for \> 15 min).
• PE associated with syncope and any degree of head trauma
• PE meeting criteria for intermediate-risk PE and thus for enrollment, but with clinical evidence of deterioration such that the Investigator deems the patient not appropriate for enrollment.
• Administration of thrombolytic agent within the previous 7 days
• Pulmonary thrombectomy within the previous 30 days
• Uncontrolled hypertension defined as systolic blood pressure \>180 mm Hg and/or diastolic blood pressure \>110 mm Hg at randomization
• Severe ARDS (P/F ratio \< 100)
• Platelet count lower than 80,000/mm3

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

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Related Links

• Stroke Early Management Guidelines
• TEG max clot strength is consistently elevated and may be predictive of COVID-19 status at the time of ICU admission
• A randomized trial of anticoagulation strategies in COVID-19
• Preventing COVID-19 complications with low- and high-dose anticoagulation (COVID-HEP)
• Trial evaluating efficacy and safety of anticoagulation in patients with COVID-19 infection, nested in the Corimmuno-19 Cohort (CORIMMUNO-COAG)
• Risk assessment of venous thromboembolism and bleeding in COVID-19 patients
• Clinical pathology of critical patient with novel coronavirus pneumonia (COVID-19)
• Generalized odds ratios for ordinal data

MeSH Terms

Conditions

Pulmonary Embolism

Interventions

Tenecteplase; Enoxaparin; Heparin, Low-Molecular-Weight; enoxaparin sodium; Heparin

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Embolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tissue Plasminogen Activator; Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Glycosaminoglycans; Polysaccharides; Carbohydrates

Limitations and Caveats

The study was terminated early due to enrollment being slower than anticipated, with study enrollment highly dependent upon COVID-19 surge patterns. We were otherwise hopeful to enroll and complete all assessments for this study.

Results Point of Contact

• Title: Victor Tapson, MD
• Organization: Cedars-Sinai Medical Center

Victor.Tapson@cshs.org

919-971-6441

Study Officials

• Victor E Tapson, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: September 19, 2020
• First Posted: September 22, 2020
• Study Start: September 8, 2020
• Primary Completion: July 10, 2021
• Study Completion: August 8, 2021
• Last Updated: October 26, 2021
• Results First Posted: October 26, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)