Low-Dose Tenecteplase in Covid-19 Diagnosed With Pulmonary Embolism
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|ClinicalTrials.gov Identifier: NCT04558125|
Recruitment Status : Terminated (Identification of eligible patients was slower than anticipated.)
First Posted : September 22, 2020
Results First Posted : October 26, 2021
Last Update Posted : October 26, 2021
- 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
|Condition or disease||Intervention/treatment||Phase|
|Pulmonary Embolism COVID||Drug: TNKase Drug: Placebo Drug: Enoxaparin||Phase 4|
This is a prospective, double-blind, placebo-controlled study randomizing patients with acute intermediate-risk PE who meet enrollment criteria in a 2:1 manner into intervention (TNK) versus placebo arms, respectively. There will be up to 6 sites. After 18 patients are enrolled, a safety assessment will be performed by an independent Data and Safety Monitoring Board, and if a safety issue arises, it will be considered and discussed among the investigators. The planned sample size is 45 patients (30 treatment and 15 control). Subjects will be assessed daily while hospitalized. Subjects discharged from the hospital will be asked to attend study visits at Days 14 and 30 (telephone / telemedicine, clinic or inpatient ward).
The overall objective of the study is to evaluate the clinical efficacy and safety of IV bolus tenecteplase (TNK) and therapeutic anticoagulation compared with placebo and therapeutic anticoagulation in hospitalized adults diagnosed with COVID-19 infection and acute intermediate-risk PE.
Written informed consent for participation in the study must be obtained before performing any study-related procedures (including screening evaluations). Informed Consent Forms for enrolled patients and for patients who are not subsequently enrolled will be maintained at the study site.
After informed consent is obtained, screening assessment will be completed to confirm a patient's eligibility for participation in the study. The screening visit will include medical history, physical exam and vital signs. Standard of care (SOC). labs will be reviewed. These may include INR, aPTT, PT (if patient is currently taking an anticoagulant), CBC with diff, comprehensive chemistry panel, D-dimer and Ferritin. The results of the SARS-CoV-2 will be documented. If subject is in child-bearing age and a pregnancy test was not done for SOC, a urine pregnancy test will be performed. Electrocadiogram and CTA will be reviewed.
If the patient is determined to be eligible, the study site will obtain the patient's medical record number/unique patient identification number, and treatment assignment to either interventional (TNK) or placebo will be randomly determined. Patients will be allocated to the interventional versus placebo arms in a 2:1 manner as per a computer-generated randomization schedule using permuted blocks of random sizes. The block sizes will not be disclosed to ensure concealment. A total of 30 TNK subjects versus 15 placebo controls will be enrolled.
Before the study drug/placebo is administered, the following labs will be drawn CBC with diff, comprehensive metabolic panel, CRP, Ferritin, IL-6, Fibrinogen, D-dimer, PT/PTT, LDH, lactate, troponin, creatinine kinase, and Thromboelastography (TEG). Vital signs and echocardiogram will be obtained. Shock Index will be calculated, then the infusion will begin.
Within 10 minutes (+ 5min) of infusion, a second TEG will be collected. At 6 hours after the infusion, a second Shock Index will be calculated. At 24+/- 6 hours after the bolus, a physical exam will be performed, vital signs will be collected, an echocardiogram will be performed and D-dimer, CRP, IL-6, and Ferritin will be done. TEG will be an optional addition to the 24-hour labs. Daily safety labs will include CBC and chemistry panel. SOC lab results will be collected from the chart.
Patients will have follow-up visits on Day 14 +/- 2 days and Day 30 +/- 4 days. These visits may take place via televisit or in person. Data will be collected on adverse events, vital signs and new concomitant medications. Safety labs will be obtained if visit occurs in person.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||2 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Low-Dose Tenecteplase in Covid-19 Patients With Acute Pulmonary Embolism: A Randomized, Double-Blind, Placebo-Controlled Trial|
|Actual Study Start Date :||September 8, 2020|
|Actual Primary Completion Date :||July 10, 2021|
|Actual Study Completion Date :||August 8, 2021|
Experimental: Low-dose TNKase and Standard of Care Anticoagulation
Tenecteplase (0.25 mg/kg) supplied by Genentech, Inc. as a sterile, lyophilized powder, diluted with 10mL sterile water.
All participants must also receive standard of care anticoagulation therapy.
Active Comparator: Placebo and and Standard of Care Anticoagulation
Placebo to match supplied by Genentech, Inc. as a sterile, lyophilized powder, diluted with 10mL sterile water.
All participants must also receive standard of care anticoagulation therapy.
- Percent Improvement in Shock Index (Defined as Heart Rate Divided by Systolic Blood Pressure) 6 Hours After the TNK/Placebo Bolus. [ Time Frame: 6 hours post TNK/placebo infusion ]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.
- 1. Clinical Status at 24 Hours After Administration of TNK / Placebo Based Upon 7-point Scale. [ Time Frame: 24 +/- 6 hours post TNK/placebo infusion. ]
Assessment of patient status using an ordinal scale will be recorded at baseline and once daily in the morning while hospitalized.
Level 1: Discharged (or "ready for discharge" on ambient air or < 2L suppl O2) Level 2: Non-ICU hospital ward (or "ready for hospital ward") not requiring suppl O2 Level 3: Non-ICU hospital ward (or "ready for hospital ward") requiring suppl O2 Level 4. ICU or non-ICU, requiring non-invasive ventilation or high-flow O2 Level 5. ICU, requiring intubation and mechanical ventilation Level 6: ICU, requiring ECMO or mechanical ventilation and additional organ support (e.g. vasopressors, renal replacement therapy) Level 7: Death
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04558125
|United States, California|
|Cedars-Sinai Medical Center|
|Los Angeles, California, United States, 90048|
|Principal Investigator:||Victor E Tapson, MD||Cedars-Sinai Medical Center|