Tenecteplase in Patients With COVID-19

Phase 2

Completed

Conditions: COVID-19
Respiratory Failure
ARDS

Interventions: Drug: Placebo
Drug: Tenecteplase

Registration Number: NCT04505592

Lead Sponsor: Hooman Poor

Brief Summary: This is a placebo-controlled, double blind, randomized, Phase II dose escalation study intended to evaluate the potential safety and efficacy of tenecteplase for the treatment of COVID-19 associated respiratory failure. The hypothesis is that administration of the drug, in conjunction with heparin anticoagulation, will improve patients' clinical outcomes.

Detailed Description: Patients with COVID-19 who suffer from acute hypoxemic respiratory failure have a poor prognosis. COVID-19 has been associated with a hyperinflammatory and hypercoagulable state, leading to a range of thromboembolic complications from pulmonary embolism to ischemic stroke. Furthermore, emerging data suggest that the associated acute respiratory failure is, at least in part, due to pulmonary vascular disease caused by micro- and/or macro-emboli, creating pulmonary vascular shunting and dead-space ventilation. In this placebo-controlled, double blind, randomized, Phase II dose escalation study, we plan to evaluate the clinical efficacy and safety of low-dose IV bolus tenecteplase together with anticoagulation compared with control patients on therapeutic anticoagulation alone in hospitalized adults diagnosed with COVID-19 respiratory failure with elevated D-dimer. We believe these patients can be successfully treated without significantly increasing the risk of major bleeding while improving recovery rates, shorten hospitalization time, and perhaps ultimately prove to improve survival.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 13

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo control
Tenecteplase	Tenecteplase	First 20 patients randomized to treatment will receive tenecteplase 0.25 mg/kg (maximum 25 mg). Last 20 patients randomized to treatment will receive tenecteplase 0.50 mg/kg (maximum 40 mg).

Primary Outcome Measures

Name	Time	Method
Number of Participants Free of Respiratory Failure	28 Days	The number of patients free of respiratory failure defined as not requiring high flow nasal cannula, non-rebreather, noninvasive positive pressure ventilation, or mechanical ventilation at 28 days
Number of Participants With Occurrences of Bleeding	28 days	Safety as assessed by number of participants with occurrences of intracranial bleeding or major bleeding

Secondary Outcome Measures

Name	Time	Method
Number of Vasopressor-free Days	28 days	Number of vasopressor-free days over 28 days period
Number of Participants With Need for Renal Replacement Therapy	28 days	Number of patients who underwent renal replacement treatment for their renal failure
Number of Participants With In-hospital Deaths at 14 Days	14 days	Number of patients who expired in the hospital within the first 14 days of their participation in the study
Number of Participants With Death at 28 Days	28 days	Number of participants who expired by 28 days/end of study
Number of Vasopressor Doses at 24 Hours	24 hours and 72 hours
P/F Ratio	24 hours and 72 hours	The P/F ratio equals the arterial pO2 ("P") from the ABG divided by the FIO2 ("F") - the fraction (percent) of inspired oxygen that the patient is receiving expressed as a decimal (40% oxygen = FIO2 of 0.40). Ratio of arterial pO2 over fraction of inspired oxygen that the person is receiving. Normal P/F Ratio is ≥ 400. 300 to 200 is considered mild ARDS 200 to 100 is considered moderate ARDS Anything below 100 is considered severe ARDS.
Number of ICU-free Days	28 days	Number of days the patient spent outside the ICU
Hospital Length of Stay	up to 29 days	Length of time the patient spent in the hospital, including ICU
Number of Ventilator-free Days	28 days	Number of ventilator-free days in 28 days period
Number of Respiratory Failure-free Days	28 days	Respiratory failure-free defined as not requiring high flow nasal cannula, non-rebreather, noninvasive positive pressure ventilation, or mechanical ventilation. Number of respiratory failure-free days in 28 days period.
Number of Participants With New-onset Renal Failure	28 days	Number of patients who experienced renal failure during the course of the study