Clot Dissolving Treatment for Blood Clots in the Lungs
- Conditions
- Pulmonary Embolism
- Interventions
- Drug: 0.9% Saline + Enoxaparin
- Registration Number
- NCT00680628
- Lead Sponsor
- Wake Forest University Health Sciences
- Brief Summary
The purpose of this study is to determine if tenecteplase plus enoxaparin is safe and effective in the treatment of patients with severe submassive pulmonary embolism.
- Detailed Description
This project is a phase III, six-center, randomized trial of tenecteplase to treat severe submassive (systolic blood pressure \>90 mm Hg) pulmonary embolism (PE). "Severe" requires one of the following predictors of a adverse outcome: right ventricular (RV) hypokinesis on echocardiography, hypoxemia (pulse oximetry reading \<95%, \<1000 feet above sea level), serum troponin I (abnormal at local threshold) or brain natriuretic peptide concentration \>90 pg/mL (or NT proBNP \>900 pg/mL). Patients from the emergency department or inpatients can be enrolled within 24 hours of a diagnostic positive CT angiography. After informed consent, eligible patients will be randomized to the study or placebo arm. All patients will a receive a 1mg/kg enoxaparin, SQ followed by a syringe prepared in pharmacy containing either a body weight-adjusted dose of tenecteplase or a 0.9% saline placebo, given IV push. Patients will be followed for five days post-treatment for composite acute adverse outcomes: PE-related (death, any ACLS intervention, circulatory shock, respiratory failure, need for vasopressors with organ dysfunction) and hemorrhage-related (intracranial or intraspinal hemorrhage and any other hemorrhage requiring transfusion, surgical or endoscopic intervention or a hemostatic drug). Survivors will return at three months for assessment of a delayed adverse outcomes of death or cardiopulmonary functional limitation (CFL): interval medical care for dyspnea + RV dysfunction or pulmonary hypertension on echo + either a NYHA score ≥3 or a 6 minute walk distance \<330 m. Together, the acute and delayed outcomes represent composite serious adverse outcomes (SAOs). We hypothesize an absolute 20% reduction in composite serious adverse outcomes in the study arm compared with the placebo arm. The six hospitals represent geographic diversity: Boston, Charlotte, Chicago, Denver, New Haven, and Springfield, MA. To help maintain balance between sites, the six sites will each enroll a maximum of 40 patients until the sample size of N=200 is reached, which allows the 20% effect size to be tested at α =0.05 and β=0.20 with 15% loss to follow-up. The study will employ an intent-to treat analysis. Secondary endpoints include recurrent venous thromboembolism within three months, scores from two validated quality of life questionnaire (VEINES-QOL and SF-36TM) at three months. Human subject safety include requirement that a study MD verify the presence of all inclusion and absence of exclusions in real-time, a method to allow unblinding to the clinical care team, an independent DSMB that will perform 6 interim analyses and will enforce predefined stopping criteria for either safety or efficacy.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 83
- Pulmonary vascular imaging positive for PE within the previous 24 hours
- Ability to provide written informed consent and comply with study assessments for the full duration of the study
- Age >17 years
- Evidence of severe PE: RV hypokinesis on echocardiography, abnormal troponin I or T (any non-normal including indeterminate values, using local reference thresholds) or BNP measurement >90 pg/mL or NT proBNP >900 pg/ml (not more than 6 hours prior to CT angiography and not more than 30 hours before enrollment) or a pulse oximetry reading <95% within previous two hours (<93% in Denver).
- Systolic blood pressure < 90 mm Hg at time of informed consent
- Do not resuscitate or do not intubate order
- Systemic fibrinolytic treatment within previous 7 days
- Inability to follow-up at 3 months
- Documented gastrointestinal bleeding within previous 30 days
- Active hemorrhage in any of the following sites at the time of enrollment: intraperitoneal, retroperitoneal, pulmonary, uterine, bladder, or nose.
- Head trauma causing loss of consciousness within previous 7 days
- Any history of hemorrhagic stroke
- Ischemic stroke within the past year
- Prior history of heparin-induced thrombocytopenia
- History of intraocular hemorrhage
- Intracranial metastasis
- Known inherited bleeding disorder, e.g., hemophilia
- Platelet count < 50,000/uL
- Prothrombin time with an INR >1.7
- Chest, abdominal, intracranial or spinal surgery within the previous 14 days
- Subacute bacterial endocarditis
- Pregnancy (positive pregnancy test)
- Prior enrollment in the study
- Current treatment with fondiparinux, dalteparin, a direct thrombin inhibitor or administration of a glycoprotein inhibitor within the previous 48 hours.
- Known pericarditis
- Allergy to heparins,or tenecteplase
- Elapsed time that would preclude drug or placebo administration within 24 hours after diagnosis
- Evidence of non-end stage kidney injury (creatinine clearance < 30 ml/min without chronic hemodialysis treatment; chronic hemodialysis-treated patients are eligible)
- Preexisting end-stage cardiopulmonary disease (heart failure with left ventricular ejection fraction <20%, known severe pulmonary hypertension or other lung disease causing permanent dependence upon oxygen)
- Any other condition that the investigator believes would pose a significant hazard to the subject
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 2 0.9% Saline + Enoxaparin Saline + Enoxaparin 1 Tenecteplase + Enoxaparin Tenecteplase + Enoxaparin
- Primary Outcome Measures
Name Time Method Number of Patients With Cardiogenic Shock or Respiratory Failure From Pulmonary Embolism and Number of Patietnts With Major Hemorrhage 1,2,3,4, and 5 days Number With Functional Cardiopulmonary Limitations Assessed With a Composite Measurement (Six Minute Walk Distance, Right Ventricular Function and Quality of Life Score on the SF-36) 90 days Number With Recurrent Venous Thromboembolism and/or Severe Post-phlebitic Syndrome 90 days
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (7)
University of California, Davis Medical Center
🇺🇸Sacramento, California, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Utah Hospital
🇺🇸Salt Lake City, Utah, United States
University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States