Clinical trial NCT00680628
Conditions: Pulmonary Embolism
Keywords: Pulmonary Embolism Tenecteplase Enoxaparin Thrombosis Fibrinolytics
Sponsor: Wake Forest University Health Sciences
Start date: 2008-05-01; Completion date: 2012-10-01
Enrollment: 83 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: Saline + Enoxaparin arm 2: Tenecteplase + Enoxaparin
Interventions: intervention 1: Tenecteplase + Enoxaparin intervention 2: 0.9% Saline + Enoxaparin
Intervention descriptions: intervention 1: Enoxaparin: 1 mg/kg within 12 hours before receiving tenecteplase.Subsequently, patients will receive 1 mg/kg enoxaparin SQ Q12 hours until discontinuation is clinically indicated.

Tenecteplase:will be administered using a tiered-dosing schedule according to patient weight: \<60Kg=30mg; ≥60Kg to \<70Kg=35mg; ≥70Kg to \<80Kg=40mg; ≥80Kg to \<90Kg=45mg; ≥90Kg=50mg intervention 2: Enoxaparin: 1 mg/kg within 12 hours before receiving saline.

Protocol documents: