Clot Dissolving Treatment for Blood Clots in the Lungs

Pulmonary Embolism Clinical Trial

Official title:

Randomized Trial of Tenecteplase to Treat Severe Submassive Pulmonary Embolism

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00680628
• Other study ID #: 01-08-01A
• Status: Terminated
• Phase: Phase 3
• Start date: May 2008
• Est. completion date: October 2012

Study information

• Verified date: October 2022
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 83
• Est. completion date: October 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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).

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Embolism
• Pulmonary Embolism

Intervention

Drug:
• Tenecteplase + Enoxaparin
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
• 0.9% Saline + Enoxaparin
Enoxaparin: 1 mg/kg within 12 hours before receiving saline.

Locations

Country	Name	City	State
United States	University of Colorado Hospital	Aurora	Colorado
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Rhode Island Hospital	Providence	Rhode Island
United States	University of California, Davis Medical Center	Sacramento	California
United States	University of Utah Hospital	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Number With Recurrent Venous Thromboembolism and/or Severe Post-phlebitic Syndrome		90 days