Clot Dissolving Treatment for Blood Clots in the Lungs

This study has been terminated.
(PI changed institution and impossible to solve problem with contract's sites)
Sponsor:
Information provided by (Responsible Party):
Jeffrey Kline, Carolinas Healthcare System
ClinicalTrials.gov Identifier:
NCT00680628
First received: May 16, 2008
Last updated: July 22, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Pulmonary Embolism
Drug: Tenecteplase + Enoxaparin
Drug: 0.9% Saline + Enoxaparin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Trial of Tenecteplase to Treat Severe Submassive Pulmonary Embolism

Resource links provided by NLM:


Further study details as provided by Carolinas Healthcare System:

Primary Outcome Measures:
  • Number of Patients With Cardiogenic Shock or Respiratory Failure From Pulmonary Embolism and Number of Patietnts With Major Hemorrhage [ Time Frame: 1,2,3,4, and 5 days ] [ Designated as safety issue: Yes ]
  • 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) [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
  • Number With Recurrent Venous Thromboembolism and/or Severe Post-phlebitic Syndrome [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]

Enrollment: 83
Study Start Date: May 2008
Study Completion Date: October 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 2
Saline + Enoxaparin
Drug: 0.9% Saline + Enoxaparin
Enoxaparin: 1 mg/kg within 12 hours before receiving saline.
Experimental: 1
Tenecteplase + Enoxaparin
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


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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00680628

Locations
United States, California
University of California, Davis Medical Center
Sacramento, California, United States, 95817
United States, Colorado
University of Colorado Hospital
Aurora, Colorado, United States, 80045
United States, Illinois
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, North Carolina
Carolinas Medical Center
Charlotte, North Carolina, United States, 28203
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
United States, Utah
University of Utah Hospital
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
Jeffrey Kline
Investigators
Principal Investigator: Jeffrey A Kline, MD Carolinas Medical Center
  More Information

No publications provided

Responsible Party: Jeffrey Kline, Director, Emergency Medicine Research, Carolinas Healthcare System
ClinicalTrials.gov Identifier: NCT00680628     History of Changes
Other Study ID Numbers: 01-08-01A
Study First Received: May 16, 2008
Results First Received: October 29, 2013
Last Updated: July 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Carolinas Healthcare System:
Pulmonary Embolism
Tenecteplase
Enoxaparin
Thrombosis
Fibrinolytics

Additional relevant MeSH terms:
Pulmonary Embolism
Embolism
Lung Diseases
Respiratory Tract Diseases
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Tenecteplase
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on October 01, 2014