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Clot Dissolving Treatment for Blood Clots in the Lungs

Primary Purpose

Pulmonary Embolism

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Tenecteplase + Enoxaparin
0.9% Saline + Enoxaparin
Sponsored by
Wake Forest University Health Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Embolism focused on measuring Pulmonary Embolism, Tenecteplase, Enoxaparin, Thrombosis, Fibrinolytics

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California, Davis Medical Center
  • University of Colorado Hospital
  • Northwestern Memorial Hospital
  • Massachusetts General Hospital
  • Carolinas Medical Center
  • Rhode Island Hospital
  • University of Utah Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

2

1

Arm Description

Saline + Enoxaparin

Tenecteplase + Enoxaparin

Outcomes

Primary Outcome Measures

Number of Patients With Cardiogenic Shock or Respiratory Failure From Pulmonary Embolism and Number of Patietnts With Major Hemorrhage
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)
Number With Recurrent Venous Thromboembolism and/or Severe Post-phlebitic Syndrome

Secondary Outcome Measures

Full Information

First Posted
May 16, 2008
Last Updated
October 7, 2022
Sponsor
Wake Forest University Health Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT00680628
Brief Title
Clot Dissolving Treatment for Blood Clots in the Lungs
Official Title
Randomized Trial of Tenecteplase to Treat Severe Submassive Pulmonary Embolism
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Terminated
Why Stopped
PI changed institution and impossible to solve problem with contract's sites
Study Start Date
May 2008 (undefined)
Primary Completion Date
May 2012 (Actual)
Study Completion Date
October 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wake Forest University Health Sciences

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Embolism
Keywords
Pulmonary Embolism, Tenecteplase, Enoxaparin, Thrombosis, Fibrinolytics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
83 (Actual)

8. Arms, Groups, and Interventions

Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Saline + Enoxaparin
Arm Title
1
Arm Type
Experimental
Arm Description
Tenecteplase + Enoxaparin
Intervention Type
Drug
Intervention Name(s)
Tenecteplase + Enoxaparin
Intervention Description
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 Type
Drug
Intervention Name(s)
0.9% Saline + Enoxaparin
Intervention Description
Enoxaparin: 1 mg/kg within 12 hours before receiving saline.
Primary Outcome Measure Information:
Title
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
Title
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
Title
Number With Recurrent Venous Thromboembolism and/or Severe Post-phlebitic Syndrome
Time Frame
90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey A Kline, MD
Organizational Affiliation
Carolinas Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
University of Colorado Hospital
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Northwestern Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Carolinas Medical Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
University of Utah Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
33857326
Citation
Zuo Z, Yue J, Dong BR, Wu T, Liu GJ, Hao Q. Thrombolytic therapy for pulmonary embolism. Cochrane Database Syst Rev. 2021 Apr 15;4(4):CD004437. doi: 10.1002/14651858.CD004437.pub6.
Results Reference
derived
PubMed Identifier
25433511
Citation
Stewart LK, Peitz GW, Nordenholz KE, Courtney DM, Kabrhel C, Jones AE, Rondina MT, Diercks DB, Klinger JR, Kline JA. Contribution of fibrinolysis to the physical component summary of the SF-36 after acute submassive pulmonary embolism. J Thromb Thrombolysis. 2015 Aug;40(2):161-6. doi: 10.1007/s11239-014-1155-5.
Results Reference
derived

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Clot Dissolving Treatment for Blood Clots in the Lungs

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