Pulmonary EmbolismPhase 3NCT00680628
Clot Dissolving Treatment for Blood Clots in the Lungs
A Phase 3 study testing Tenecteplase + Enoxaparin and 0.9% Saline + Enoxaparin in people with Pulmonary Embolism, run by Wake Forest University Health Sciences at 7 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Embolism
- What is being tested?
- Tenecteplase + Enoxaparin and 0.9% Saline + Enoxaparin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 83 participants
- Where
- 7 sitesUnited States
- Study dates
- May 2008to Oct 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
Show all 26Show fewer
- 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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
University of Colorado Hospital
Aurora, Colorado, 80045
Massachusetts General Hospital
Boston, Massachusetts, 02114
Carolinas Medical Center
Charlotte, North Carolina, 28203
Northwestern Memorial Hospital
Chicago, Illinois, 60611
Rhode Island Hospital
Providence, Rhode Island, 02903
University of California, Davis Medical Center
Sacramento, California, 95817
University of Utah Hospital
Salt Lake City, Utah, 84132
About this study
Official title: Randomized Trial of Tenecteplase to Treat Severe Submassive Pulmonary Embolism
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.
Read the 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.
- Conditions
- Pulmonary Embolism
- Being tested
- Tenecteplase + Enoxaparin, 0.9% Saline + Enoxaparin
- Keywords
- Pulmonary Embolism, Tenecteplase, Enoxaparin, Thrombosis, Fibrinolytics
- Medical subject headings
- Pulmonary Embolism, Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tenecteplase + EnoxaparinDrug
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 + EnoxaparinDrug
Enoxaparin: 1 mg/kg within 12 hours before receiving saline.
| Study group | Role | What they receive |
|---|---|---|
| 2 | Placebo comparator | Saline + Enoxaparin Receives: Drug: 0.9% Saline + Enoxaparin |
| 1 | Experimental | Tenecteplase + Enoxaparin Receives: Drug: Tenecteplase + Enoxaparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Cardiogenic Shock or Respiratory Failure From Pulmonary Embolism and Number of Patietnts With Major Hemorrhage
Measured: 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)
Measured: 90 days
Number With Recurrent Venous Thromboembolism and/or Severe Post-phlebitic Syndrome
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2008 (estimated)
- Study startMay 2008
- Primary completionMay 2012
- Study completionOct 2012
Why it stopped: PI changed institution and impossible to solve problem with contract's sites
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pulmonary EmbolismStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 83 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jeffrey A Kline, MD, Principal investigator, Carolinas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00680628
- Sponsor's protocol ID
- 01-08-01A
- Status last verified
- Oct 2022
- First submitted
- 16 May 2008
- Last updated
- 12 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 33857326Stewart 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.
PubMed 25433511
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of Tenecteplase to Treat Severe Submassive Pulmonary Embolism
- ClinicalTrials.gov ID
- NCT00680628
- Acronym / sponsor ID
- 01-08-01A
- Conditions
- Pulmonary Embolism
- Keywords
- Pulmonary Embolism, Tenecteplase, Enoxaparin, Thrombosis, Fibrinolytics
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI changed institution and impossible to solve problem with contract's sites
- Enrolment
- 83 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Study start
- May 2008
- Primary completion
- May 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 20 May 2008 (estimated)
- Results
- Posted 11 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 2 | Placebo comparator | Drug: 0.9% Saline + EnoxaparinSaline + Enoxaparin |
| 1 | Experimental | Drug: Tenecteplase + EnoxaparinTenecteplase + Enoxaparin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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).
Key exclusion criteria (26 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tenecteplase + EnoxaparinEnoxaparin: 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 | Drug | 1 |
| 0.9% Saline + EnoxaparinEnoxaparin: 1 mg/kg within 12 hours before receiving saline. | Drug | 2 |
Primary outcome
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
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
Number With Recurrent Venous Thromboembolism and/or Severe Post-phlebitic Syndrome
Time frame: 90 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33857326Zuo 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.
- Derived from this study: PubMed 25433511Stewart 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey A Kline, MD principal investigator
Carolinas Medical Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tenecteplase + Enoxaparin and 0.9% Saline + Enoxaparin in people with Pulmonary Embolism, run by Wake Forest University Health Sciences at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00680628, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2022.