Low Molecular Weight Heparin for 72 Hours Followed by Dabigatran for Acute Intermediate-Risk Pulmonary Embolism. (PEITHO-2)
Primary Purpose
Pulmonary Embolism
Status
Terminated
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
Dabigatran
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Embolism
Eligibility Criteria
Inclusion Criteria:
- Age ≥18 years
- Objectively confirmed diagnosis of acute PE by multidetector CT angiography, ventilation/perfusion lung scan, or selective invasive pulmonary angiography, according to established diagnostic criteria, with or without symptomatic deep vein thrombosis
- Absence of hemodynamic collapse, or decompensation, at presentation; Hemodynamic collapse or decompensation
Intermediate-risk category of PE severity indicated by a positive (score ≥1) simplified pulmonary embolism severity index (sPESI), in combination with the presence of at least one of the following criteria at presentation:
- At least one sign of RV pressure overload/dysfunction on CT angiography or echocardiography
- Signs of myocardial injury as indicated by elevated troponin levels
- Signs of (RV) failure as indicated by NT-proBNP levels >600 pg/ml at baseline.
- Ability of the subject to understand the character and individual consequences of the clinical trial; signed and dated informed consent of the subject available before the start of any specific trial procedures
Exclusion Criteria:
- Pregnancy (a negative serum or urine pregnancy test should be available for women of child-bearing potential before study inclusion) or lactation
- Women of childbearing potential who do not practice a medically accepted highly effective contraception during the trial and one month beyond
- History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product
- Participation in another clinical trial during the present clinical trial or within the last three months
- Medical or psychological condition that would not permit completion of the trial or signing of informed consent
- Use of a fibrinolytic agent, surgical thrombectomy, interventional (catheter-directed) thrombus aspiration or lysis, or use of a cava filter to treat the index episode of PE
- Treatment with any therapeutically dosed anticoagulant for more than 48 hours prior to enrolment
- Need for long-term treatment with a low molecular weight heparin, vitamin K antagonists or NOAC, for an indication other than the index PE episode, or for antiplatelet agents except acetylsalicylic acid at a dosage ≤100 mg/day;
- Active bleeding or known significant bleeding risk (e.g., gastrointestinal ulcer, malignant neoplasms, injuries or recent surgeries of the brain, spinal cord or eyes, recent intracranial bleedings, known or suspected esophagus varices, aneurysms or intraspinal or intracranial vascular abnormalities)
- Artificial heart valves requiring treatment with an anticoagulant
- Renal insufficiency with estimated creatinine clearance <30 ml/min/1.73m2
- Chronic liver disease with aminotransferase levels two times or more above the local upper limit of normal range
- Concomitant administration of strong inhibitors of P-glycoprotein like ketoconazole, cyclosporin, itraconazole or dronedarone
- Unwillingness or inability to adhere to treatment or to the follow-up visits
- Life expectancy less than 6 months
Sites / Locations
- Center for Thrombosis and Hemostasis, University Medical Center Mainz
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dabigatran treatment
Arm Description
Low molecular weight heparin for 72 hours followed by 6 months of dabigatran
Outcomes
Primary Outcome Measures
Occurrence of symptomatic venous thromboembolism (VTE) or pulmonary embolism (PE) related death (yes/no)
Secondary Outcome Measures
Recovery of right ventricle (RV) function
Temporal pattern of changes in NT-proBNP (N-terminal prohormone of brain natriuretic peptide) levels
Death from any cause
Pulmonary embolism (PE) related death, or PE-related or hemodynamic collapse or decompensation
Overall duration of hospital stay
Major bleeding
Clinically relevant bleeding
Serious adverse events (SAE)
Full Information
NCT ID
NCT02596555
First Posted
November 3, 2015
Last Updated
February 12, 2020
Sponsor
Prof. Stavros Konstantinides, MD
Collaborators
European Georges Pompidou Hospital
1. Study Identification
Unique Protocol Identification Number
NCT02596555
Brief Title
Low Molecular Weight Heparin for 72 Hours Followed by Dabigatran for Acute Intermediate-Risk Pulmonary Embolism.
Acronym
PEITHO-2
Official Title
Safety and Efficacy of Low Molecular Weight Heparin for 72 Hours Followed by Dabigatran for the Treatment of Acute Intermediate-Risk Pulmonary Embolism
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Terminated
Why Stopped
Interim results suggested a reduction of sample size.
Anticipated length of enrolment period with resulting funding issues to pose a threat to the study.
Study Start Date
January 2016 (Actual)
Primary Completion Date
February 2020 (Actual)
Study Completion Date
February 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Prof. Stavros Konstantinides, MD
Collaborators
European Georges Pompidou Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This prospective, multicenter, multinational, phase IV, interventional single-armed (management) trial will focus on the safety, efficacy and cost-effectiveness of a new oral anticoagulant in the treatment of patients with acute intermediate-risk PE based on validated imaging (echocardiographic or CT angiographic) and laboratory biomarker (circulating levels of cardiac troponins and natriuretic peptides) parameters and their combinations.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Embolism
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
400 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dabigatran treatment
Arm Type
Experimental
Arm Description
Low molecular weight heparin for 72 hours followed by 6 months of dabigatran
Intervention Type
Drug
Intervention Name(s)
Dabigatran
Other Intervention Name(s)
Pradaxa
Intervention Description
Low molecular weight heparin for 72 hours followed by 6 months of dabigatran
Primary Outcome Measure Information:
Title
Occurrence of symptomatic venous thromboembolism (VTE) or pulmonary embolism (PE) related death (yes/no)
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Recovery of right ventricle (RV) function
Time Frame
6±1 days or upon discharge (whichever comes first), 6 months
Title
Temporal pattern of changes in NT-proBNP (N-terminal prohormone of brain natriuretic peptide) levels
Time Frame
6±1 days or upon discharge (whichever comes first), 6 months
Title
Death from any cause
Time Frame
30 days
Title
Pulmonary embolism (PE) related death, or PE-related or hemodynamic collapse or decompensation
Time Frame
30 days
Title
Overall duration of hospital stay
Time Frame
6 months
Title
Major bleeding
Time Frame
6 months
Title
Clinically relevant bleeding
Time Frame
6 months
Title
Serious adverse events (SAE)
Time Frame
72 hours, 30 days, 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥18 years
Objectively confirmed diagnosis of acute PE by multidetector CT angiography, ventilation/perfusion lung scan, or selective invasive pulmonary angiography, according to established diagnostic criteria, with or without symptomatic deep vein thrombosis
Absence of hemodynamic collapse, or decompensation, at presentation; Hemodynamic collapse or decompensation
Intermediate-risk category of PE severity indicated by a positive (score ≥1) simplified pulmonary embolism severity index (sPESI), in combination with the presence of at least one of the following criteria at presentation:
At least one sign of RV pressure overload/dysfunction on CT angiography or echocardiography
Signs of myocardial injury as indicated by elevated troponin levels
Signs of (RV) failure as indicated by NT-proBNP levels >600 pg/ml at baseline.
Ability of the subject to understand the character and individual consequences of the clinical trial; signed and dated informed consent of the subject available before the start of any specific trial procedures
Exclusion Criteria:
Pregnancy (a negative serum or urine pregnancy test should be available for women of child-bearing potential before study inclusion) or lactation
Women of childbearing potential who do not practice a medically accepted highly effective contraception during the trial and one month beyond
History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product
Participation in another clinical trial during the present clinical trial or within the last three months
Medical or psychological condition that would not permit completion of the trial or signing of informed consent
Use of a fibrinolytic agent, surgical thrombectomy, interventional (catheter-directed) thrombus aspiration or lysis, or use of a cava filter to treat the index episode of PE
Treatment with any therapeutically dosed anticoagulant for more than 48 hours prior to enrolment
Need for long-term treatment with a low molecular weight heparin, vitamin K antagonists or NOAC, for an indication other than the index PE episode, or for antiplatelet agents except acetylsalicylic acid at a dosage ≤100 mg/day;
Active bleeding or known significant bleeding risk (e.g., gastrointestinal ulcer, malignant neoplasms, injuries or recent surgeries of the brain, spinal cord or eyes, recent intracranial bleedings, known or suspected esophagus varices, aneurysms or intraspinal or intracranial vascular abnormalities)
Artificial heart valves requiring treatment with an anticoagulant
Renal insufficiency with estimated creatinine clearance <30 ml/min/1.73m2
Chronic liver disease with aminotransferase levels two times or more above the local upper limit of normal range
Concomitant administration of strong inhibitors of P-glycoprotein like ketoconazole, cyclosporin, itraconazole or dronedarone
Unwillingness or inability to adhere to treatment or to the follow-up visits
Life expectancy less than 6 months
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stavros Konstantinides, Prof., MD
Organizational Affiliation
Center for Thrombosis and Hemostasis, University Medical Center Mainz
Official's Role
Principal Investigator
Facility Information:
Facility Name
Center for Thrombosis and Hemostasis, University Medical Center Mainz
City
Mainz
ZIP/Postal Code
55131
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
34363769
Citation
Klok FA, Toenges G, Mavromanoli AC, Barco S, Ageno W, Bouvaist H, Brodmann M, Cuccia C, Couturaud F, Dellas C, Dimopoulos K, Duerschmied D, Empen K, Faggiano P, Ferrari E, Galie N, Galvani M, Ghuysen A, Giannakoulas G, Huisman MV, Jimenez D, Kozak M, Lang IM, Lankeit M, Meneveau N, Munzel T, Palazzini M, Petris AO, Piovaccari G, Salvi A, Schellong S, Schmidt KH, Verschuren F, Schmidtmann I, Meyer G, Konstantinides SV; PEITHO-2 investigators. Early switch to oral anticoagulation in patients with acute intermediate-risk pulmonary embolism (PEITHO-2): a multinational, multicentre, single-arm, phase 4 trial. Lancet Haematol. 2021 Sep;8(9):e627-e636. doi: 10.1016/S2352-3026(21)00203-9. Epub 2021 Aug 4.
Results Reference
derived
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Low Molecular Weight Heparin for 72 Hours Followed by Dabigatran for Acute Intermediate-Risk Pulmonary Embolism.
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