Low Molecular Weight Heparin for 72 Hours Followed by Dabigatran for Acute Intermediate-Risk Pulmonary Embolism.

NCT02596555 | Terminated Phase 4 DMC

• 1 other identifier: PEITHO-2
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

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.

Conditions

Pulmonary Embolism

Outcome Measures

Primary Outcomes (1)

• Occurrence of symptomatic venous thromboembolism (VTE) or pulmonary embolism (PE) related death (yes/no)

  6 months

Secondary Outcomes (8)

• Recovery of right ventricle (RV) function

  6±1 days or upon discharge (whichever comes first), 6 months

• Temporal pattern of changes in NT-proBNP (N-terminal prohormone of brain natriuretic peptide) levels

  6±1 days or upon discharge (whichever comes first), 6 months

• Death from any cause

  30 days

• Pulmonary embolism (PE) related death, or PE-related or hemodynamic collapse or decompensation

  30 days

• Overall duration of hospital stay

  6 months

Study Arms (1)

Dabigatran treatment

EXPERIMENTAL

Low molecular weight heparin for 72 hours followed by 6 months of dabigatran

Drug: Dabigatran

Interventions

Dabigatran DRUG

Low molecular weight heparin for 72 hours followed by 6 months of dabigatran

Also known as: Pradaxa

Dabigatran treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Prof. Stavros Konstantinides, MD: lead
• European Georges Pompidou Hospital: collaborator

Study Sites (1)

Center for Thrombosis and Hemostasis, University Medical Center Mainz

Mainz, 55131, Germany

Location

Related Publications (1)

• 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.

  PMID: 34363769 DERIVED

MeSH Terms

Conditions

Pulmonary Embolism

Interventions

Dabigatran

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Embolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Stavros Konstantinides, Prof., MD

  Center for Thrombosis and Hemostasis, University Medical Center Mainz

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Director of Center for Thrombosis and Hemostasis, University Medical Center Mainz

Study Record Dates

• First Submitted: November 3, 2015
• First Posted: November 4, 2015
• Study Start: January 1, 2016
• Primary Completion: February 1, 2020
• Study Completion: February 1, 2020
• Last Updated: February 17, 2020

Record last verified: 2020-02

Locations

DE (1)