Study Stopped
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Venous Thromboembolism in Renally Impaired Patients and Direct Oral Anticoagulants
VERDICT
2 other identifiers
interventional
203
1 country
31
Brief Summary
In renally impaired patients with acute venous thromboembolism (VTE), standard-of-care (SOC) anticoagulation, i.e. heparins-vitamin K antagonists (VKA), at therapeutic dosage is associated with an increased risk of thromboembolic and bleeding complications compared to patients with normal renal function. Direct oral anticoagulants (DOAs) have been shown to be at least as effective and safe as SOC in VTE treatment. But in the clinical trials, moderate renally impaired patients were poorly represented and patients with severe renal insufficiency not at all. So no dose reduction was considered. Surprisingly, DOAs have been approved for VTE treatment in moderate and severe renally impaired patients. There is need to evaluate a reduced dose of DOAs for VTE treatment in patients with moderate and severe renal insufficiency. We plan to evaluate reduced doses of 2 DOAs (apixaban, rivaroxaban) compared to SOC in VTE patients with moderate or severe renal insufficiency in terms of net clinical benefit (recurrent VTE and major bleeding) at 3 months.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Oct 2016
Longer than P75 for phase_3
31 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 22, 2016
CompletedFirst Posted
Study publicly available on registry
January 26, 2016
CompletedStudy Start
First participant enrolled
October 19, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 30, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
May 30, 2022
CompletedOctober 19, 2022
October 1, 2022
5.1 years
January 22, 2016
October 17, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Non inferiority of reduced doses of DOAs
To demonstrate that reduced doses of DOAs (rivaroxaban or apixaban) are non-inferior to standard of care (heparins/VKA) on the net clinical benefit (recurrent VTE and major bleeding) in renally impaired patients suffering from an acute VTE.
Month 3
Secondary Outcomes (2)
Bleeding events
Month 3
Venous Thromboembolism (VTE) events
Month 3
Study Arms (2)
DOA : Direct Oral Anticoagulants
EXPERIMENTALThe experimental group receiving DOA regimens: patients will be secondarily randomly assigned within DOAs group between: * Apixaban (Eliquis® tablet) 10 mg bid for 7 days then 2.5 mg bid for 3 months * Rivaroxaban (Xarelto® tablet) 15 mg bid for 21 days then 15 mg od for 3 months.
SOC : Standard Of Care
ACTIVE COMPARATORThe control group receiving the standard of care (SOC), i.e. heparins/VKA regimen. Patients will receive the current recommended therapy: subcutaneous or intravenous UFH/VKA in case of severe renal insufficiency and subcutaneous LMWH/VKA in case of moderate renal insufficiency for at least 5 days. VKA will begin concomitantly and continue for 3 months.
Interventions
Eligibility Criteria
You may qualify if:
- Patients with a moderate renal insufficiency defined by a creatinine clearance between 30 to 50 ml/min (Cockcroft and Gault formulae) or a severe renal insufficiency (between 15 to 29 ml/min)
- Patients with acute objectively confirmed symptomatic proximal deep-vein thrombosis (DVT) or pulmonary embolism (PE) (with or without deep-vein thrombosis), planned to be treated for at least 3 months
- Patients \>18 years
- Life expectancy more than 3 months
- Social security affiliation
- Signed informed consent
You may not qualify if:
- Indication for anticoagulants other than VTE
- Active bleeding or a high risk of bleeding contraindicating anticoagulant treatment; a systolic blood pressure of more than 180 mm Hg or a diastolic blood pressure of more than 110 mm Hg
- Anticoagulation for more than 72 hours prior to randomization
- Chronic liver disease or chronic hepatitis
- Patient at high risk of bleeding
- Creatinine clearance \<15 ml/min or end stage renal disease or indication for extra-renal dialysis
- Need for concomitant anti-platelet therapy other than aspirin 75-325 mg per day. However concomitant treatment with aspirin is discouraged in this population at bleeding risk.
- Concomitant use of a strong inhibitor of cytochrome P-450 3A4 (CYP3A4) (e.g., a protease inhibitor for human immunodeficiency virus infection or azole-antimycotics agents ketoconazole, itraconazole, voriconazole, posaconazole) or a CYP3A4 inducer (e.g., rifampin, carbamazepine, or phenytoin),
- Active pregnancy or expected pregnancy or no effective contraception
- Any contraindication listed in the local labeling of UFH, LMWH or VKA or oral anticoagulant.
- Cancer-associated VTE requiring long-term treatment with LMWH
- Life expectancy of less than 3 months.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (31)
CH ARRAS
Arras, Boulevard Georges Besnier, 62022, France
Chu Tours
Tours, Hôpital Trousseau, 37550, France
CH d'Agen-Nérac
Agen, France
Chu Amiens
Amiens, 80054, France
Chu Angers
Angers, 49933, France
CH Besançon
Besançon, 25030, France
CHU de Bordeaux
Bordeaux, France
CHU La Cavale Blanche Brest
Brest, 29200, France
HIA de Brest
Brest, France
CHU Castelnau-le-Lez
Castelnau-le-Lez, 34170, France
CH Louis Pasteur - Chartres
Chartres, France
Chu Clermont-Ferrand
Clermont-Ferrand, 63003, France
CHU Dijon
Dijon, 21034, France
Hôpital La Tronche Grenoble
Grenoble, 38043, France
Hôpital Charles Foix - APHP Ivry sur Seine
Ivry-sur-Seine, 94200, France
Chu Limoges
Limoges, 87000, France
CHU Lyon
Lyon, 69000, France
HCL - Hôpital Edouard Herriot
Lyon, France
Chu Montpellier
Montpellier, 34295, France
CHU de Nantes - Hôpital Bellier
Nantes, France
CHU de Nantes - Hôpital Hôtel Dieu
Nantes, France
CHU Nice
Nice, 06003, France
HEGP - APHP Paris
Paris, 75000, France
Hôpital Louis Mourier- APHP Paris
Paris, 75000, France
CHU de Rouen
Rouen, France
Chu Saint Etienne
Saint-Etienne, 42055, France
Chu Strasbourg
Strasbourg, 67091, France
CH Toulon
Toulon, 83056, France
HIA de Toulon
Toulon, France
CHU Toulouse
Toulouse, 31059, France
CH de Valenciennes
Valenciennes, France
Related Publications (1)
Wetmore JB, Herzog CA, Yan H, Reyes JL, Weinhandl ED, Roetker NS. Apixaban versus Warfarin for Treatment of Venous Thromboembolism in Patients Receiving Long-Term Dialysis. Clin J Am Soc Nephrol. 2022 May;17(5):693-702. doi: 10.2215/CJN.14021021. Epub 2022 Apr 25.
PMID: 35470214DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
MISMETTI Patrick, MD
CHU SAINT-ETIENNE
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 22, 2016
First Posted
January 26, 2016
Study Start
October 19, 2016
Primary Completion
November 30, 2021
Study Completion
May 30, 2022
Last Updated
October 19, 2022
Record last verified: 2022-10
Data Sharing
- IPD Sharing
- Will not share