REduced Dose Versus Full-dose of Direct Oral Anticoagulant After uNprOvoked Venous thromboEmbolism.
RENOVE
1 other identifier
interventional
2,774
1 country
39
Brief Summary
Patients with unprovoked venous thromboembolism (VTE) or VTE associated with persistent risk factors have a high risk of recurrence after stopping anticoagulation. In these patients, international guidelines recommend indefinite anticoagulation. However, prolonged use of warfarin or DOAC at therapeutic dose is associated with a significant risk of bleeding. Consequently, it has been hypothesized that extended anticoagulation at lower dosage might be as effective as and safer than full dose of anticoagulation. However, low-dose warfarin (INR 1.5-2) was less effective and not safer than conventional dose warfarin (INR 2-3). Low dose of DOAC has the potential to validate this hypothesis. In a first randomized trial comparing full-dose or low-dose apixaban with a placebo during an additional one year of anticoagulation in patients where physicians were uncertain for prolonging anticoagulation ("Amplify-extension trial"), low-dose apixaban was more effective than placebo without any major concern regarding safety and possibly as effective as and safer than full-dose apixaban; in a second randomized trial comparing full-dose or low-dose rivaroxaban with aspirin, during an additional one year of anticoagulation in patients where physicians were uncertain for prolonging anticoagulation ("Einstein-Choice trial"), low-dose rivaroxaban was more effective than aspirin without any major concern regarding safety and possibly as effective as and safer than full-dose rivaroxaban. However, these two studies were not designed and powered to demonstrate non-inferiority on efficacy and superiority on safety of a reduced dose of DOAC versus a full dose DOAC and the selected population did not have strong indications for indefinite anticoagulation. Thus, there is currently no evidence to recommend a reduced dose rather than a full dose of DOAC for extended therapy in patients at high risk of recurrent VTE. Consequently, a randomized trial comparing low-dose DOAC with full-dose DOAC therapy in patients at high risk of recurrent VTE is needed and justified. Main hypothesis: After VTE at high risk of recurrence initially treated during 6 (-15 days) to 24 (+ 3 months) uninterrupted months, a reduced dose of DOAC will be non-inferior to a full dose of DOAC in terms of recurrent VTE during extended anticoagulation phase.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Nov 2017
Longer than P75 for phase_3
39 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
September 14, 2017
CompletedFirst Posted
Study publicly available on registry
September 18, 2017
CompletedStudy Start
First participant enrolled
November 2, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 8, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
November 8, 2023
CompletedDecember 28, 2023
December 1, 2023
6 years
September 14, 2017
December 22, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Recurrent VTE
Adjudicated symptomatic objectively confirmed recurrent VTE (non fatal or fatal VTE) during the study treatment period.
during a mean study treatment period of 36 months
Secondary Outcomes (6)
Major and clinically relevant non major bleeding
during a mean study treatment period of 36 months
The composite of recurrent VTE or major bleeding or non major clinically relevant bleeding
during a mean study treatment period of 36 months
Mortality
during a mean study treatment period of 36 months
Compliance
during a mean study treatment period of 36 months
Treatment effect
during a mean study treatment period of 36 months
- +1 more secondary outcomes
Study Arms (2)
Reduced dose of DOAC
EXPERIMENTALA reduced dose of DOAC (apixaban 2.5 mg twice daily or rivaroxaban 10 mg once daily) during a mean follow-up period of 36 months (12 to 65 months)
Full dose of DOAC
ACTIVE COMPARATORA full dose of DOAC (Apixaban 5 mg twice daily or Rivaroxaban 20 mg once daily) during a mean follow-up period of 36 months (12 to 65 months).
Interventions
The patient will receive apixaban 2.5 mg twice daily or rivaroxaban 10 mg once daily during a mean follow-up period of 36 months (12 to 65 months)
The patient will receive apixaban 5 mg twice daily or Rivaroxaban 20 mg once daily during a mean follow-up period of 36 months (12 to 65 months)
Eligibility Criteria
You may qualify if:
- Patients \>18 years
- Patients with indications for long-term anticoagulation after VTE (i.e.; symptomatic PE or proximal DVT) initially treated during 6 (-15 days) to 24 months (+ 3 months) :
- Patients with multiple episodes of VTE, or
- Patients with a first episode of unprovoked\* VTE
- Patients with VTE associated with persistent risk factor\*\*, or
- Patients for whom clinicians feel that indefinite anticoagulation is warranted
- Social security affiliation.
You may not qualify if:
- Known allergy to rivaroxaban and apixaban, allergy to any of the excipients
- Indication for therapeutic dose anticoagulant therapy
- Unable or refusal to give informed consent
- Isolated distal DVT
- HERDOO2 score ≤ 1
- Indication for anticoagulation other than DVT or PE (e.g.; atrial fibrillation, mechanic valves…)
- Treatment with investigational drug in the past 1 month except for patients benefiting from an anticoagulant at therapeutic doses for the initial pathology
- Chronic liver disease or chronic hepatitis
- Patient considered at high risk of bleeding (eg: previous gastro-intestinal tract bleeding in the past three months, uncontrolled hypertension, etc.)
- Renal insufficiency with creatinine \<25 ml / min on Cockcroft and Gault formula
- Antiphospholipid syndrome
- Dual anti-platelet therapy or aspirin at dosage \>100 mg per day
- 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 cancer of less than 6 months
- Active pregnancy or expected pregnancy
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University Hospital, Brestlead
- University Hospital of Saint-Etiennecollaborator
Study Sites (39)
CHU Amiens-Picardie
Amiens, 80054, France
CHU Angers
Angers, France
CH d'Arras
Arras, 62022, France
CHU de Besançon - Hôpital Jean Minjoz
Besançon, 25000, France
CH Bordeaux
Bordeaux, 33075, France
HIA Brest
Brest, 29240, France
CHRU de Brest
Brest, 29609, France
Clinique de Clapiers
Castelnau-le-Lez, 34170, France
HIA Percy
Clamart, 92141, France
Cabinet médical
Clapiers, 34830, France
CHU de Clermont Ferrand - Hôpital Gabriel Montpied
Clermont-Ferrand, 63003, France
APHP Hôpital Louis Mourier
Colombes, 92700, France
CHU de Dijon
Dijon, 21079, France
CHU de Grenoble - Hôpital Nord Michallon
Grenoble, 38700, France
GH Le Havre
Le Havre, 76290, France
CH Le Mans
Le Mans, 72 000, France
CHU de Limoges - Hôpital de Dupuytren
Limoges, 87042, France
CH Morlaix
Morlaix, 29 672, France
Chru Nancy
Nancy, 54511, France
CHU de Nantes
Nantes, 44000, France
CHU de Nice - Hôpital Pasteur
Nice, 06002, France
CHU Nîmes
Nîmes, 30 029, France
CHR Orléans
Orléans, 45100, France
Hôpital de Cochin
Paris, 75014, France
HEGP
Paris, 75015, France
CHU Paris Nord Val de Seine
Paris, 75018, France
HEGP
Paris, France
Kremlin Bicêtre
Paris, France
CH de Périgueux
Périgueux, 24019, France
CH de Quimper
Quimper, 29107, France
CHU de Rennes - Hôpital Sud
Rennes, 35203, France
CHU de ROUEN
Rouen, 76000, France
CH de Saint Brieuc - Hôpital Yves Le Foll
Saint-Brieuc, 22000, France
CHU de Saint Etienne - Hôpital Nord
Saint-Etienne, 42055, France
CH de Toulon - Hôpital Sainte-Musse
Toulon, 83056, France
HIA Sainte-Anne
Toulon, 83800, France
CHU de Toulouse - Hôpital de Rangueil
Toulouse, 31059, France
CHU de Tours - Hôpital Trousseau
Tours, 37170, France
CH Valenciennes
Valenciennes, 59 322, France
Related Publications (1)
Couturaud F, Schmidt J, Sanchez O, Ballerie A, Sevestre MA, Meneveau N, Bertoletti L, Connault J, Benhamou Y, Constans J, Quemeneur T, Lapebie FX, Pernod G, Picart G, Elias A, Doutrelon C, Neveux C, Khider L, Roy PM, Zuily S, Falvo N, Lacroix P, Emmerich J, Mahe I, Boileau J, Yaici A, Le Jeune S, Stephan D, Plissonneau-Duquene P, Ray V, des Deserts MD, Belhadj-Chaidi R, Lamia B, Gruel Y, Presles E, Girard P, Tromeur C, Moustafa F, Rothstein V, Lacut K, Melac S, Barillot S, Mismetti P, Laporte S, Mottier D, Meyer G, Leroyer C; RENOVE Investigators. Extended treatment of venous thromboembolism with reduced-dose versus full-dose direct oral anticoagulants in patients at high risk of recurrence: a non-inferiority, multicentre, randomised, open-label, blinded endpoint trial. Lancet. 2025 Mar 1;405(10480):725-735. doi: 10.1016/S0140-6736(24)02842-3.
PMID: 40023651DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 14, 2017
First Posted
September 18, 2017
Study Start
November 2, 2017
Primary Completion
November 8, 2023
Study Completion
November 8, 2023
Last Updated
December 28, 2023
Record last verified: 2023-12
Data Sharing
- IPD Sharing
- Will not share