Venous Thromboembolism in Renally Impaired Patients and Direct Oral Anticoagulants

  • STATUS
    Recruiting
  • End date
    Jun 26, 2022
  • participants needed
    800
  • sponsor
    Centre Hospitalier Universitaire de Saint Etienne
Updated on 26 January 2021
heparin
renal function
anticoagulants
renal failure
rivaroxaban
vitamins
anticoagulant
renal function test
vitamin k antagonists

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.

Description

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. These patients represent more than 20% of the VTE population in clinical practice. 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 (<10%) and patients with severe renal insufficiency not at all. So no dose reduction was considered.

The new DOAs have also been developed for stroke prevention in atrial fibrillation (SPAF). Patients including in AF trials are generally older and more prone to present renal impairment (>20%) than in VTE trials. So a reduced dose of DOAs was evaluated and shown to be at least as effective as, and safer than VKA in the subgroup of patients with moderate renal insufficiency (creatinine clearance between 30 to 50 ml/min).

Surprisingly, DOAs have been approved for VTE treatment and SPAF in moderate and severe renally impaired patients (creatinine clearance between 15 to 30 mL/min). Moreover, patients have to receive a reduced dose of DOAs for SPAF but a full dose of DOAs for VTE that could be associated with an increased bleeding risk, as suggested by some subgroup analyses. So, there, there is need to evaluate a reduced dose of DOAs for VTE treatment in patients with moderate and severe renal insufficiency (creatinine clearance between 15 to 50 mL/min).

Apixaban and rivaroxaban appear to be the best candidates since:

  • both are approved in France in VTE patients
  • they have mixed pathway of elimination (hepatic and renal)
  • they have several other pharmacological similarities and they respective clinical trials have shown similar efficacy and safety profiles when compared with SOC for VTE treatment.
  • they do not need to be preceded by initial parenteral heparins on the contrary to dabigatran and edoxaban. This allows evaluating the impact of DOAs in renally impaired patients independently from the initial heparins effect
  • a reduced dose regimen is available and approved in AF
  • the evaluation of 2 DAOs allows evaluating the concept of this new class in renally impaired VTE patients independently from the pharmaceutical companies.

Finally 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.

Details
Condition Renal Failure, Nephropathy, Kidney Disease (Pediatric), Renal Impairment, Renal Dysfunction, Impaired Renal Function, Kidney Failure (Pediatric), Kidney Disease, Kidney Failure, kidney insufficiency, renal insufficiency
Treatment Rivaroxaban, heparin, Apixaban, VKA
Clinical Study IdentifierNCT02664155
SponsorCentre Hospitalier Universitaire de Saint Etienne
Last Modified on26 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have any of these conditions: Kidney Disease or Renal Failure or Kidney Failure (Pediatric) or Kidney Disease (Pediatric) or Kidney Failure or Nephropathy?
Do you have any of these conditions: kidney insufficiency or Impaired Renal Function or Renal Impairment or Nephropathy or Kidney Failure or Kidney Disease (Pediatric) or Renal Dysfunctio...?
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

Exclusion Criteria

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
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

Phone Email

0/250
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note