Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-clavulanic Acid (INWARA)

July 9, 2010 updated by: Assistance Publique - Hôpitaux de Paris

Several case reports indicate that the use of the antibiotic combination amoxicillin and clavulanic acid (AM-CLAVAC) can interact with warfarin pharmacodynamics. However, fever per se might also be responsible of these warfarin overdose reports, as well as the use of high dose paracetamol.

The aim of the present study is to determine if AM-CLAVAC can increase the pharmacodynamics of warfarin among patients at steady state Double blinded cross over controlled study vs placebo performed in 12 evaluable patients treated with warfarin with an INR target 2 to 3 and a stable INR and a stable dose.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Double blinded cross over controlled study vs placebo performed in 12 evaluable patients treated with warfarin with an INR target 2 to 3 and a stable INR and a stable dose

One period : seven consecutive days of amoxicillin(2g twice daily)- clavulanic acid (125 mg twice daily) association Wash out period of at least 4 weak with the return to a stable INR and warfarin dose One period : seven consecutive days of placebo twice daily

Main outcome INR delta Day7-Day

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75475
        • Hopital Lariboisière - Service de médecine interne

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • patients treated with warfarin (target INR 2 to 3)
  • stable anticoagulation (3 consecutive INR in the target)
  • stable dose
  • no infection
  • normal CRP
  • age >18 years
  • normal transaminase levels

Exclusion Criteria:

  • drug allergy
  • penicillin allergy
  • Alzheimer
  • cancer
  • thyroid disease
  • gastro intestinal chronic disease
  • frequent nausea or vomiting
  • Cirrhosis
  • chronic renal failure (GFR<60 ml/min)
  • frequent intake of paracetamol or NSAID
  • addict to drugs or alcool
  • St John's wort treatment or grapefruit juice intake
  • concomitant drugs (amiodarone, cimetidine, SSRI, clofibrate, fenofibrate, diltiazem, fluconazole, itraconazole, isoniazide, voriconazole, métronidazole, miconazole , omeprazole, glucocorticoids, zileuton, ritonavir, rifampicin, carbamazepine, phenytoin, phenobarbital)
  • antibiotic use during the 3 last weeks
  • pregnancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Order 1 : Firstly Amoxicillin-Acid clavulanic, and Secondly Placebo
Drug: Firstly : Amoxicillin-Clavulanic acid and secondly : Placebo
Amoxicillin : 2g twice daily Clavulanic acid : 125 mg twice daily
Experimental: 2
Order 2 : Firstly Placebo, and Secondly Amoxicillin-Acid clavulanic
Drug: Firstly : Placebo and secondly : Amoxicillin-Clavulanic acid
Amoxicillin : 2g twice daily Clavulanic acid : 125mg twice daily seven consecutive days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
INR at day one and seven (delta Day7-Day1)
Time Frame: 7 days
7 days

Secondary Outcome Measures

Outcome Measure
Time Frame
% of patients with an INR>3.5 during each study period mean INR during each study period effect of VKORC1 genetic polymorphism trough blood concentrations of S and R warfarin at day1 and day7 (delta) during each study period
Time Frame: 7 days for each period
7 days for each period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Stephane MD MOULY, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2008

Primary Completion (Actual)

March 1, 2010

Study Completion (Actual)

March 1, 2010

Study Registration Dates

First Submitted

January 16, 2008

First Submitted That Met QC Criteria

January 16, 2008

First Posted (Estimate)

January 29, 2008

Study Record Updates

Last Update Posted (Estimate)

July 12, 2010

Last Update Submitted That Met QC Criteria

July 9, 2010

Last Verified

May 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P051056

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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