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

Primary Purpose

Oral Anticoagulation, Deep Venous Thrombosis, Atrial Fibrillation

Status
Completed
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
Firstly : Amoxicillin-Clavulanic acid and secondly : Placebo
Firstly : Placebo and secondly : Amoxicillin-Clavulanic acid
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Oral Anticoagulation focused on measuring Warfarin, Drug interaction, Pharmacogenetics, Amoxicillin, Clavulanic acid

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hopital Lariboisière - Service de médecine interne

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

1

2

Arm Description

Order 1 : Firstly Amoxicillin-Acid clavulanic, and Secondly Placebo

Order 2 : Firstly Placebo, and Secondly Amoxicillin-Acid clavulanic

Outcomes

Primary Outcome Measures

INR at day one and seven (delta Day7-Day1)

Secondary Outcome Measures

% 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

Full Information

First Posted
January 16, 2008
Last Updated
July 9, 2010
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT00603317
Brief Title
Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-clavulanic Acid
Acronym
INWARA
Official Title
Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-clavulanic Acid
Study Type
Interventional

2. Study Status

Record Verification Date
May 2010
Overall Recruitment Status
Completed
Study Start Date
March 2008 (undefined)
Primary Completion Date
March 2010 (Actual)
Study Completion Date
March 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oral Anticoagulation, Deep Venous Thrombosis, Atrial Fibrillation, Pulmonary Embolism
Keywords
Warfarin, Drug interaction, Pharmacogenetics, Amoxicillin, Clavulanic acid

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Order 1 : Firstly Amoxicillin-Acid clavulanic, and Secondly Placebo
Arm Title
2
Arm Type
Experimental
Arm Description
Order 2 : Firstly Placebo, and Secondly Amoxicillin-Acid clavulanic
Intervention Type
Drug
Intervention Name(s)
Firstly : Amoxicillin-Clavulanic acid and secondly : Placebo
Intervention Description
Amoxicillin : 2g twice daily Clavulanic acid : 125 mg twice daily
Intervention Type
Drug
Intervention Name(s)
Firstly : Placebo and secondly : Amoxicillin-Clavulanic acid
Intervention Description
Amoxicillin : 2g twice daily Clavulanic acid : 125mg twice daily seven consecutive days
Primary Outcome Measure Information:
Title
INR at day one and seven (delta Day7-Day1)
Time Frame
7 days
Secondary Outcome Measure Information:
Title
% 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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephane MD MOULY, MD, PhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hopital Lariboisière - Service de médecine interne
City
Paris
ZIP/Postal Code
75475
Country
France

12. IPD Sharing Statement

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Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-clavulanic Acid

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