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

This study has been completed.
Sponsor:
Information provided by:
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00603317
First received: January 16, 2008
Last updated: July 9, 2010
Last verified: May 2010
History of Changes
  Purpose

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.


Condition Intervention Phase
Oral Anticoagulation
Deep Venous Thrombosis
Atrial Fibrillation
Pulmonary Embolism
 Drug: Firstly : Amoxicillin-Clavulanic acid and secondly : Placebo
Drug: Firstly : Placebo and secondly : Amoxicillin-Clavulanic acid
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-clavulanic Acid

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • INR at day one and seven (delta Day7-Day1) [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]

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 [ Time Frame: 7 days for each period ] [ Designated as safety issue: No ]

Enrollment: 13
Study Start Date: March 2008
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00603317

Locations
France
Hopital Lariboisière - Service de médecine interne
Paris, France, 75475
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Stephane MD MOULY, MD, PhD Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Valerie MILLUL, Department Clinical Reseach of Developpement
ClinicalTrials.gov Identifier: NCT00603317     History of Changes
Other Study ID Numbers: P051056
Study First Received: January 16, 2008
Last Updated: July 9, 2010
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Warfarin
Drug interaction
Pharmacogenetics
Amoxicillin
Clavulanic acid

Additional relevant MeSH terms:
Atrial Fibrillation
Embolism
Pulmonary Embolism
Thrombosis
Venous Thrombosis
Venous Thromboembolism
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Embolism and Thrombosis
Vascular Diseases
Lung Diseases
Respiratory Tract Diseases
 Thromboembolism
Amoxicillin
Clavulanic Acids
Clavulanic Acid
Amoxicillin-Potassium Clavulanate Combination
Warfarin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants
Hematologic Agents

ClinicalTrials.gov processed this record on May 23, 2013