Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-Clavulanic Acid - Full Text View

Sponsored by:	Assistance Publique - Hôpitaux de Paris
Information provided by:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT00603317

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 IV

Genetics Home Reference related topics: Brugada syndrome familial atrial fibrillation short QT syndrome

MedlinePlus related topics: Blood Thinners Deep Vein Thrombosis Pulmonary Embolism

Drug Information available for: Warfarin Warfarin potassium Warfarin sodium Amoxicillin Amoxicillin sodium Amoxicillin trihydrate Amoxicillin-potassium clavulanate combination Clavulanic acid

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Pharmacodynamics Study
Official Title:	Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-Clavulanic Acid

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 ]

Estimated Enrollment:	12
Study Start Date:	March 2008
Estimated Study Completion Date:	September 2009
Estimated Primary Completion Date:	September 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental 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
2: Experimental 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

Responsible Party:	Department Clinical Reseach of Developpement ( Valerie MILLUL )
Study ID Numbers:	P051056, EUDRACT 2006-003432-30, CRC 05 111, AFSSAPS A70644-3T
Study First Received:	January 16, 2008
Last Updated:	September 5, 2008
ClinicalTrials.gov Identifier:	NCT00603317
Health Authority:	France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:

Warfarin
Drug interaction
Pharmacogenetics
Amoxicillin
Clavulanic acid

Study placed in the following topic categories:

Amoxicillin
Pulmonary Embolism
Heart Diseases
Vascular Diseases
Clavulanic Acids
Warfarin
Amoxicillin-Potassium Clavulanate Combination
Thrombosis

Embolism and Thrombosis
Respiratory Tract Diseases
Embolism
Clavulanic Acid
Lung Diseases
Venous Thrombosis
Atrial Fibrillation
Arrhythmias, Cardiac

Additional relevant MeSH terms:

Anti-Infective Agents
Anti-Bacterial Agents
Anticoagulants
Pathologic Processes
Molecular Mechanisms of Pharmacological Action

Therapeutic Uses
Hematologic Agents
Enzyme Inhibitors
Cardiovascular Diseases
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009