Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-clavulanic Acid

Phase 4

Completed

• Conditions: Oral Anticoagulation; Deep Venous Thrombosis; Atrial Fibrillation; Pulmonary Embolism

• Registration Number: NCT00603317
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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

Study Timeline

• Study First Submitted: 2008-01-16
• Study First Submitted QC: 2008-01-16
• Study First Posted: 2008-01-29
• Study Start: 2008-03
• Primary Completion: 2010-03
• Study Completion: 2010-03
• Status Verified: 2010-05
• Last Update Submitted: 2010-07-09
• Last Update Posted: 2010-07-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
INR at day one and seven (delta Day7-Day1)	7 days

Secondary Outcome Measures

Name	Time	Method
% 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	7 days for each period

Trial Locations

Locations (1)

Hopital Lariboisière - Service de médecine interne; 🇫🇷 Paris, France