Clinical trial NCT00603317: Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-clavulanic Acid
Official title: Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-clavulanic Acid
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Oral Anticoagulation
Deep Venous Thrombosis
Atrial Fibrillation
Pulmonary Embolism
Keywords: Warfarin
Drug interaction
Pharmacogenetics
Amoxicillin
Clavulanic acid
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2008-01-29
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: INR at day one and seven (delta Day7-Day1)
timeFrame: 7 days
Secondary outcomes:
measure: % 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
timeFrame: 7 days for each period
Other outcomes:
Locations:
city: Paris
country: France
facility: Hopital Lariboisière - Service de médecine interne
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Stephane MD MOULY, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: