Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-clavulanic Acid

Atrial Fibrillation Clinical Trial

— INWARA  

Official title:

Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-clavulanic Acid

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00603317
• Other study ID #: P051056
• Status: Completed
• Phase: Phase 4
• First received: January 16, 2008
• Last updated: July 9, 2010
• Start date: March 2008
• Est. completion date: March 2010

Study information

• Verified date: May 2010
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: March 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrial Fibrillation
• Deep Venous Thrombosis
• Oral Anticoagulation
• Pulmonary Embolism
• Venous Thrombosis

Intervention

Drug:
• Firstly : Amoxicillin-Clavulanic acid and secondly : Placebo
Amoxicillin : 2g twice daily Clavulanic acid : 125 mg twice daily
• Firstly : Placebo and secondly : Amoxicillin-Clavulanic acid
Amoxicillin : 2g twice daily Clavulanic acid : 125mg twice daily seven consecutive days

Locations

Country	Name	City	State
France	Hopital Lariboisière - Service de médecine interne	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	INR at day one and seven (delta Day7-Day1)		7 days	Yes
Secondary	% 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	No