Drug Interaction Between Paracetamol and Warfarin (INPAWA2)
This study has been completed.
Sponsor:
Hopital Lariboisière
Information provided by:
Hopital Lariboisière
ClinicalTrials.gov Identifier:
NCT01104337
First received: April 12, 2010
Last updated: April 13, 2010
Last verified: February 2010
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Purpose
The objective of this study is to investigate whether paracetamol, given at therapeutic doses (2g/day and 3 g/day), may potentiate the anticoagulant effect of warfarin.
| Condition | Intervention | Phase |
|---|---|---|
|
Deep Venous Thrombosis Pulmonary Embolism Atrial Fibrillation Stroke Antiphospholipid Syndrome |
Drug: paracetamol Drug: Placebo |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Screening |
| Official Title: | Dose-dependent Drug-drug Interaction Between Paracetamol and Warfarin in Adults Receiving Long-term Oral Anticoagulants: A Randomized Controlled Trial |
Resource links provided by NLM:
Genetics Home Reference related topics:
familial atrial fibrillation
MedlinePlus related topics:
Atrial Fibrillation
Blood Thinners
Deep Vein Thrombosis
Drug Reactions
Pulmonary Embolism
U.S. FDA Resources
Further study details as provided by Hopital Lariboisière:
Primary Outcome Measures:
- The mean maximum increase in INR from baseline to Day 10 (INR (max-D1)) [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- The mean maximum INR (INRmax) [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]
- The time to the first variation of INR observed [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]
- Day 10 - Day 1 differences in factors II, V, VII, AT-III plasma concentrations between groups. [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]
- Day 10 - Day 1 differences in paracetamol plasma concentration between groups. [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]
- Day 10 - Day 1 differences in R(-), S(-)warfarin plasma concentrations between groups. [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]
- Day 10 - Day 1 differences in Gla-type Osteocalcin (Gla-OC) and undercarboxylated Osteocalcin (Glu-OC)plasma concentrations between groups. [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]
- Relation between age and the mean maximum increase in INR from baseline to Day 10 (INR (max-D1) [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]Relation between age and INR (max-D1)is measured using regression analysis.
| Enrollment: | 45 |
| Study Start Date: | March 2007 |
| Study Completion Date: | February 2010 |
| Primary Completion Date: | November 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Paracetamol 2g/d
18 patients on stable warfarin therapy received a 10-day regimen of paracetamol 2g/d
|
Drug: paracetamol
Treatment consisted of two paracetamol 500mg (Doliprane® 500mg, Sanofi-aventis, Paris, France) tablets twice a day along with two matching placebo tablets once daily
|
|
Experimental: Paracetamol 3g/d
18 patients on stable warfarin therapy received a 10-day regimen of paracetamol 3g/d
|
Drug: paracetamol
Treatment consisted of two paracetamol 500mg (Doliprane® 500mg, Sanofi-aventis, Paris, France) tablets three times a day
|
|
Placebo Comparator: Placebo
9 patients on stable warfarin therapy received a 10-day regimen of placebo
|
Drug: Placebo
Treatment consisted of two matching placebo tablets three times a day.
|
Detailed Description:
Paracetamol is recommended as a first-line analgesic and antipyretic therapy in patients receiving short- and long-term oral anticoagulation, especially elderly patient.However,Increased INR was previously observed in patients treated with warfarin and paracetamol given at the maximum recommended dose (4g/day).
To date, the mechanism of this interaction has not been determined.A recent in vitro study suggested that the toxic metabolite N-acetyl-para-benzoquinoneimine (NAPQI) appeared to interfere with vitamin K-dependent γ-carboxylase (VKD-carb) and vitamin K epoxide reductase (VKOR) activites12. The question remaining to be dealt with is whether this in vitro observation can explain the in vivo paracetamol-warfarin interaction. We aim to evaluate the effect of paracetamol at the most widely used doses 2 and 3g/day on INR in stable patients treated with warfarin in a double blind randomized placebo-controlled trial and to identify the mechanism involved in this interaction in vivo.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Patients treated with warfarin (target INR 2 to 3) stable anticoagulation at 2 to 9 mg for more than 30 days
- Aged 18 years or older
- Laboratory values (hemoglobin, blood cell counts, albumin, blood ionogram, complementary hemostasis parameters and aspartate, alanine transaminases (AST and ALT))remained within normal limits
Exclusion Criteria:
- Any treatment change within 7 days before enrollment
- Any paracetamol intake within the last 14 days
- Drug allergy Concomitant drug ( 5-fluorouracile, acetylsalicylic acid, non steroidal anti-inflammatory drugs, chloramphenicol, diflunisal, miconazole)
- St John's wort treatment
- Pregnancy
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01104337
Locations
| France | |
| Therapeutic Research Unit, Department of Internal Medicine, Hospital Lariboière | |
| Paris, France, 75010 | |
Sponsors and Collaborators
Hopital Lariboisière
Investigators
| Principal Investigator: | Stephane Mouly, MD, PhD | Therapeutic Research Unit, Department of Internal Medicine, Hospital Lariboisière, Paris, France |
| Principal Investigator: | Guy Simoneau, MD | Therapeutic Research Unit, Department of Internal Medicine, Hospital Lariboisière, Paris, France |
More Information
No publications provided
| Responsible Party: | Pr Stephane Mouly, Therapeutic Research Unit, Department of Internal Medicine, Hospital Lariboisière, Paris,France |
| ClinicalTrials.gov Identifier: | NCT01104337 History of Changes |
| Other Study ID Numbers: | INPAWA2-URT |
| Study First Received: | April 12, 2010 |
| Last Updated: | April 13, 2010 |
| Health Authority: | France: Ministry of Health |
Keywords provided by Hopital Lariboisière:
|
paracetamol warfarin drug interaction pathogenic mechanism |
Additional relevant MeSH terms:
|
Atrial Fibrillation Embolism Pulmonary Embolism Stroke Thrombosis Venous Thrombosis Venous Thromboembolism Antiphospholipid Syndrome Arrhythmias, Cardiac Heart Diseases Cardiovascular Diseases Pathologic Processes Embolism and Thrombosis Vascular Diseases Lung Diseases |
Respiratory Tract Diseases Cerebrovascular Disorders Brain Diseases Central Nervous System Diseases Nervous System Diseases Thromboembolism Autoimmune Diseases Immune System Diseases Acetaminophen Warfarin Antipyretics Physiological Effects of Drugs Pharmacologic Actions Analgesics, Non-Narcotic Analgesics |
ClinicalTrials.gov processed this record on May 23, 2013