Deep Venous ThrombosisPhase 4INPAWA2NCT01104337
Drug Interaction Between Paracetamol and Warfarin
A Phase 4 study testing paracetamol in people with Deep Venous Thrombosis and Pulmonary Embolism, run by Hopital Lariboisière at 1 site in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Deep Venous Thrombosis, Pulmonary Embolism, Atrial Fibrillation
- What is being tested?
- paracetamol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteFrance
- Study dates
- Mar 2007to Feb 2010
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
France1 site
Therapeutic Research Unit, Department of Internal Medicine, Hospital Lariboière
Paris, 75010
About this study
Official title: Dose-dependent Drug-drug Interaction Between Paracetamol and Warfarin in Adults Receiving Long-term Oral Anticoagulants: A Randomized Controlled Trial
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.
Read the 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.
- Conditions
- Deep Venous Thrombosis, Pulmonary Embolism, Atrial Fibrillation, Stroke, Antiphospholipid Syndrome
- Being tested
- paracetamol, Placebo
- Keywords
- paracetamol, warfarin, drug interaction, pathogenic mechanism
- Medical subject headings
- Venous Thrombosis, Pulmonary Embolism, Atrial Fibrillation, Stroke, Antiphospholipid Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
paracetamolDrug
Treatment consisted of two paracetamol 500mg (Doliprane® 500mg, Sanofi-aventis, Paris, France) tablets twice a day along with two matching placebo tablets once daily
paracetamolDrug
Treatment consisted of two paracetamol 500mg (Doliprane® 500mg, Sanofi-aventis, Paris, France) tablets three times a day
PlaceboDrug
Treatment consisted of two matching placebo tablets three times a day.
| Study group | Role | What they receive |
|---|---|---|
| Paracetamol 2g/d | Experimental | 18 patients on stable warfarin therapy received a 10-day regimen of paracetamol 2g/d Receives: Drug: paracetamol |
| Paracetamol 3g/d | Experimental | 18 patients on stable warfarin therapy received a 10-day regimen of paracetamol 3g/d Receives: Drug: paracetamol |
| Placebo | Placebo comparator | 9 patients on stable warfarin therapy received a 10-day regimen of placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The mean maximum increase in INR from baseline to Day 10 (INR (max-D1))
Measured: 10 days
Secondary outcomes (7)
The mean maximum INR (INRmax)
Measured: 10 days
The time to the first variation of INR observed
Measured: 10 days
Day 10 - Day 1 differences in factors II, V, VII, AT-III plasma concentrations between groups.
Measured: 10 days
Day 10 - Day 1 differences in paracetamol plasma concentration between groups.
Measured: 10 days
Day 10 - Day 1 differences in R(-), S(-)warfarin plasma concentrations between groups.
Measured: 10 days
Day 10 - Day 1 differences in Gla-type Osteocalcin (Gla-OC) and undercarboxylated Osteocalcin (Glu-OC)plasma concentrations between groups.
Measured: 10 days
Relation between age and the mean maximum increase in INR from baseline to Day 10 (INR (max-D1)
Relation between age and INR (max-D1)is measured using regression analysis.
Measured: 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2010 (estimated)
- Study startMar 2007
- Primary completionNov 2008
- Study completionFeb 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Deep Venous ThrombosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hopital Lariboisière
- Sponsor type
- University, hospital or other
- Investigators
- Stephane Mouly, MD, PhD, Principal investigator, Therapeutic Research Unit, Department of Internal Medicine, Hospital Lariboisière, Paris, FranceGuy Simoneau, MD, Principal investigator, Therapeutic Research Unit, Department of Internal Medicine, Hospital Lariboisière, Paris, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01104337
- Sponsor's protocol ID
- INPAWA2-URT
- Acronym
- INPAWA2
- Status last verified
- Feb 2010
- First submitted
- 12 Apr 2010
- Last updated
- 15 Apr 2010
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose-dependent Drug-drug Interaction Between Paracetamol and Warfarin in Adults Receiving Long-term Oral Anticoagulants: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT01104337
- Acronym / sponsor ID
- INPAWA2 / INPAWA2-URT
- Conditions
- Deep Venous Thrombosis, Pulmonary Embolism, Atrial Fibrillation, Stroke, Antiphospholipid Syndrome
- Keywords
- paracetamol, warfarin, drug interaction, pathogenic mechanism
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Hopital LariboisièreUniversity, hospital or other
- Study start
- Mar 2007
- Primary completion
- Nov 2008 (actual)
- Study completion
- Feb 2010 (actual)
- First posted
- 15 Apr 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Paracetamol 2g/d | Experimental | Drug: paracetamol18 patients on stable warfarin therapy received a 10-day regimen of paracetamol 2g/d |
| Paracetamol 3g/d | Experimental | Drug: paracetamol18 patients on stable warfarin therapy received a 10-day regimen of paracetamol 3g/d |
| Placebo | Placebo comparator | Drug: Placebo9 patients on stable warfarin therapy received a 10-day regimen of placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| paracetamolTreatment consisted of two paracetamol 500mg (Doliprane® 500mg, Sanofi-aventis, Paris, France) tablets twice a day along with two matching placebo tablets once daily | Drug | Paracetamol 2g/d |
| paracetamolTreatment consisted of two paracetamol 500mg (Doliprane® 500mg, Sanofi-aventis, Paris, France) tablets three times a day | Drug | Paracetamol 3g/d |
| PlaceboTreatment consisted of two matching placebo tablets three times a day. | Drug | Placebo |
Primary outcome
The mean maximum increase in INR from baseline to Day 10 (INR (max-D1))
Time frame: 10 days
7 secondary outcomes
The mean maximum INR (INRmax)
Time frame: 10 days
The time to the first variation of INR observed
Time frame: 10 days
Day 10 - Day 1 differences in factors II, V, VII, AT-III plasma concentrations between groups.
Time frame: 10 days
Day 10 - Day 1 differences in paracetamol plasma concentration between groups.
Time frame: 10 days
Day 10 - Day 1 differences in R(-), S(-)warfarin plasma concentrations between groups.
Time frame: 10 days
Day 10 - Day 1 differences in Gla-type Osteocalcin (Gla-OC) and undercarboxylated Osteocalcin (Glu-OC)plasma concentrations between groups.
Time frame: 10 days
Relation between age and the mean maximum increase in INR from baseline to Day 10 (INR (max-D1)
Time frame: 10 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2010.
Related trials for Deep Venous Thrombosis
Enrolling by invitationObservational study
ClotTriever® Thrombectomy System Use-Result Survey in Japan
Deep Vein Thrombosis
Not yet recruiting
SAFELY RULING OUT DEEP VEIN THROMBOSIS IN PREGNANCY WITH THE LEFt SCORE AND TRIMESTER-ADJUSTED D-DIMER CUTOFFS (the PREG-DVT Study): A PROSPECTIVE COHORT STUDY.
Pregnancy Related, Deep Vein Thrombosis
RecruitingObservational study
Cleaner Long-tErm Assessment Registry - Venous Insights and Efficacy With eXtended Tracking
Deep Vein Thrombosis (DVT), Thrombus in the Peripheral Venous Vasculature
Enrolling by invitation
Evaluating the Use of Grip Exercises to Decrease Deep Vein Thrombosis in Adult Patients With PICC Lines
Deep Vein Thrombosis
Recruiting
PROfunda Femoris Vein Thrombosis Evaluation and Clearance to Improve Outcomes of Endovascular Treatment for Acute Iliofemoral Deep Vein Thrombosis
Deep Vein Thrombosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephane Mouly, MD, PhD principal investigator
Therapeutic Research Unit, Department of Internal Medicine, Hospital Lariboisière, Paris, France
Guy Simoneau, MD principal investigator
Therapeutic Research Unit, Department of Internal Medicine, Hospital Lariboisière, Paris, France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing paracetamol in people with Deep Venous Thrombosis and Pulmonary Embolism, run by Hopital Lariboisière at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Apr 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The mean maximum increase in INR from baseline to Day 10 (INR (max-D1)) (time frame: 10 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2010; AzTrials last refreshed its copy on 29 Oct 2026.