Oral AnticoagulationPhase 4INWARANCT00603317
Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-clavulanic Acid
A Phase 4 study of Oral Anticoagulation and Deep Venous Thrombosis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Oral Anticoagulation, Deep Venous Thrombosis, Atrial Fibrillation
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 1 siteFrance
- Study dates
- Mar 2008to Mar 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 to 80 years
- 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 (3 consecutive INR in the target)
- stable dose
- no infection
- normal CRP
- age >18 years
- normal transaminase levels
Who cannot join
- drug allergy
- penicillin allergy
- Alzheimer
- cancer
- thyroid disease
- gastro intestinal chronic disease
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- Firstly : Amoxicillin-Clavulanic acid and secondly : Placebo, Firstly : Placebo and secondly : Amoxicillin-Clavulanic acid
- Keywords
- Warfarin, Drug interaction, Pharmacogenetics, Amoxicillin, Clavulanic acid
- Medical subject headings
- Venous Thrombosis, Atrial Fibrillation, Pulmonary Embolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Firstly : Amoxicillin-Clavulanic acid and secondly : PlaceboDrug
Amoxicillin : 2g twice daily Clavulanic acid : 125 mg twice daily
Firstly : Placebo and secondly : Amoxicillin-Clavulanic acidDrug
Amoxicillin : 2g twice daily Clavulanic acid : 125mg twice daily seven consecutive days
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Order 1 : Firstly Amoxicillin-Acid clavulanic, and Secondly Placebo Receives: Drug: Firstly : Amoxicillin-Clavulanic acid and secondly : Placebo |
| 2 | Experimental | Order 2 : Firstly Placebo, and Secondly Amoxicillin-Acid clavulanic Receives: Drug: Firstly : Placebo and secondly : Amoxicillin-Clavulanic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
INR at day one and seven (delta Day7-Day1)
Measured: 7 days
Secondary outcomes (1)
% 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
Measured: 7 days for each period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2008 (estimated)
- Study startMar 2008
- Primary completionMar 2010
- Study completionMar 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Oral AnticoagulationStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Investigators
- Stephane MD MOULY, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00603317
- Sponsor's protocol ID
- P051056
- Acronym
- INWARA
- Status last verified
- May 2010
- First submitted
- 16 Jan 2008
- Last updated
- 12 Jul 2010
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-clavulanic Acid
- ClinicalTrials.gov ID
- NCT00603317
- Acronym / sponsor ID
- INWARA / P051056
- Keywords
- Warfarin, Drug interaction, Pharmacogenetics, Amoxicillin, Clavulanic acid
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Mar 2008
- Primary completion
- Mar 2010 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 29 Jan 2008 (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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Firstly : Amoxicillin-Clavulanic acid and secondly : PlaceboOrder 1 : Firstly Amoxicillin-Acid clavulanic, and Secondly Placebo |
| 2 | Experimental | Drug: Firstly : Placebo and secondly : Amoxicillin-Clavulanic acidOrder 2 : Firstly Placebo, and Secondly Amoxicillin-Acid clavulanic |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- patients treated with warfarin (target INR 2 to 3)
- stable anticoagulation (3 consecutive INR in the target)
- stable dose
- no infection
- normal CRP
Key exclusion criteria (15 listed)
- drug allergy
- penicillin allergy
- Alzheimer
- cancer
- thyroid disease
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 |
|---|---|---|
| Firstly : Amoxicillin-Clavulanic acid and secondly : PlaceboAmoxicillin : 2g twice daily Clavulanic acid : 125 mg twice daily | Drug | 1 |
| Firstly : Placebo and secondly : Amoxicillin-Clavulanic acidAmoxicillin : 2g twice daily Clavulanic acid : 125mg twice daily seven consecutive days | Drug | 2 |
Primary outcome
INR at day one and seven (delta Day7-Day1)
Time frame: 7 days
1 secondary outcome
% 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
Time frame: 7 days for each period
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 12 Jul 2010.
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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 MD MOULY, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
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 of Oral Anticoagulation and Deep Venous Thrombosis, run by Assistance Publique - Hôpitaux de Paris 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 7 inclusion and 15 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 12 Jul 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. 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?
INR at day one and seven (delta Day7-Day1) (time frame: 7 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 12 Jul 2010.