Atrial FibrillationPhase 2DOSIDONCT01348074
Reinitiation of Anticoagulation After Temporary Withdrawal of Vitamin K Antagonist
A Phase 2 study testing Double dose in people with Atrial Fibrillation and Venous Thromboembolism, run by McMaster University at 1 site in Canada.
Trial summary
It is not known how to best restart warfarin after temporary withdrawal. Participants will be randomized to two groups. Group 1 will restart warfarin at their usual maintenance dose, group 2 will restart warfarin at double their maintenance dose for two days followed by their usual maintenance dose. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Atrial Fibrillation, Venous Thromboembolism, Heart Valve Disease
- What is being tested?
- Double dose
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 104 participants
- Where
- 1 siteCanada
- Study dates
- Apr 2011to Dec 2013
- Phase
- Phase 2
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Current treatment with warfarin
- Need for temporary interruption for invasive procedure or surgery
Who cannot join
- Need for post-operative hospitalization more than one day
- Participation in another clinical trial
- No consent given
Trial locations and contacts
1 site in 1 country.
Canada1 site
Thrombosis Service, HHS- General Hospital
Hamilton, Ontario, L8L 2X2
About this study
Official title: Phase II Study of Double Versus Single Reinitiation Dose of Warfarin After Interruption for Surgery
It is not known how to best restart warfarin after temporary withdrawal. Participants will be randomized to two groups. Group 1 will restart warfarin at their usual maintenance dose, group 2 will restart warfarin at double their maintenance dose for two days followed by their usual maintenance dose. The main outcome parameter will be the number of patients who are back in therapeutic INR (international normalized ratio) range 4, and 9 days after restarting anticoagulation with warfarin. Thromboembolic and/or bleeding events will be recorded as additional parameters. These data will be collected by a standardized telephone interview at 1 month. In addition, the investigators will evaluate a possible prothrombotic state by measuring the potential of thrombin generation and D-dimers in the subset of patients visiting HHS-General Hospital for their INR tests.
Read the detailed description
We will investigate if it is feasible to use double maintenance dose for the first two administrations of vitamin K antagonists when these drugs were temporarily interrupted and thus keep the time of an increased risk of thromboembolism and duration of "bridging" at a minimum. The control group will consist of patients who resume vitamin K antagonists at their usual maintenance dose. The aim of the study is to establish how to best restart anticoagulation with vitamin K antagonists after temporal withdrawal of these drugs. The main outcome parameter will be the proportion of patients who are back to a therapeutic international normalized ratio (INR) ratio at certain days after restarting vitamin K antagonists. Two additional parameters will be evaluated: Firstly, bleeding and thromboembolic complications will be reported and secondly, a possible prothrombotic state, measured as an elevation of D-dimer, at the initiation of anticoagulation will be evaluated.
- Being tested
- Double dose
- Keywords
- warfarin, surgery, management, thromboembolism, bleeding
- Medical subject headings
- Atrial Fibrillation, Venous Thromboembolism, Heart Valve Diseases, Thromboembolism, Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Double doseDrug
Also called Loading dose
For each individual the dose on Day 1 and Day 2 will be twice the one normally taken
| Study group | Role | What they receive |
|---|---|---|
| Double dose | Experimental | Re-initiation with warfarin at twice the usual maintenance dose the first 2 days, then maintenance dose. Receives: Drug: Double dose |
| Usual maintenance dose | No intervention | Usual maintenance dose from Day 1, i.e. no postoperative loading dose. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with INR back in therapeutic range Day 5 or Day 10
Proportion of patients with INR 2.0-3.0 on Day 5 or Day 10 (day of invasive procedure defined as Day 1)
Measured: Day 5-10
Secondary outcomes (4)
Thromboembolic events
Objectively verified arterial or venous thromboembolic events
Measured: 30 days
Major bleeding events
Defined by the ISTH criteria of 2010
Measured: 30 days
Minor bleeding events
Any bleeding requiring medical attention but not fulfilling the criteria of Major bleeding
Measured: 30 days
Laboratory parameters of hypercoagulability
Quantitative D-dimer and Thrombin Generation performed in a subset at day of procedure, day 5 and 10 to identify abnormal rise.
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 posted5 May 2011 (estimated)
- Study startApr 2011
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- More trials run by McMaster UniversityThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 104 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sam Schulman, McMaster University
- Investigators
- Sam Schulman, MD, PhD, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01348074
- Sponsor's protocol ID
- HGH20090520
- Acronym
- DOSIDO
- Status last verified
- Apr 2016
- First submitted
- 3 May 2011
- Last updated
- 5 Apr 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Schulman S, El Bouazzaoui B, Eikelboom JW, Zondag M. Clinical factors influencing the sensitivity to warfarin when restarted after surgery. J Intern Med. 2008 Apr;263(4):412-9. doi: 10.1111/j.1365-2796.2007.01913.x. Epub 2008 Jan 16.
PubMed 18205763Schulman S, Hwang HG, Eikelboom JW, Kearon C, Pai M, Delaney J. Loading dose vs. maintenance dose of warfarin for reinitiation after invasive procedures: a randomized trial. J Thromb Haemost. 2014 Aug;12(8):1254-9. doi: 10.1111/jth.12613. Epub 2014 Jun 25.
PubMed 24837794
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Double Versus Single Reinitiation Dose of Warfarin After Interruption for Surgery
- ClinicalTrials.gov ID
- NCT01348074
- Acronym / sponsor ID
- DOSIDO / HGH20090520
- Keywords
- warfarin, surgery, management, thromboembolism, bleeding
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 104 participants (actual)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Study start
- Apr 2011
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 5 May 2011 (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.
It is not known how to best restart warfarin after temporary withdrawal. Participants will be randomized to two groups. Group 1 will restart warfarin at their usual maintenance dose, group 2 will restart warfarin at double their maintenance dose for two days followed by their usual maintenance dose. The main outcome parameter will be the number of patients who are back in therapeutic INR (international normalized ratio) range 4, and 9 days after restarting anticoagulation with warfarin. Thromboembolic and/or bleeding events will be recorded as additional parameters. These data will be collected by a standardized telephone interview at 1 month. In addition, the investigators will evaluate a possible prothrombotic state by measuring the potential of thrombin generation and D-dimers in the subset of patients visiting HHS-General Hospital for their INR tests.
Detailed description
We will investigate if it is feasible to use double maintenance dose for the first two administrations of vitamin K antagonists when these drugs were temporarily interrupted and thus keep the time of an increased risk of thromboembolism and duration of "bridging" at a minimum. The control group will consist of patients who resume vitamin K antagonists at their usual maintenance dose. The aim of the study is to establish how to best restart anticoagulation with vitamin K antagonists after temporal withdrawal of these drugs. The main outcome parameter will be the proportion of patients who are back to a therapeutic international normalized ratio (INR) ratio at certain days after restarting vitamin K antagonists. Two additional parameters will be evaluated: Firstly, bleeding and thromboembolic complications will be reported and secondly, a possible prothrombotic state, measured as an elevation of D-dimer, at the initiation of anticoagulation will be evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Double dose | Experimental | Drug: Double doseRe-initiation with warfarin at twice the usual maintenance dose the first 2 days, then maintenance dose. |
| Usual maintenance dose | No intervention | –Usual maintenance dose from Day 1, i.e. no postoperative loading dose. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Current treatment with warfarin
- Need for temporary interruption for invasive procedure or surgery
Key exclusion criteria (3 listed)
- Need for post-operative hospitalization more than one day
- Participation in another clinical trial
- No consent given
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 |
|---|---|---|
| Double doseAlso: Loading doseFor each individual the dose on Day 1 and Day 2 will be twice the one normally taken | Drug | Double dose |
Primary outcome
Proportion of patients with INR back in therapeutic range Day 5 or Day 10
Time frame: Day 5-10
Proportion of patients with INR 2.0-3.0 on Day 5 or Day 10 (day of invasive procedure defined as Day 1)
4 secondary outcomes
Thromboembolic events
Time frame: 30 days
Major bleeding events
Time frame: 30 days
Minor bleeding events
Time frame: 30 days
Laboratory parameters of hypercoagulability
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 5 Apr 2016.
- Background: PubMed 18205763Schulman S, El Bouazzaoui B, Eikelboom JW, Zondag M. Clinical factors influencing the sensitivity to warfarin when restarted after surgery. J Intern Med. 2008 Apr;263(4):412-9. doi: 10.1111/j.1365-2796.2007.01913.x. Epub 2008 Jan 16.
- Results publication: PubMed 24837794Schulman S, Hwang HG, Eikelboom JW, Kearon C, Pai M, Delaney J. Loading dose vs. maintenance dose of warfarin for reinitiation after invasive procedures: a randomized trial. J Thromb Haemost. 2014 Aug;12(8):1254-9. doi: 10.1111/jth.12613. Epub 2014 Jun 25.
- Published article on this studyLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Sam Schulman, MD, PhD principal investigator
McMaster University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Double dose in people with Atrial Fibrillation and Venous Thromboembolism, run by McMaster University at 1 site in Canada.
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 2 inclusion and 3 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 5 Apr 2016. 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 Canada. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Proportion of patients with INR back in therapeutic range Day 5 or Day 10 (time frame: Day 5-10). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01348074, which also lists 2 linked publications.
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 5 Apr 2016; AzTrials last refreshed its copy on 8 Nov 2026.