Anticoagulants; IncreasedPhase 3NCT04891861
Restart TICrH Alpha Pilot Protocol, Restarting DOACs After Traumatic Intracranial Hemorrhage
A Phase 3 study testing Apixaban in people with Anticoagulants; Increased, run by University of Texas at Austin.
Trial summary
Randomized pilot trial of restarting DOACs at 1 week versus 4 weeks after traumatic intracranial hemorrhage Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- Anticoagulants; Increased
- What is being tested?
- Apixaban
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- 1 Jul 2021to 1 Jul 2023
- Phase
- Phase 3
- 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 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Acute traumatic intracranial hemorrhage on anticoagulation for Atrial Fibrillation (AF) or Venous Thromboembolism (VTE)
- Patient is higher risk for stroke or other thrombotic events as witnessed by having a CHA2DS2-VASc score of > 3 (at least 3 of the following risk factors: age greater than 65, (age > 75 counts for 2 points), history of stroke or TIA (2 points), history of heart failure, history of diabetes, history of atherosclerotic vascular disease, female biological sex, history of hypertension)
- DOAC prescribed at label dose with creatinine clearance adjustments. DOAC at continuation dose, i.e., not initial therapy high doses in the setting of VTE
Who cannot join
- Mechanical Valve or Ventricular Assist Device (VAD)
- SDH >8 mm maximum width or any midline shift at any time point or more than one SDH
- Physician plan to start/restart antiplatelet therapy during trial period
- Abbreviated Injury Scale other than head >3
- Pregnancy
- Inability to understand need for adherence to study protocol
Show all 14Show fewer
- Renal function below DOAC label exclusions
- Any active pathological bleeding (e.g. no acute blood on most recent CT)
- Hypersensitivity to drug or other label contraindication
- Any bleeding that the investigator deems unsafe to restart DOAC at 1 week post injury, or conversely unsafe to hold DOAC to 4 weeks
- Completion of DOAC therapy expected prior to 60 day primary endpoint, e.g. 3-6 month VTE treatment
- Concomitant need for strong inducers/inhibitors of p-gp and CYP3A4
- Low body weight (<45kg)
- Inability to swallow
Trial locations and contacts
No sites are listed yet.
Steven Warach, MD PhD contact
About this study
Official title: A Pilot Trial of Restarting Direct Oral Anticoagulants After Traumatic Intracranial Hemorrhage
Randomized pilot trial of restarting DOACs at 1 week versus 4 weeks after traumatic intracranial hemorrhage
Read the detailed description
Restart TICrH two-center pilot trial will assign patients with anticoagulant-associated traumatic intracranial hemorrhage to restart anticoagulation at 1 week or 4 weeks. Entry into the trial is primarily driven pragmatically by clinician intent to restart any Direct Oral Anticoagulant (DOAC, i.e. apixaban, rivaroxaban, edoxaban, dabigatran. There is no head to head evidence of superiority of any drug) after anticoagulant-associated traumatic intracranial hemorrhage and equipoise concerning restart of anticoagulation at the specified time intervals. DOAC will be at label dose with label adjustments for creatinine clearance. DOAC will be at continuation dose, i.e. not initial therapy high doses in the setting of VTE.
- Conditions
- Anticoagulants; Increased
- Being tested
- Apixaban
- Keywords
- restart, anticoagulant, DOAC
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApixabanDrug
Also called Rivaroxaban, Edoxaban, Dabigatran
Direct Oral Anticoagulation all at label dose and frequency
| Study group | Role | What they receive |
|---|---|---|
| 1 week restart | Active comparator | restart DOAC at 1 week post injury at label dose and frequency Receives: Drug: Apixaban |
| 4 week restart | Active comparator | restart DOAC at 4 weeks post injury at label dose and frequency Receives: Drug: Apixaban |
What is being measured
The primary outcome is the main question the study is designed to answer.
60-day composite endpoint
A 60-day composite endpoint that includes the following clinical events: New or expansion of intracranial hemorrhage, other BARC3a or above major hemorrhage 28, stroke, systemic embolism, myocardial infarction, proximal lower extremity deep vein thrombosis, pulmonary embolism and cardiovascular death
Measured: 60 days
Secondary outcomes (3)
Disability Rating Scale (0-29 scale range)
Functional Measure
Measured: 60 days
Modified Rankin Scale (0-6 scale range)
Functional Measure
Measured: 60 day
Standard Gamble
The standard gamble is the gold standard for analysis of decision making under uncertainty 7. It is an interview technique that begins with a description of a disease state. The patient is then asked to imagine suffering the disease and having a choice between taking a medication that might cure them but also might kill them. The so-called ping-pong method requires the interviewer to start with a hypothetical scenario of 0% probability of cure and 100% probability of a painless instant death. The interviewer then asks the patient if they would take the medication. He then flips the scenario, 100% cure, 0% death. He then goes back and forth between successive scenarios of lower death higher cure and lower cure higher death. Eventually, the patient settles at an equipoise and indecision of whether the risk of dying is worth incurring to take the medication and cure the disease. This is the patient's utility for that disease, expressed as a number between 0 and 1.
Measured: pre-randomization (The day before randomization, which must occur within 6 days of index injury) and after endpoints (the day after one of the endpoints occurs. We cannot know precisely when this will occur in the 60 day follow up period)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2021
- Study start1 Jul 2021 (estimated)
- Primary completion1 Jul 2023 (estimated)
- Study completion1 Jul 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Anticoagulants; IncreasedStudies of the same condition, open and under way.
- More trials run by University of Texas at AustinThe 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized trial of 1 versus 4 week DOAC restart after TICrH
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Texas at Austin
- Sponsor type
- University, hospital or other
- Collaborators
- University of Kansas
- Responsible party
- Principal investigator, Truman J Milling Jr, University of Texas at Austin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04891861
- Sponsor's protocol ID
- ML42205
- Status last verified
- May 2021
- First submitted
- 10 May 2021
- Last updated
- 19 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Sharing via BIOLINCC
Publications
Milling TJ Jr, Warach S, Johnston SC, Gajewski B, Costantini T, Price M, Wick J, Roward S, Mudaranthakam D, Dula AN, King B, Muddiman A, Lip GYH. Restart TICrH: An Adaptive Randomized Trial of Time Intervals to Restart Direct Oral Anticoagulants after Traumatic Intracranial Hemorrhage. J Neurotrauma. 2021 Jun 1;38(13):1791-1798. doi: 10.1089/neu.2020.7535. Epub 2021 Apr 6.
PubMed 33470152
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Trial of Restarting Direct Oral Anticoagulants After Traumatic Intracranial Hemorrhage
- ClinicalTrials.gov ID
- NCT04891861
- Acronym / sponsor ID
- ML42205
- Conditions
- Anticoagulants; Increased
- Keywords
- restart, anticoagulant, DOAC
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of Texas at AustinUniversity, hospital or other
- Collaborators
- University of Kansas
- Study start
- 1 Jul 2021 (estimated)
- Primary completion
- 1 Jul 2023 (estimated)
- Study completion
- 1 Jul 2023 (estimated)
- First posted
- 19 May 2021 (actual)
- 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.
Randomized pilot trial of restarting DOACs at 1 week versus 4 weeks after traumatic intracranial hemorrhage
Detailed description
Restart TICrH two-center pilot trial will assign patients with anticoagulant-associated traumatic intracranial hemorrhage to restart anticoagulation at 1 week or 4 weeks. Entry into the trial is primarily driven pragmatically by clinician intent to restart any Direct Oral Anticoagulant (DOAC, i.e. apixaban, rivaroxaban, edoxaban, dabigatran. There is no head to head evidence of superiority of any drug) after anticoagulant-associated traumatic intracranial hemorrhage and equipoise concerning restart of anticoagulation at the specified time intervals. DOAC will be at label dose with label adjustments for creatinine clearance. DOAC will be at continuation dose, i.e. not initial therapy high doses in the setting of VTE.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized trial of 1 versus 4 week DOAC restart after TICrH
| Arm | Type | Receives |
|---|---|---|
| 1 week restart | Active comparator | Drug: Apixabanrestart DOAC at 1 week post injury at label dose and frequency |
| 4 week restart | Active comparator | Drug: Apixabanrestart DOAC at 4 weeks post injury at label dose and frequency |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Acute traumatic intracranial hemorrhage on anticoagulation for Atrial Fibrillation (AF) or Venous Thromboembolism (VTE)
- Patient is higher risk for stroke or other thrombotic events as witnessed by having a CHA2DS2-VASc score of > 3 (at least 3 of the following risk factors: age greater than 65, (age > 75 counts for 2 points), history of stroke or TIA (2 points), history of heart failure, history of diabetes, history of atherosclerotic vascular disease, female biological sex, history of hypertension)
- DOAC prescribed at label dose with creatinine clearance adjustments. DOAC at continuation dose, i.e., not initial therapy high doses in the setting of VTE
Key exclusion criteria (14 listed)
- Mechanical Valve or Ventricular Assist Device (VAD)
- SDH >8 mm maximum width or any midline shift at any time point or more than one SDH
- Physician plan to start/restart antiplatelet therapy during trial period
- Abbreviated Injury Scale other than head >3
- 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 |
|---|---|---|
| ApixabanAlso: Rivaroxaban, Edoxaban, DabigatranDirect Oral Anticoagulation all at label dose and frequency | Drug | 1 week restart, 4 week restart |
Primary outcome
60-day composite endpoint
Time frame: 60 days
A 60-day composite endpoint that includes the following clinical events: New or expansion of intracranial hemorrhage, other BARC3a or above major hemorrhage 28, stroke, systemic embolism, myocardial infarction, proximal lower extremity deep vein thrombosis, pulmonary embolism and cardiovascular death
3 secondary outcomes
Disability Rating Scale (0-29 scale range)
Time frame: 60 days
Modified Rankin Scale (0-6 scale range)
Time frame: 60 day
Standard Gamble
Time frame: pre-randomization (The day before randomization, which must occur within 6 days of index injury) and after endpoints (the day after one of the endpoints occurs. We cannot know precisely when this will occur in the 60 day follow up period)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2021.
- Results publication: PubMed 33470152Milling TJ Jr, Warach S, Johnston SC, Gajewski B, Costantini T, Price M, Wick J, Roward S, Mudaranthakam D, Dula AN, King B, Muddiman A, Lip GYH. Restart TICrH: An Adaptive Randomized Trial of Time Intervals to Restart Direct Oral Anticoagulants after Traumatic Intracranial Hemorrhage. J Neurotrauma. 2021 Jun 1;38(13):1791-1798. doi: 10.1089/neu.2020.7535. Epub 2021 Apr 6.
- Individual participant dataSharing planned: Yes. Sharing via BIOLINCC
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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.
Steven Warach, MD PhD contact
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Apixaban in people with Anticoagulants; Increased, run by University of Texas at Austin.
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 14 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: status not confirmed, as of the sponsor's last update on 19 May 2021. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Truman J Milling, MD (5124969742, tmilling@ascension.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
60-day composite endpoint (time frame: 60 days). 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 NCT04891861, which also lists 1 linked publication.
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 19 May 2021.