Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT06322953 |
| Other study ID # |
RG442-21 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
July 1, 2024 |
| Est. completion date |
July 31, 2028 |
Study information
| Verified date |
March 2024 |
| Source |
Walton Centre NHS Foundation Trust |
| Contact |
Laura Wright |
| Phone |
+44(0)151 795 8751 |
| Email |
restart.trial[@]liverpool.ac.uk |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Older people falling from a standing height is the most common cause of hospital admission
for head injury. Up to 1 in 3 patients admitted are taking a tablet medication which thins
the blood, known as an oral anticoagulant. This type of medication can increase the
likelihood of bleeding in the brain. Many patients are taking oral anticoagulation due to
having an irregular heartbeat (called atrial fibrillation) or because of having a previous
stroke or blood clots. When a scan shows blood in the brain, oral anticoagulation is nearly
always stopped. However, this leaves the question of when it is safe to restart them. The
risk of making the bleeding in the brain worse must be balanced against the risk of having a
stroke or blood clots. There is no clear evidence on the safest time to restart oral
anticoagulation, but most neurosurgeons advise restarting them 1-4 weeks after head injury.
The number of people who have a bleed on their brain after a head injury is increasing and
further brain bleeding or a stroke can have a serious effect on patients' lives and their
on-going healthcare needs. Public and patient groups have highlighted that many patients want
to stop taking oral anticoagulation after a bleed but they may be unaware of the vital
importance of restarting this medication to prevent strokes and blood clots. The most popular
oral anticoagulation prescribed has changed in recent years from warfarin to newer
medications called Direct Oral Anti-Coagulants (DOACs).
This trial will recruit 1084 people who are admitted to hospital with a bleed on the brain
caused by a head injury who were taking oral anticoagulation before their head injury and
have been prescribed a Direct Oral Anti-Coagulant (DOAC) for previously diagnosed medical
condition. Patients on other Oral Anti-Coagulants, such as Warfarin may also be able to take
part. The main purpose of the trial is to determine when is most beneficial time for people
to start or restart a DOAC after their head injury. People will be asked to start the
medication either 1 week or 4 weeks after their head injury. They will be then followed
closely for 12 weeks and any major bleeding events or a blood clots (thrombotic events) such
as a stroke or heart attack will be recorded. The study will also look at the person's
overall quality of life, how they recover physically, the number of people who die, the costs
of the treatment, and the attitudes of people and their caregivers to starting or restarting
a DOAC.
Description:
Head injury in older patients is becoming increasingly common. The 2017 England and Wales
trauma network review reports an older person falling from standing height as the commonest
type of major trauma, and most frequently results in injury to the head. By 2050, 1 in 6
people will be aged over 65, and with approximately 30% of older adults falling each year,
the incidence of head injury will rise. In conjunction, there is a high prevalence of oral
anticoagulant (OAC) use in this older population, driven by increased incidence of atrial
fibrillation (AF), the commonest heart rhythm disorder, which is related to aging. It
increases the risk of stroke 5-fold and should be considered for treatment with oral
anticoagulants OACs depending on risk factor assessment by the CHA2DS2VASc (C - Congestive
heart failure (1 point) H - Hypertension (1 point) A2 - Age ≥75 years (2 points) D - Diabetes
mellitus (1 point) S2 - Prior Stroke or transient ischemic attack (2 points) V - Vascular
disease (e.g., peripheral artery disease, myocardial infarction, aortic plaque) (1 point) A -
Age 65-74 years (1 point) Sc - Female sex category (1 point) score). OAC prescribing for such
patients has more than doubled in the United Kingdom (UK) since 20008 and between 20-35% of
older patients admitted with head injury causing intracranial haemorrhage (tICrH), are taking
an OAC at the time of injury. Standard care dictates that OACs should be stopped in the
majority of cases to reduce the risk of progressive or new ICrH. Despite a low risk of new or
on-going Intracranial Hemorrhage (ICrH) 48 hours after injury, there is a reluctance from
clinicians to restart OACs for fear of evoking re-bleeding. This must be balanced against the
increased risk of thromboembolism in patients not taking their OAC, predisposing AF patients
to increased risk of stroke, systemic thromboembolism and all-cause mortality. Currently
there is no clear consensus on the optimal practice on the timing for restarting OACs post-
traumatic intracranial hemorrhage (tICrH). OAC medications are traditionally divided into
vitamin K antagonists (e.g., warfarin) and Direct Oral Anticoagulants (DOACs). DOAC
prescribing has increased substantially over the last decade. Benefits include an immediate
therapeutic effect, fixed dosing, fewer drug interactions and no monitoring when compared to
warfarin. Previous meta-analyses and trials demonstrate that DOACs are at least as effective
as warfarin in the prevention of stroke in AF patients, and have a lower rate of associated
ICrH and mortality. DOACs (eg Apixaban, dabigatran, edoxaban and rivaroxaban) are recommended
by The National Institute for Health and Care Excellence (NICE) for those over 65 with AF and
a CHA2DS2VASc score of 2 or above and considered for men with AF and a CHA2DS2VASc score of
16. For those already taking a Vitamin K antagonist (VKA) (e.g., Warfarin) NICE recommends
that the option of switching to a DOAC should be discussed. This study will focus on patients
who are taking a DOAC or Vitamin K antagonist for AF or venous thromboembolism (VTE) at the
time of tICrH which is stopped due to risk of further bleeding. Patients will then either be
restarted on their DOAC, or the option of switching to a DOAC from their current Vitamin K
antagonist will be discussed, as these have a superior safety profile (significantly reduced
risk of haemorrhagic stroke and intracerebral haemorrhage compared to warfarin) and reflects
best practice following tICrH.
Studies suggest evidence of early tICrH expansion (within 48hrs) on routine repeat imaging
occurs in 10-37% of patients on OAC, indicating the need to stop OAC. This risk reduces
substantially over time. A recent trial assessing patients with a major bleed on OACs,
reported re-bleeding rates of 4.3% within 30 days, when excluding the first 3 days from the
initial bleed. The bleeding rate was only 4.5% in those who restarted their OAC within 2
weeks, with a net benefit (Hazard ratio 0.384 combining thrombosis, bleeding and death rate)
when compared to those that did not restart OAC within 2 weeks. Another study focusing on
tICrH reported a 5% readmission rate for re-bleeding within 30-days in patients who did not
restart their DOAC. There is a paucity of high-level data on delayed (>72hrs) haemorrhage
rates after tICrH and withholding OACs results in an elevated risk of thrombotic events such
as stroke, myocardial infarction (MI) and VTE. A trial of 352 patients suffering a major
bleed whilst on a DOAC demonstrated that thrombotic events increase from around 4% at 1 week
to 10% at 4 weeks. At 3 months, patients who have restarted OAC have fewer strokes [Hazard
Ratio (HR) 0.85, 95% confidence intervals (CI) 0.43-1.68] and deaths [HR 0.5, 95% CI
0.35-0.72], despite increased bleeding [HR 1.62, 95% CI 0.95-2.75] compared to those who have
not restarted OAC.
