Clinical trial NCT03696121: Desmopressin for Reversal of Antiplatelet Drugs in Stroke Due to Haemorrhage
Official title: Desmopressin for Reversal of Antiplatelet Drugs in Stroke Due to Haemorrhage (DASH)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stroke, Acute
Keywords: intracerebral haemorrhage
Lead sponsor: University of Nottingham
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
First posted: 2018-10-04
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 110
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Haemorrhagic stroke, an emergency caused by bleeding in the brain, often leads to death or long-term disability. A quarter of these patients are taking blood-thinning drugs (antiplatelet drugs, such as aspirin) because they are at risk of a heart attack or ischaemic stroke. Patients taking these drugs are more likely to die or be disabled if they have a haemorrhagic stroke. At present, there is no effective treatment for reversing their effects. Desmopressin is a drug which may reverse the effects of antiplatelet drugs and stop bleeding. The investigators would like to run a large randomised trial to see if Desmopressin can reduce the number of people who die or are disabled after haemorrhagic stroke.

Detailed description: Intracerebral haemorrhage is a medical emergency, caused by a blood vessel bleeding directly into the brain. Outcome is directly related to the amount of bleeding that occurs. Many patients die early and others are left with significant disability. A quarter of all people with intracerebral haemorrhage are taking an antiplatelet drug, which is associated with larger volumes of brain haemorrhage and significantly worse outcomes. Four to five million people are taking antiplatelet drugs in the UK and use continues to rise in an ageing population.

Despite advances in treatment of ischaemic stroke, there is no effective drug treatment for intracerebral haemorrhage. Treatment for intracerebral haemorrhage has been identified as a priority area by Stroke Association and stroke survivors.

Desmopressin is a drug that reverses blood thinning effects of antiplatelet drugs, by indirectly increasing platelet adhesion, which the investigators hypothesise will minimise the devastating consequences of intracerebral haemorrhage associated with antiplatelet drugs. Desmopressin is commonly used in patients with inherited platelet dysfunction disorders and is an appealing treatment for antiplatelet-associated intracerebral haemorrhage. A recent systematic review did not find any randomised controlled trials evaluating desmopressin for antiplatelet-associated intracerebral haemorrhage. Desmopressin is affordable, available and could be implemented clinically across the UK and worldwide in the next five years with immediate benefit for stroke patients, their families and society.

Eligibility criteria: Inclusion Criteria:

* Adults (≥18 years)
* Confirmed intracerebral haemorrhage on imaging
* Less than 24 hours from onset of symptoms \[or from when last seen free of stroke symptoms\]
* Prescribed and thought to be taking a daily oral antiplatelet drug in the preceding seven days (cyclooxygenase inhibitors, phosphodiesterase inhibitors or P2Y12 inhibitors)
* Signed consent (or waiver of consent).

Exclusion Criteria:

* Aneurysmal subarachnoid haemorrhage known at time of enrolment
* Haemorrhage suspected to be due to transformation of ischaemic stroke
* Haemorrhage known to be due to thrombolytic drug
* Haemorrhage known to be due to venous thrombosis
* Risk/s of fluid retention associated with desmopressin judged clinically significant by the attending physician (for example patients with pulmonary oedema and/or cardiac failure) - - Significant hypotension (systolic blood pressure \<90mmHg)
* Known drug-eluting coronary artery stent in previous three months
* Allergy to desmopressin
* Pregnant or breast-feeding
* Life expectancy less than four hours, or planned for palliative care only
* Glasgow coma scale less than 5, mRS \>4.

Primary outcomes:
measure: Number of eligible patients who received allocated treatment
timeFrame: 90 days
measure: Rate of eligible patients randomised
timeFrame: 18 months
measure: Proportion of eligible patients and randomised
timeFrame: 18 months
measure: Proportion of participants followed up at 90 days
timeFrame: 90 days
measure: Proportion of patients with full outcome data available, and reasons for non-availability
timeFrame: 90 days
measure: Proportion of eligible patients approached
timeFrame: 18 months
measure: Adherence to intervention
timeFrame: 18 months
Secondary outcomes:
measure: Death or dependency at 90 days
timeFrame: 18 months
measure: Number of patients dead or suffered serious adverse events
timeFrame: Day 28 and 90
measure: Change in intracerebral haemorrhage volume at 24 hours
timeFrame: 24 hours
measure: Disability - Barthel index
timeFrame: Day 90
measure: Quality of life - EuroQol
timeFrame: Day 90
measure: Cognition - telephone MMSE
timeFrame: Day 90
measure: Length of hospital stay
timeFrame: Day 90
measure: Discharge destination
timeFrame: 18 months
measure: Health Economic assessment (EQ5D)
timeFrame: 90 Days
measure: Serious adverse events (including thromboembolic events)
timeFrame: Day 90
measure: Change in factor vIII, Von Willebrand Factor antigen and Von Willebrand Factor activity will be assessed
timeFrame: One hour post administration of Desmopressin
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
state: Notts
Study officials:
affiliation: University of Nottingham
name: Nikola Sprigg
role: PRINCIPAL_INVESTIGATOR
References:
citation: Desborough MJR, Al-Shahi Salman R, Stanworth SJ, Havard D, Brennan PM, Dineen RA, Coats TJ, Hepburn T, Bath PM, Sprigg N. Desmopressin for reversal of Antiplatelet drugs in Stroke due to Haemorrhage (DASH): protocol for a phase II double-blind randomised controlled feasibility trial. BMJ Open. 2020 Nov 10;10(11):e037555. doi: 10.1136/bmjopen-2020-037555.