Desmopressin for Reversal of Antiplatelet Drugs in Stroke Due to Haemorrhage (DASH)

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.

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.

Consists of two parts: a descriptive system (Part I) and a visual analogue scale (VAS) (Part II). Part 1 consists of 5 single-item dimensions. Scores range from 5 - 15 with lower scores indicating no problems to higher scores indicating extreme problems. Part II uses a vertical graduated VAS (thermometer) to measure health status, ranging from worst imaginable health state (0) to best imaginable health state (100).

Change in factor vIII, Von Willebrand Factor antigen and Von Willebrand Factor activity will be assessed

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.

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.