Desmopressin for Reversal of Antiplatelet Drugs in Stroke Due to Haemorrhage

Stroke, Acute Clinical Trial

— DASH  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03696121
• Other study ID #: 18040
• Status: Completed
• Phase: Phase 2
• Start date: April 1, 2019
• Est. completion date: June 30, 2022

Study information

• Verified date: November 2022
• Source: University of Nottingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: June 30, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 110 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hemorrhage
• Stroke
• Stroke, Acute

Intervention

Drug:
• Desmopressin Injection
Single dose 20 micrograms in 50ml Normal Saline as intravenous injection infused over 20 minutes
• Normal saline
Single dose 50ml Normal Saline as intravenous injection infused over 20 minutes

Locations

Country	Name	City	State
United Kingdom	Nottingham City Hospital	Nottingham	Notts

Sponsors (2)

Lead Sponsor	Collaborator
University of Nottingham	National Institute for Health Research, United Kingdom

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of eligible patients who received allocated treatment	Number - higher number indicates feasibility of trial	90 days
Primary	Rate of eligible patients randomised	Shorter period of time to recruit number of patients indicates trial is feasibility;e	18 months
Primary	Proportion of eligible patients and randomised	Are there sufficient numbers of patients to justify a larger trial	18 months
Primary	Proportion of participants followed up at 90 days	Higher number indicates feasibility	90 days
Primary	Proportion of patients with full outcome data available, and reasons for non-availability	Higher number indicates feasibility	90 days
Primary	Proportion of eligible patients approached	Higher number indicates feasibility	18 months
Primary	Adherence to intervention	Higher number indicates feasibility	18 months
Secondary	Death or dependency at 90 days	Lower number indicates positive outcome	18 months
Secondary	Number of patients dead or suffered serious adverse events	Number - higher number indicates worse outcome	Day 28 and 90
Secondary	Change in intracerebral haemorrhage volume at 24 hours	Higher volume indicates worse outcome	24 hours
Secondary	Disability - Barthel index	Scores range from 0 - 100, with lower scores indicating increased disability.	Day 90
Secondary	Quality of life - EuroQol	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).	Day 90
Secondary	Cognition - telephone MMSE	Scores are out of 22, with lower scores indicating cognitive impairment	Day 90
Secondary	Length of hospital stay	Number of days - higher number indicates longer length of stay	Day 90
Secondary	Discharge destination	Destination of participant following discharge from hospital	18 months
Secondary	Health Economic assessment (EQ5D)	Range 0-100, Higher score indicates better health	90 Days
Secondary	Serious adverse events (including thromboembolic events)	Higher volume indicates worse outcome	Day 90
Secondary	Change in factor vIII, Von Willebrand Factor antigen and Von Willebrand Factor activity will be assessed		One hour post administration of Desmopressin