MedPath

Desmopressin for Reversal of Antiplatelet Drugs in Stroke Due to Haemorrhage

Phase 2
Completed
Conditions
Stroke, Acute
Interventions
Drug: Normal saline
Registration Number
NCT03696121
Lead Sponsor
University of Nottingham
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
54
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
InterventionDesmopressin InjectionDesmopressin injection
ControlNormal salineNormal Saline
Primary Outcome Measures
NameTimeMethod
Proportion of eligible patients approached18 months

Higher number indicates feasibility

Number of eligible patients who received allocated treatment90 days

Number - higher number indicates feasibility of trial

Rate of eligible patients randomised18 months

Shorter period of time to recruit number of patients indicates trial is feasibility;e

Adherence to intervention18 months

Higher number indicates feasibility

Proportion of participants followed up at 90 days90 days

Higher number indicates feasibility

Proportion of eligible patients and randomised18 months

Are there sufficient numbers of patients to justify a larger trial

Proportion of patients with full outcome data available, and reasons for non-availability90 days

Higher number indicates feasibility

Secondary Outcome Measures
NameTimeMethod
Discharge destination18 months

Destination of participant following discharge from hospital

Change in intracerebral haemorrhage volume at 24 hours24 hours

Higher volume indicates worse outcome

Death or dependency at 90 days18 months

Lower number indicates positive outcome

Disability - Barthel indexDay 90

Scores range from 0 - 100, with lower scores indicating increased disability.

Quality of life - EuroQolDay 90

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).

Cognition - telephone MMSEDay 90

Scores are out of 22, with lower scores indicating cognitive impairment

Number of patients dead or suffered serious adverse eventsDay 28 and 90

Number - higher number indicates worse outcome

Length of hospital stayDay 90

Number of days - higher number indicates longer length of stay

Health Economic assessment (EQ5D)90 Days

Range 0-100, Higher score indicates better health

Serious adverse events (including thromboembolic events)Day 90

Higher volume indicates worse outcome

Change in factor vIII, Von Willebrand Factor antigen and Von Willebrand Factor activity will be assessedOne hour post administration of Desmopressin

Trial Locations

Locations (1)

Nottingham City Hospital

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Nottingham, Notts, United Kingdom

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