Condition category
Circulatory System
Date applied
08/10/2018
Date assigned
22/10/2018
Last edited
22/10/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
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 aim of this study is to assess whether it is feasible to run a large trial to see if desmopressin can reduce the number of people who die or are disabled after haemorrhagic stroke.

Who can participate?
Patients aged over 17 with an intracerebral haemorrhage who are taking a daily oral antiplatelet drug

What does the study involve?
Participants are randomly allocated to be treated with either desmopressin or a dummy drug given as a drip via a cannula (needle inserted into a vein, usually into the back of the hand) over about 20 minutes. The treatment is given once, then the treatment stops. Three blood samples are taken from a vein in the arm: one before the treatment to assess blood clotting, one immediately after and another 24 hours after treatment to check salt levels in the blood stream. Wherever possible these are taken with routine blood samples. During the next 7 days, a nurse checks the participant looking in particular for signs of side effects of the treatment. A brain scan is also repeated the day after the treatment to assess the effects of the treatment. The researchers contact the participant’s GP or check with the NHS Information Centre to check on their condition three months after their stroke and to confirm their contact details. Participants are then contacted for a telephone consultation with a member of the research team to check their condition at that time. It involves asking how they are able to move around, about how they feel their life has been affected by the stroke and some brief memory tests. Other than described here, treatment is exactly the same as for all stroke patients.

What are the possible benefits and risks of participating?
Participation in this study may reduce the symptoms of haemorrhagic stroke or improve long-term recovery. However, this cannot be promised, and participation is voluntary. The information obtained may benefit other people who have a stroke in the future. Treatment with any drugs can result in possible side effects and the side effects from desmopressin are generally mild. They can include headache, abdominal pain, low blood pressure and dizziness. The drug can increase the risk of seizures but this is very rare. However, because the treatment works by stopping bleeding there is a chance it can cause an increase in blood clot formation. This can occur in the legs (deep vein thrombosis, DVT) or the lungs (pulmonary embolism, PE) and is potentially very serious and maybe even life threatening. Participants who have previously suffered from blood clots in the legs or lungs may not be able to participate in this study. In 65 previous studies where desmopressin has been used to reduce bleeding during operations, desmopressin was safe. There was no increase in serious side effects, such as blood clots, in the patients who were treated with desmopressin. Because desmopressin is already routinely used in a number of bleeding conditions, the potential benefit of the drug (stopping bleeding in to the brain) is expected to outweigh the low risk of serious side effects (such as blood clots). However, this is not known for certain and all participants will be monitored closely for side effects. Participants must inform their doctor or member of the research team if they feel they have had a reaction to the medication. The blood samples can cause mild discomfort/pain and slight bruising. The extra CT brain scan performed as part of this trial takes less than 5 minutes and does not involve any injections. The scan uses x-rays, which in large amounts can be harmful, but for this extra CT head scan the additional risk from the scan has been judged to be extremely small and is comparable with the annual risk of dying from an accident in the home.

Where is the study run from?
1. Nottingham University Hospitals NHS Trust
2. NHS Grampian
3. University College London Hospitals NHS Foundation Trust
4. NHS Lothian
5. Royal Devon & Exeter NHS Foundation Trust
6. University Hospitals of Leicester NHS Trust
7. University Hospitals of North Midlands NHS Trust
8. Derby Teaching Hospitals NHS Foundation Trust
9. The Newcastle Upon Tyne Hospitals NHS Foundation Trust
10. St Georges University Hospitals NHS Foundation Trust

When is the study starting and how long is it expected to run for?
October 2018 to April 2020

Who is funding the study?
National Institute for Health Research (NIHR) (UK)

Who is the main contact?
1. Robert Gray
robert.gray@nottingham.ac.uk
2. Diane Havard
diane.havard@nottingham.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Mr Robert Gray

ORCID ID

Contact details

A07 Clinical Sciences Building
City Hospital Campus
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
+44 (0)115 823 0287
Robert.gray@nottingham.ac.uk

Type

Scientific

Additional contact

Mrs Diane Havard

ORCID ID

http://orcid.org/0000-0002-3257-1137

Contact details

A07 Clinical Sciences Building
City Hospital Campus
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
+44 (0)115 8231775
diane.havard@nottingham.ac.uk

Additional identifiers

EudraCT number

2018-001904-12

ClinicalTrials.gov number

Protocol/serial number

38963

Study information

Scientific title

Desmopressin for reversal of Antiplatelet drugs in Stroke due to Haemorrhage (DASH)

Acronym

DASH

Study hypothesis

To assess the feasibility of a large randomised trial to see if Desmopressin can reduce the number of people who die or are disabled after haemorrhagic stroke.

Ethics approval

Nottingham 2 Research Ethics Committee, 22/08/2018, ref: 18/EM/0184

Study design

Randomised; Interventional; Design type: Treatment, Drug

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Participant information sheet (MS Word download): http://dash-1.ac.uk/links/ptinf; Nominee information sheet (MS Word download): http://dash-1.ac.uk/links/relinf; Short pictorial information sheet (MS Word download): http://dash-1.ac.uk/links/picinf

Condition

Specialty: Stroke, Primary sub-specialty: Acute Care; Health Category: Stroke; Disease/Condition: Cerebrovascular diseases

Intervention

Patients will be randomly allocated to receive either:
Intravenous desmopressin: 20μg in 50 ml Sodium Chloride 0.9% infused over 20 minutes
Comparator: placebo (Sodium Chloride 0.9% intravenous infusion) administered by identical regimen

The participant's involvement in the trial will last for 90 days, from randomisation (day 1) until final follow-up at 90 days.

Baseline (Day 1): CT scan to confirm the diagnosis of haemorrhagic stroke, clinical assessment, blood sample to assess baseline clotting function (P-selectin), blood sample to look for changes in clotting function one hour after administration of desmopressin, blood pressure measurement after treatment is complete.

End of treatment (24 hours after treatment - day 2):Clinical assessment, blood sample to assess serum sodium, CT brain scan to assess bleeding and to look for any increased bleeding.

Day of discharge/death: document discharge destination(e.g. home/hospital/rehabilitation unit) and length of hospital stay.

Day 90 – telephone interview: completion of questionnaires - Disability (Barthel index, Quality of life (EuroQol) and Cognition (telephone MMSE)

Intervention type

Drug

Phase

Phase II

Drug names

Desmopressin

Primary outcome measure

The feasibility of randomising, administering the intervention, and completing follow-up for patients treated with desmopressin or placebo to inform a definitive trial; Timepoint(s): End of the study; assessed using:
1. Number of eligible patients who receive allocated treatment
2. Rate of eligible patients randomised
3. Proportion of eligible patients approached
4. Proportion of eligible patients randomised and reasons for non-randomisation
5. Adherence to intervention
6. Proportion of participants followed up to 90 days and reasons for loss to follow up
7. Proportion of randomised participants with full outcome data available, and reasons for non-availability

Secondary outcome measures

1. Hyponatraemia, measured using U&E blood test (Sodium Na level) at 24 hours
2. Early case fatality <28 days, measured using SAE recording/death/discharge CRF
3. Case fatality at day 90, measured using alive and well check GP
4. Serious adverse events (including thromboembolic events) up to day 90, measured using SAE reporting CRF
5. Change in intracerebral haemorrhage volume at 24 hours, measured using CT/MRI scan volume measurement
6. Discharge destination, measured using discharge CRF at discharge
7. Disability, measured using the Barthel index at day 90
8. Quality of life, measured using EuroQol at day 90
9. Cognition, measured using telephone MMSE at day 90
10. Length of hospital stay, measured using hospital admission record at discharge
11. Health economic assessment using EQ-5D at day 90 follow up
12. Assessment of baseline platelet dysfunction (P-selectin) and correlation with response to desmopressin, measured using P-selectin blood test at enrollment after consent pre-treatment
13. Change in factor VIII, VWF antigen and VWF activity at one hour after administration of desmopressin, measured using factor VIII, VWF antigen and VWF assays done on blood tests taken before and after treatment

Overall trial start date

01/06/2018

Overall trial end date

30/04/2020

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Adults (>17 years)
2. Confirmed intracerebral haemorrhage on imaging
3. Less than 12 hours from onset of symptoms [or from when last seen healthy]
4. Prescribed and thought to be taking a daily oral antiplatelet drug in the preceding seven days (cyclooxygenase inhibitors, phosphodiesterase inhibitors or P2Y12 inhibitors)
5. Signed consent (patient/personal/professional representative)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 50; UK Sample Size: 50

Participant exclusion criteria

1. Aneurysmal subarachnoid haemorrhage known at time of enrolment
2. Haemorrhage known to be due to transformation of infarction
3. Haemorrhage known to be due to thrombolytic drug
4. Haemorrhage known to be due to venous thrombosis
5. 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)
6. Significant hypotension (systolic blood pressure < 90mmHg)
7. Known drug-eluting coronary artery stent in previous three months
8. Allergy to desmopressin
9. Pregnant or breastfeeding
10. Life expectancy less than four hours, or planned for palliative care only
11. Glasgow coma scale less than 5
12. mRS > 4
13. Participation in another concurrent drug trial

Recruitment start date

01/11/2018

Recruitment end date

30/11/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Nottingham University Hospitals NHS Trust
Trust Headquarters Queens Medical Centre Derby Road
Nottingham
NG7 2UH
United Kingdom

Trial participating centre

NHS Grampian
Summerfield House 2 Day Road
Aberdeen
AB15 6RE
United Kingdom

Trial participating centre

University College London Hospitals NHS Foundation Trust
250 Euston Road
London
NW1 2PG
United Kingdom

Trial participating centre

NHS Lothian
Waverley Gate 2-4 Waterloo Place
Edinburgh
EH1 3EG
United Kingdom

Trial participating centre

Royal Devon & Exeter NHS Foundation Trust
Royal Devon & Exeter Hospital Barrack Road
Exeter
EX2 5DW
United Kingdom

Trial participating centre

University Hospitals of Leicester NHS Trust
Leicester Royal Infirmary Infirmary Square
Leicester
LE1 5WW
United Kingdom

Trial participating centre

University Hospitals of North Midlands NHS Trust
Newcastle Road
Stoke on Trent
ST4 6QG
United Kingdom

Trial participating centre

Derby Teaching Hospitals NHS Foundation Trust
Royal Derby Hospital Uttoxeter Road
Derby
DE22 3NE
United Kingdom

Trial participating centre

The Newcastle Upon Tyne Hospitals NHS Foundation Trust
Freeman Hospital Freeman Road High Heaton
Newcastle upon Tyne and Wear
NE7 7DN
United Kingdom

Trial participating centre

St Georges University Hospitals NHS Foundation Trust
St Georges Hospital Blackshaw Road Tooting
London
SW17 0QT
United Kingdom

Sponsor information

Organisation

University of Nottingham

Sponsor details

Research and Innovation
East Atrium Jubilee Conference Centre
Triumph Road
Nottingham
NG8 1DH
United Kingdom
+44 (0)115 8467906
bb-sponsor@nottingham.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

NIHR Central Commissioning Facility (CCF); Grant Codes: PB-PG-0816-20011

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Protocol (PDF): http://dash-1.ac.uk/links/protocol

Trial results will be published in a peer reviewed academic journal. Reporting will be in compliance with CONSORT recommendations. The focus of that article will be to discuss the feasibility of using desmopressin to reverse the effects of antiplatelet drugs in haemorrhagic stroke. When the study is complete summary findings will post on the support group website. Findings will also be presented at conferences such as UK Stroke Forum, European Stroke Conference, World Stroke Congress, International Society on Haemostasis and Thrombosis, British Society for Haematology annual meeting, and American Society for Haematology annual meeting.

The trial results will be published by named members of the trial team, on behalf of the DASH Trial Collaborative Group. Members of the collaborative group will be listed in the publication, based on contributorship. Any secondary publication may be published by named individuals, but with appropriate acknowledgement of the collaborative group.

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

30/04/2021

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes