Desmopressin for treatment of stroke patients on antiplatelet therapy
| ISRCTN | ISRCTN67038373 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN67038373 |
| EudraCT/CTIS number | 2018-001904-12 |
| IRAS number | 233744 |
| ClinicalTrials.gov number | NCT03696121 |
| Secondary identifying numbers | CPMS 38963, IRAS 233744 |
- Submission date
- 08/10/2018
- Registration date
- 22/10/2018
- Last edited
- 22/06/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
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 18 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?
University of Nottingham (UK)
When is the study starting and how long is it expected to run for?
October 2018 to June 2022
Who is funding the study?
National Institute for Health Research (NIHR) (UK)
Who is the main contact?
Diane Havard
diane.havard@nottingham.ac.uk
Contact information
Scientific
Stroke Trials Unit
Mental Health & Clinical Neurosciences
University of Nottingham
D Floor, South Block, Room 2151
Queens Medical Centre
Nottingham
NG7 2UH
United Kingdom
 ORCID ID |
0000-0002-3257-1137 |
|---|---|
| Phone | +44 (0)115 8231775 |
| diane.havard@nottingham.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment, Drug |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant 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 |
| Scientific title | Desmopressin for reversal of Antiplatelet drugs in Stroke due to Haemorrhage (DASH) |
| Study acronym | DASH |
| Study hypothesis | Current study hypothesis as of 12/02/2020: To assess the feasibility of screening, checking the eligibility, approaching, randomizing, administering the intervention and completing follow up for patients treated with desmopressin or placebo to inform a definitive trial Previous 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(s) | Nottingham 2 Research Ethics Committee, 22/08/2018, ref: 18/EM/0184 |
| Condition | Haemorrhagic stroke |
| Intervention | Patients will be randomly allocated to receive either: Intravenous desmopressin: 20 μg in 50 ml Sodium Chloride 0.9% infused over 20 min 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/06/2018 |
| Overall study end date | 30/06/2022 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 50; UK Sample Size: 50 |
| Total final enrolment | 54 |
| Participant inclusion criteria | Current participant inclusion criteria as of 12/02/2020: 1. Aged >18 years 2. Confirmed intracerebral hemorrhage on imaging 3. Less than 24 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) Previous 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 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 | 31/03/2022 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
Study participating centres
Queens Medical Centre
Derby Road
Nottingham
NG7 2UH
United Kingdom
2 Day Road
Aberdeen
AB15 6RE
United Kingdom
London
NW1 2PG
United Kingdom
2-4 Waterloo Place
Edinburgh
EH1 3EG
United Kingdom
Barrack Road
Exeter
EX2 5DW
United Kingdom
Infirmary Square
Leicester
LE1 5WW
United Kingdom
Stoke on Trent
ST4 6QG
United Kingdom
Uttoxeter Road
Derby
DE22 3NE
United Kingdom
Queen Victoria Road
Newcastle upon Tyne
NE1 4LP
United Kingdom
Blackshaw Road
Tooting
London
SW17 0QT
United Kingdom
Sponsor information
University/education
Research and Innovation
East Atrium Jubilee Conference Centre
Triumph Road
Nottingham
NG8 1DH
England
United Kingdom
| Phone | +44 (0)115 8467906 |
|---|---|
| bb-sponsor@nottingham.ac.uk | |
"ROR" |
https://ror.org/01ee9ar58 |
Funders
Funder type
Government
No information available
Results and Publications
| Intention to publish date | 31/03/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| 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 plan | The datasets generated during and/or analysed during the current study will be available upon request from Professor Nikola Sprigg (nikola.sprigg@nottingham.ac.uk). |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | Peer reviewed protocol article | 10/11/2020 | 11/08/2022 | Yes | No |
| Results article | 01/07/2023 | 22/06/2023 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
22/06/2023: Publication reference added.
17/03/2023: Total final enrolment added.
11/08/2022: Protocol file uploaded.
23/03/2022: The following changes have been made:
1. The overall trial end date has been changed from 30/09/2022 to 30/06/2022 and the plain English summary has been updated to reflect this change.
2. The study contact address has been updated.
3. The address of the trial participating centre "The Newcastle Upon Tyne Hospitals NHS Foundation Trust" has been updated.
4. The individual participant data (IPD) sharing statement has been added.
5. The IRAS number has been added.
21/02/2022: The following changes have been made:
1. The recruitment end date has been changed from 30/09/2021 to 31/03/2022.
2. Recruitment has resumed.
17/02/2022: The following changes have been made:
1. The overall trial end date has been changed from 31/12/2021 to 30/09/2022 and the plain English summary updated accordingly.
2. The intention to publish date has been changed from 31/12/2021 to 31/03/2023.
30/06/2021: The following changes have been made:
1. The recruitment end date has been changed from 31/03/2020 to 30/09/2021.
2. The overall trial end date has been changed from 31/12/2020 to 31/12/2021 and the plain English summary has been updated to reflect this change.
3. The intention to publish date has been changed from 30/12/2020 to 31/12/2021.
4. The trial contact has been updated.
07/04/2020: Due to current public health guidance, recruitment for this study has been paused.
12/02/2020: The following changes have been made:
1. The overall trial end date has been changed from 30/04/2020 to 31/12/2020.
2. The recruitment end date has been changed from 30/11/2019 to 31/03/2020.
3. The intention to publish date has been changed from 31/04/2020 to 30/12/2020.
4. The trial website has been added.
5. The study hypothesis has been updated.
6. The participant inclusion criteria have been updated.
7. The plain English summary has been updated to reflect the changes above.
23/05/2019: ClinicalTrials.gov number added.
25/03/2019: The condition has been changed from "Specialty: Stroke, Primary sub-specialty: Acute Care; Health Category: Stroke; Disease/Condition: Cerebrovascular diseases" to "Haemorrhagic stroke" following a request from the NIHR.
