Prevention of Hypertensive Injury to the Brain by Intensive Treatment in IntraCerebral Haemorrhage (PROHIBIT-ICH) (PROHIBIT-ICH)

• ClinicalTrials.gov Identifier: NCT03863665
• Recruitment Status: Recruiting
• First Posted: March 5, 2019
• Last Update Posted: April 17, 2019
• Sponsor: University College, London
• Information provided by (Responsible Party): University College, London

Study Description

Brief Summary:

PROHIBIT-ICH will randomise participants to compare a strategy of intensive BP treatment (target <120/80 mm Hg) guided by telemetric home monitoring, versus standard primary care (current RCP guideline is 130/80 mm Hg), in 112 adult survivors of hypertension-related ICH. The investigators will establish the feasibility and safety of the intervention, the efficacy of BP reduction, and explore whether it reduces the progression of SVD-related injury on brain MRI.

Condition or disease	Intervention/treatment	Phase
Intracerebral Hemorrhage	Device: A&D BP Digital Blood Pressure Monitor (UA-767PBT-Ci) CE Declaration UA-767PBT-Ci	Not Applicable

Detailed Description:

About 112 eligible participants will be identified from primary care by a member of the research practitioner or member of research/clinical teams (patient identification sites) outpatient clinics (stroke clinics, neurology clinics, geriatric clinics, neurosurgical clinics) and from acute stroke units or high dependency units at participating hospitals. Patients may be under the care of stroke physicians, geriatricians, neurologists, or neurosurgeons. The Bluetooth telemetric home monitoring equipment will be provided either at hospital discharge or after hospital discharge and the equipment will be set up in the participant's home. Patients will be handed or sent a participant information leaflet. An opportunity to meet a member of the research team will be arranged in person by a member of the clinical care team or subsequently by phone by a member of the research team. All interested participants will have an opportunity to ask questions about the study and these will be answered by a member of the research team prior to enrolment.

Consent:

Participants will be asked to give written consent prior to participation, after a meeting with a researcher when any questions about the study will be answered.

Baseline:

At baseline, the following trial specific procedures will be carried out after consent as a requirement for the study to commence:

• Medical History recorded
• Blood pressure medication and dose recorded
• Blood pressure (BP)
• Blood test (Venepuncture)
• MRI Scan
• Cognitive functional change Assessment (Montreal Cognitive Assessment)
• Completion of the EQ-5D questionnaire - 24 hour ABPM When a person agrees to participate demographic, contact and medical history information necessary to conduct the study will be recorded. Each participant will be allocated a unique trial number. Relevant sections of medical notes and data collected during the study may be looked at by the researchers from regulatory authorities or from the NHS Trust, where it is relevant to the subject's participation in the trial.

Randomisation:

Patients will be randomized in a 1:1 group assignment ratio to intensive BP lowering (intervention group) or standard care (control group) using an on line randomization service (Sealed Envelope), available 24 hours a day.

Intervention:

The Telemetric Bluetooth home Blood Pressure-monitoring device will monitor participant's BP to keep the target of 120/80mm Hg, if this is not achievable then the BP medication will be adjusted accordingly in order to achieve a target of 120/80mm Hg at 3 months follow-up. BP readings (3 readings over 10-minutes in the seated position in the non dominant arm, unless hemiparesis) will be taken 3 times daily (early morning, early afternoon and evening). All BP data will be automatically transmitted centrally in real time to the device co-ordination site in Oxford. A dedicated research member will be responsible for checking all BP data daily on patients in the study, and will advise on adjusting medication according to a standard protocol based on the latest BHS guideline, to ensure that BP is lowered to the intervention arm target. The local study centre will send new prescriptions directly to patients (with communication simultaneously with the GP). For dose changes, advice will be given to participants by phone by the central study team. All medication changes will be notified to the local research team and GP; responsibility for BP treatment will be by the local PI.

Follow up:

3 month Follow-up (Visit two): Completion of 3 month CRF, blood pressure recorded and completion of Modified Cognitive assessment, EQ-5D questionnaire and home blood pressure acceptability questionnaire. 24-hour ABPM to be performed at the time of the 3 month follow-up visit.

12 month follow-up (Final visit): Completion of 12 month CRF, blood pressure recorded, and completion of Cognitive assessment and EQ-5D questionnaire. 24-hour ABPM to be performed at the time of the 12 month follow-up visit.

An MRI scan will be performed at baseline and the 12 month follow-up visit on all participants to identify markers of cerebral small vessel disease including:

• change in white matter hyperintensity volume
• change in white matter microstructure (DTI)
• change in the number of CMBs
• change in cerebral atrophy

Primary outcomes:

(a) BP study (i) Efficacy: the magnitude of difference in BP at 3 months in the intervention arm versus control arm compared with baseline measures (ii) Feasibility: consent rate; dropout rate from the intervention prior to 1 month; patient approval of the monitoring process (iii) Safety: serious adverse event related to reducing BP in intervention arm (b) Imaging study (i) Efficacy: the progression in MRI white matter hyperintensity (WMH) volume over 1 year

Secondary outcomes:

1. BP study: clinical outcomes including recurrent vascular events and cognition; number of BP lowering drugs at 3 months and at 1 year follow-up visits; mean daytime BP at 1 year on 24-hour ABPM
2. Imaging study: neuroimaging outcomes including (but not limited to) the proportion of patients who develop new cerebral microbleeds (CMBs) over 1 year; number of new CMBs at 1 year; new infarcts or intracerebral haemorrhages at 1 year; change in mean diffusivity (MD), fractional anisotropy (FA) and other 3T DTI metrics; change in cerebral blood flow (CBF) on 3T PCASL; change in total brain volume, white matter volume and grey matter volume on 3T T1 volumetric images; composite neuroimaging measures (e.g summary SVD scores)

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 112 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Patients will be randomised in a 1:1 ratio to intervention or control arms of the study. Participants and their physicians will not be blinded to study arm allocation
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Prevention of Hypertensive Injury to the Brain by Intensive Treatment in IntraCerebral Haemorrhage
• Actual Study Start Date: March 11, 2019
• Estimated Primary Completion Date: December 1, 2021
• Estimated Study Completion Date: December 1, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Telemetric Bluetooth home BP monitors; Telemetric Bluetooth home BP monitors will be provided to participants during their inpatient stay or clinic visit, and will commence 3- times-daily readings immediately. The BP monitoring team will assess BP readings daily and advise medication adjustments to achieve a target BP of <120/80 mm Hg	Device: A&D BP Digital Blood Pressure Monitor (UA-767PBT-Ci) CE Declaration UA-767PBT-Ci; Telemetric home monitoring is a promising strategy to facilitate home BP monitoring after stroke, which should improve adherence and optimize medication to better control BP. Telemetry allows patients with hypertension to monitor their own BP and automatically send the information to a secure website, available to their clinicians to monitor and adjust their treatment.
No Intervention: Standard clinical care; Standard clinical care including usual BP treatment, without home monitoring, undertaken in the clinical care setting

Outcome Measures

Primary Outcome Measures :

1. The efficacy of telemetric BP monitoring to guide intensive BP treatment in ICH survivors by detecting a statistically significant reduction in BP in the intervention compared to the control arm at 3 months. [ Time Frame: 3 months from randomisation ]
   Difference in systolic BP between the intervention and control arms at 3 months
2. The feasibility of telemetric BP lowering in ICH survivors by detection of how many eligible participants agree [ Time Frame: 3 months from randomisation ]
   Feasibility criteria are at least ≥50% of eligible participants agree to participate
3. The feasibility of telemetric BP lowering in ICH survivors by detection of how many drop out in the intervention arm [ Time Frame: 3 months from randomisation ]
   <30% dropout from the intervention arm (discontinuation of home BP monitoring against the advice of the BP monitoring centre) prior to 1 month
4. The feasibility of telemetric BP lowering in ICH survivors by detecting patient approval of the device detected by the acceptability questionnaire [ Time Frame: 3 months from randomisation ]
   Patient approval of the monitoring process in ≥70% of those randomised to the intervention arm.
5. Efficacy of brain imaging by detecting the progression in MRI white matter hyperintensity (WMH) volume over 1 year [ Time Frame: 12 months from randomisation ]
   This will detected in both arms and compared
6. The safety of telemetric BP lowering in ICH survivors measured by serious adverse events [ Time Frame: 12 months from randomisation ]
   Safety is measured by serious adverse events related to reducing BP in the intervention arm

Secondary Outcome Measures :

1. Incidence of recurrent vascular events [ Time Frame: 12 months from randomisation ]
   Any incidence of vascular events reported in both arms
2. Cognitive ability assessed by the Cognitive Assessment (MoCA) questionnaire in both arms [ Time Frame: 12 months from randomisation ]
   The Cognitive Assessment is a questionnaire widely used as a screening assessment for detecting cognitive impairment. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. An abbreviated version of the assessment assessing attention, verbal learning, memory, executive functions/language and orientation can be performed over the phone.
3. The number of BP lowering drugs at 3 months and at 1 year follow-up visits [ Time Frame: 12 months from randomisation ]
   This will detected in both arms and compared
4. mean daytime BP at 1 year on 24-hour ABPM [ Time Frame: 12 months from randomisation ]
   The blood pressure measured in both groups
5. Neuroimaging outcomes: the proportion of patients who develop new cerebral microbleeds (CMBs) over 1 year [ Time Frame: 12 months from randomisation ]
   neuroimaging outcomes will be measured in both arms
6. Neuroimaging outcomes: the proportion of patients who develop new infarcts or intracerebral haemorrhages at 1 year [ Time Frame: 12 months from randomisation ]
   neuroimaging outcomes will be measured in both arms
7. Neuroimaging outcomes: measure change in mean diffusivity (MD) [ Time Frame: 12 months from randomisation ]
   neuroimaging outcomes will be measured in both arms
8. Neuroimaging outcomes: measure fractional anisotropy (FA) [ Time Frame: 12 months from randomisation ]
   neuroimaging outcomes including (but not limited to) ; ; change in mean diffusivity (MD), fractional anisotropy (FA) and other 3T DTI metrics; change in cerebral blood flow (CBF) on 3T PCASL; change in total brain volume, white matter volume and grey matter volume on 3T T1 volumetric images; composite neuroimaging measures (e.g summary SVD scores)
9. Neuroimaging outcomes: measure change in brain volume [ Time Frame: 12 months from randomisation ]
   neuroimaging outcomes including (but not limited to) : change in cerebral blood flow (CBF) on 3T PCASL; change in total brain volume, white matter volume and grey matter volume on 3T T1 volumetric images; composite neuroimaging measures (e.g summary SVD scores)

Eligibility Criteria

• Ages Eligible for Study: 40 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Adults (≥40 years) with spontaneous primary ICH (i.e. without known underlying structural, macrovascular or other cause (e.g. arteriovenous malformation, tumour) after adequate investigation at the discretion of the local investigator). This will include participants presumed to have cerebral SVD (both hypertensive arteriopathy and cerebral amyloid angiopathy)
2. Clinical team opinion that BP control since the ICH is not adequate AND the measured SBP prior to randomisation is ≥130 mm Hg
3. Recruitment soon after ICH, ideally at hospital discharge or within weeks, is encouraged; recruitment at a later stage after ICH is also exceptionally allowed if there is evidence of inadequate BP control AND SBP at randomisation is ≥130 mm Hg
4. For patients recruited in hospital there should be a plan for home discharge (not to a nursing or care home) after their inpatient stay, or living at home at the time of recruitment
5. Willingness and demonstration of ability to undertake home BP measurements, either unassisted or with the help of a relative, friend or carer
6. Ability and willingness to complete an MRI scan
7. Ability and willingness to attend and complete the study assessments including cognitive screen
8. Ability and willingness to provide informed consent, or with a suitable consultee available and able to participate in the intervention (e.g. with a motivated carer)

Exclusion Criteria:

1. Inability to provide informed consent or lack of suitable consultee (if unable to provide personal consent, lack of suitable consultee)
2. Evidence of a macrovascular or structural cause for ICH (e.g. AVM or tumour)
3. Diagnosis of dementia (DSM IV criteria, or self-reported or documented in medical records)
4. Low Functional status (MRS ≥4) before or after ICH or frailty likely to make participation in 1-year follow-up difficult for the participant
5. Life expectancy <2 years
6. Taking more than 2 BP-lowering medications (i.e. 3 or more) at the time of consent
7. Consistently good BP control (below 130/80 mm Hg on measures taken as part of routine clinical care) prior to planned recruitment, judged not to require more intensive treatment
8. Known flow-restricting intracranial/extracranial large arterial stenosis
9. Known contraindication to MRI
10. Known absence of mobile phone coverage from all network operators and home internet at the participant's home
11. Known sensitivity or contra-indication to BP treatments (e.g. symptomatic postural hypotension) is not an absolute exclusion criterion, but more information must be provided
12. Note that participation in other CTIMP or device trial is NOT an automatic exclusion criterion

Contacts and Locations

Contacts

Contact: Shahena Butt; 0203 108 6181; shahena.butt@ucl.ac.uk

Locations

United Kingdom

Cambridge; Recruiting

Cambridge, United Kingdom, CB2 0QQ

Contact: Jobbin Francis jobbin.francis@addenbrookes.nhs.uk

Principal Investigator: Niamh Hannon

Edinburgh; Recruiting

Edinburgh, United Kingdom, EH16 4SB

Contact: Allan Macraild allan.macraild@nhslothian.scot.nhs.uk

Principal Investigator: Rustam Al-Shahi Salman

Glasgow; Recruiting

Glasgow, United Kingdom, G51 4TF

Contact: Angela Welch angelawelch@nhs.net

Principal Investigator: Keith Muir

King's; Recruiting

London, United Kingdom, SE5 8AF

Contact: Maria Tibajia mtibajia@nhs.net

Principal Investigator: Dulka Manawadu

St George's; Recruiting

London, United Kingdom, SW17 0QT

Contact: Sarah Stratton sarah.stratton@nhs.net

Principal Investigator: Liqun Zhang

Imperial; Recruiting

London, United Kingdom, W12 0HS

Contact: Peter Wilding peter.wilding@nhs.net

Principal Investigator: Soma Banerjee

UCLH; Recruiting

London, United Kingdom, WC1B 5EH

Contact: Anna Robinson anna.robinson7@nhs.net

Principal Investigator: David Werring

Nottingham; Recruiting

Nottingham, United Kingdom, NG5 1PB

Contact: Gwendoline Wilkes Gwendoline.wilkes@nottingham.ac.uk

Principal Investigator: Kailash Krishnan

Oxford; Recruiting

Oxford, United Kingdom, OX3 9DU

Contact: Michelle Wilson michelle.wilson@ndcn.ox.ac.uk

Principal Investigator: Peter Rothwell

Royal Preston; Recruiting

Preston, United Kingdom, PR2 9HT

Contact: Heather Adams Heather.ADAMS@lthtr.nhs.uk

Principal Investigator: Hedley Emsley

Salford; Recruiting

Salford, United Kingdom, M6 8HD

Contact: Stephanie Lee Stephanie.Lee@srft.nhs.uk

Principal Investigator: Adrian Parry-Jones

Sheffield; Recruiting

Sheffield, United Kingdom, S10 2JF

Contact: Emma Richards Emma.Richards@sth.nhs.uk

Principal Investigator: Kirsty Harkness

Sponsors and Collaborators

University College, London

Investigators

• Study Chair: David Werring; University College, London

  Study Documents (Full-Text)

Documents provided by University College, London:

Study Protocol  [PDF] June 13, 2018

More Information

• Responsible Party: University College, London
• ClinicalTrials.gov Identifier: NCT03863665
• Other Study ID Numbers: PROHIBIT-ICH01
• First Posted: March 5, 2019
• Last Update Posted: April 17, 2019
• Last Verified: April 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Cerebral Hemorrhage; Hemorrhage; Pathologic Processes; Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases