NCT02481323

Brief Summary

Phase II pilot randomised, factorial, short term dose escalation, open label, blinded intermediary endpoint trial, in two hospital centres in the UK, of tolerability and safety of cilostazol, isosorbide mononitrate, both or neither in patients with small vessel disease manifest as symptomatic small subcortical stroke.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
57

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Mar 2016

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 19, 2015

Completed
6 days until next milestone

First Posted

Study publicly available on registry

June 25, 2015

Completed
8 months until next milestone

Study Start

First participant enrolled

March 1, 2016

Completed
1.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2017

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 30, 2017

Completed
Last Updated

January 19, 2018

Status Verified

January 1, 2018

Enrollment Period

1.4 years

First QC Date

June 19, 2015

Last Update Submit

January 18, 2018

Conditions

Keywords

cerebral small vessel diseasecerebrovascular reactivitycilostazolisosorbide mononitrate

Outcome Measures

Primary Outcomes (1)

  • Tolerability proportion of patients able to tolerate the target dose

    proportion of patients able to tolerate the target dose

    8 weeks

Secondary Outcomes (13)

  • Safety - bleeding

    12 weeks

  • Safety - recurrent stroke

    12 weeks

  • Safety - death

    12 weeks

  • Safety - blood pressure

    8 weeks

  • Safety - bleeding

    8 weeks

  • +8 more secondary outcomes

Study Arms (4)

Group 1

ACTIVE COMPARATOR

Isosorbide mononitrate 25mg bd

Drug: isosorbide mononitrate

Group 2

ACTIVE COMPARATOR

Cilostazol 100mg bd

Drug: cilostazol

Group 3

ACTIVE COMPARATOR

Isosorbide mononitrate 25mg bd and cilostazol 100mg bd start immediately

Drug: isosorbide mononitrateDrug: cilostazol

Group 4

OTHER

Isosorbide mononitrate 25mg bd and cilostazol 100mg bd delayed start

Drug: isosorbide mononitrateDrug: cilostazol

Interventions

slow release nitric oxide donor that enhances vasodilation and widely used in angina prophyaxis

Also known as: Isotard
Group 1Group 3Group 4

phosphodiesterase 3-inhibitor that enhances vessel wall function with weak antiplatelet effects

Also known as: pletal
Group 2Group 3Group 4

Eligibility Criteria

Age35 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Mild symptomatic ischaemic stroke in the past four years compatible with a clinical lacunar stroke syndrome, with brain magnetic resonance imaging or computed tomography scanning that is compatible with a symptomatic small subcortical (lacunar) infarct, or if no recent relevant infarct is visible, that excluded other cause for symptoms
  • Age \> 35 years
  • Independent in activities of daily living (modified Rankin ≤2)
  • Able to give consent themselves

You may not qualify if:

  • Other significant active neurological illness present since suffering stroke (eg seizures, multiple sclerosis, brain tumour)
  • Age \< 35
  • Montreal Cognitive Assessment score \<26
  • Requiring assistance with activities of daily living (Modified Rankin ≥3)
  • Active cardiac disease (atrial fibrillation, myocardial infarction in past 6 months, active angina, symptomatic cardiac failure)
  • Definite indication for, or definite contraindication to either trial drug
  • Unable to swallow
  • Bleeding tendency (platelets\<100, taking anticoagulant medication)
  • Unlikely to comply with trial medication
  • Planned surgery during the trial period
  • History of intracranial haemorrhage (subdural haematoma, subarachnoid haemorrhage, intracerebral haemorrhage, but not asymptomatic haemorrhagic transformation of infarction)
  • Other life threatening illness
  • History of drug overdose or attempted suicide or significant active mental illness
  • Pregnancy
  • If recruited in Edinburgh and participating in cerebrovascular reactivity arm of trial: active respiratory illness (such as moderate to severe asthma or chronic obstructive airways disease), unable to tolerate magnetic resonance imaging or unable to lie flat

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

University of Edinburgh

Edinburgh, EH4 2XU, United Kingdom

Location

University of Nottingham

Nottingham, NG7 2RD, United Kingdom

Location

Related Publications (1)

  • Blair GW, Janssen E, Stringer MS, Thrippleton MJ, Chappell F, Shi Y, Hamilton I, Flaherty K, Appleton JP, Doubal FN, Bath PM, Wardlaw JM. Effects of Cilostazol and Isosorbide Mononitrate on Cerebral Hemodynamics in the LACI-1 Randomized Controlled Trial. Stroke. 2022 Jan;53(1):29-33. doi: 10.1161/STROKEAHA.121.034866. Epub 2021 Dec 1.

MeSH Terms

Conditions

Cerebral Small Vessel DiseasesCognitive DysfunctionStroke

Interventions

isosorbide-5-mononitrateCilostazol

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesCognition DisordersNeurocognitive DisordersMental Disorders

Intervention Hierarchy (Ancestors)

TetrazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsQuinolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-Ring

Study Officials

  • Joanna M Wardlaw, MD

    University of Edinburgh

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
FACTORIAL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 19, 2015

First Posted

June 25, 2015

Study Start

March 1, 2016

Primary Completion

August 1, 2017

Study Completion

November 30, 2017

Last Updated

January 19, 2018

Record last verified: 2018-01

Data Sharing

IPD Sharing
Will not share

Locations