Trial Outcomes & Findings for LACunar Intervention (LACI-2) Trial-2 (NCT NCT03451591)
NCT ID: NCT03451591
Last Updated: 2024-11-12
Results Overview
Feasibility of Phase III trial, i.e. that eligible patients can be identified correctly, in sufficient numbers, enrolled and \>95% retained in follow-up at one year, to achieve feasibility target sample size recruitment and randomisation of 400 patients in 24 months in the UK.
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
363 participants
Primary outcome timeframe
36 months (24 Months Recruitment + 12 months Follow Up)
Results posted on
2024-11-12
Participant Flow
Participant milestones
| Measure |
Isosorbide Mononitrate XL (ISMN)
Oral Isotard® 25mg XL (Isosorbide Mononitrate) tablets. Oral Isotard® 25mg XL: Day 1-5 / 25mg daily morning dose. Day 6 to week 52 / 50mg daily morning dose. Week 53 / 25mg daily morning dose. Week 54 / NIL dose. Or Oral Isosorbide mononitrate (ISMN) non-XL 20mg tablets: Day 1-5 / 20mg daily evening dose. Day 6 to week 52 / 20mg twice daily morning \& evening. Week 53 / 20mg daily morning dose. Week 54 / NIL dose.
Isosorbide Mononitrate XL (ISMN): Isosorbide mononitrate (ISMN), is an NO donating organic nitrate that enhances vasodilation, is widely used in ischaemic heart disease, and has no antiplatelet activity.
|
Cilostazol
Oral Cilostazol 100mg tablets. Day 1-5 / 50mg daily evening dose. Day 6-10 / 50mg twice daily morning \& evening. Day 11-15 / 50mg daily morning dose \& 100mg daily evening dose. Day 16 to week 52 / 100mg twice daily morning \& evening. Week 53 / 50mg twice daily morning \& evening. Week 54 / NIL dose.
Cilostazol: Cilostazol is a phosphodiesterase 3-inhibitor (PDE3-inhibitor) that enhances the PGI2-cAMP system. It has weak antiplatelet effects (so low bleeding risk), reduces infarct size and reduces ageing-related decline in myelin repair in experimental models.
|
ISMN XL and Cilostazol
Oral Isotard® 25 mg XL (ISMN) and oral Cilostazol 100mg tablets. Day 1-5 / ISMN - 25mg daily evening dose / Cilostazol - NIL. Day 6-10 / ISMN - 50mg daily morning dose and Cilostazol - NIL. Day 11-15 / ISMN - 50mg daily morning dose / Cilostazol - 50mg daily evening dose. Day 16-20 / ISMN - 50mg daily morning dose and Cilostazol - 50mg twice daily morning \& evening. Day 21-25 / ISMN - 50mg daily morning dose and Cilostazol - twice daily, 50mg morning \& 100mg evening dose. Day 26-30 ISMN - 50mg daily morning dose and Cilostazol 100mg - twice daily morning \& evening. Day 30 to week 52 / ISMN 50mg morning dose and Cilostazol 100mg - twice daily morning \& evening. Week 53 / ISMN 25mg daily morning dose and Cilostazol 50mg twice daily morning \& evening. Week 54 / NIL dose
ISMN XL and Cilostazol: Cilostazol is a phosphodiesterase 3-inhibitor (PDE3-inhibitor) that enhances the PGI2-cAMP system. It has weak antiplatelet effects (so low bleeding risk), reduces infarct size and reduces ageing-related decline in myelin repair in experimental models. Isosorbide mononitrate (ISMN), is an NO donating organic nitrate that enhances vasodilation, is widely used in ischaemic heart disease, and has no antiplatelet activity.
|
Neither ISMN Nor Cilostazol
Neither isosorbide mononitrate nor Cilostazol is administered for the entire duration of the study.
Neither ISMN nor cilostazol: Neither isosorbide mononitrate nor Cilostazol administered for the entire duration of the study.
|
|---|---|---|---|---|
|
Randomisation
STARTED
|
90
|
91
|
91
|
91
|
|
Randomisation
COMPLETED
|
90
|
91
|
91
|
91
|
|
Randomisation
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
SAE Reporting - Exposure to IMP
STARTED
|
181
|
182
|
91
|
91
|
|
SAE Reporting - Exposure to IMP
COMPLETED
|
181
|
182
|
91
|
91
|
|
SAE Reporting - Exposure to IMP
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Randomisation to 12 Month Follow Up
STARTED
|
90
|
91
|
91
|
91
|
|
Randomisation to 12 Month Follow Up
COMPLETED
|
70
|
70
|
81
|
87
|
|
Randomisation to 12 Month Follow Up
NOT COMPLETED
|
20
|
21
|
10
|
4
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Isosorbide Mononitrate XL (ISMN)
n=90 Participants
Oral Isotard® 25mg XL (Isosorbide Mononitrate) tablets. Oral Isotard® 25mg XL: Day 1-5 / 25mg daily morning dose. Day 6 to week 52 / 50mg daily morning dose. Week 53 / 25mg daily morning dose. Week 54 / NIL dose. Or Oral Isosorbide mononitrate (ISMN) non-XL 20mg tablets: Day 1-5 / 20mg daily evening dose. Day 6 to week 52 / 20mg twice daily morning \& evening. Week 53 / 20mg daily morning dose. Week 54 / NIL dose.
Isosorbide Mononitrate XL (ISMN): Isosorbide mononitrate (ISMN), is an NO donating organic nitrate that enhances vasodilation, is widely used in ischaemic heart disease, and has no antiplatelet activity.
|
Cilostazol
n=91 Participants
Oral Cilostazol 100mg tablets. Day 1-5 / 50mg daily evening dose. Day 6-10 / 50mg twice daily morning \& evening. Day 11-15 / 50mg daily morning dose \& 100mg daily evening dose. Day 16 to week 52 / 100mg twice daily morning \& evening. Week 53 / 50mg twice daily morning \& evening. Week 54 / NIL dose.
Cilostazol: Cilostazol is a phosphodiesterase 3-inhibitor (PDE3-inhibitor) that enhances the PGI2-cAMP system. It has weak antiplatelet effects (so low bleeding risk), reduces infarct size and reduces ageing-related decline in myelin repair in experimental models.
|
ISMN XL and Cilostazol
n=91 Participants
Oral Isotard® 25 mg XL (ISMN) and oral Cilostazol 100mg tablets. Day 1-5 / ISMN - 25mg daily evening dose / Cilostazol - NIL. Day 6-10 / ISMN - 50mg daily morning dose and Cilostazol - NIL. Day 11-15 / ISMN - 50mg daily morning dose / Cilostazol - 50mg daily evening dose. Day 16-20 / ISMN - 50mg daily morning dose and Cilostazol - 50mg twice daily morning \& evening. Day 21-25 / ISMN - 50mg daily morning dose and Cilostazol - twice daily, 50mg morning \& 100mg evening dose. Day 26-30 ISMN - 50mg daily morning dose and Cilostazol 100mg - twice daily morning \& evening. Day 30 to week 52 / ISMN 50mg morning dose and Cilostazol 100mg - twice daily morning \& evening. Week 53 / ISMN 25mg daily morning dose and Cilostazol 50mg twice daily morning \& evening. Week 54 / NIL dose
ISMN XL and Cilostazol: Cilostazol is a phosphodiesterase 3-inhibitor (PDE3-inhibitor) that enhances the PGI2-cAMP system. It has weak antiplatelet effects (so low bleeding risk), reduces infarct size and reduces ageing-related decline in myelin repair in experimental models. Isosorbide mononitrate (ISMN), is an NO donating organic nitrate that enhances vasodilation, is widely used in ischaemic heart disease, and has no antiplatelet activity.
|
Neither ISMN Nor Cilostazol
n=91 Participants
Neither isosorbide mononitrate nor Cilostazol is administered for the entire duration of the study.
Neither ISMN nor cilostazol: Neither isosorbide mononitrate nor Cilostazol administered for the entire duration of the study.
|
Total
n=363 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
65 years
n=90 Participants
|
64 years
n=91 Participants
|
63 years
n=91 Participants
|
64 years
n=91 Participants
|
64 years
n=363 Participants
|
|
Sex: Female, Male
Female
|
27 Participants
n=90 Participants
|
28 Participants
n=91 Participants
|
27 Participants
n=91 Participants
|
30 Participants
n=91 Participants
|
112 Participants
n=363 Participants
|
|
Sex: Female, Male
Male
|
63 Participants
n=90 Participants
|
63 Participants
n=91 Participants
|
64 Participants
n=91 Participants
|
61 Participants
n=91 Participants
|
251 Participants
n=363 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Stroke onset to randomisation, days
|
223.8 days
STANDARD_DEVIATION 409.8 • n=90 Participants
|
217.8 days
STANDARD_DEVIATION 456.7 • n=91 Participants
|
263.9 days
STANDARD_DEVIATION 614.7 • n=91 Participants
|
192.9 days
STANDARD_DEVIATION 270.3 • n=91 Participants
|
224.6 days
STANDARD_DEVIATION 453.8 • n=363 Participants
|
|
Stroke onset to randomisation <=100 days
|
54 Participants
n=90 Participants
|
53 Participants
n=91 Participants
|
46 Participants
n=91 Participants
|
53 Participants
n=91 Participants
|
206 Participants
n=363 Participants
|
|
Highest education level - postgraduate
|
5 Participants
n=90 Participants
|
6 Participants
n=91 Participants
|
10 Participants
n=91 Participants
|
6 Participants
n=91 Participants
|
27 Participants
n=363 Participants
|
|
Highest education level - undergraduate
|
8 Participants
n=90 Participants
|
9 Participants
n=91 Participants
|
9 Participants
n=91 Participants
|
11 Participants
n=91 Participants
|
37 Participants
n=363 Participants
|
|
Highest education level - A Level or Equivalent
|
8 Participants
n=90 Participants
|
14 Participants
n=91 Participants
|
14 Participants
n=91 Participants
|
18 Participants
n=91 Participants
|
54 Participants
n=363 Participants
|
|
Highest education level - O-level/GCSE or equivalent
|
34 Participants
n=90 Participants
|
30 Participants
n=91 Participants
|
27 Participants
n=91 Participants
|
23 Participants
n=91 Participants
|
114 Participants
n=363 Participants
|
|
Highest education level - Secondary School
|
34 Participants
n=90 Participants
|
32 Participants
n=91 Participants
|
31 Participants
n=91 Participants
|
32 Participants
n=91 Participants
|
129 Participants
n=363 Participants
|
|
Highest education level - Primary School
|
1 Participants
n=90 Participants
|
0 Participants
n=91 Participants
|
0 Participants
n=91 Participants
|
1 Participants
n=91 Participants
|
2 Participants
n=363 Participants
|
|
Systolic Blood Pressure
|
145 mmHg
STANDARD_DEVIATION 18.1 • n=90 Participants
|
145.2 mmHg
STANDARD_DEVIATION 20.6 • n=91 Participants
|
145.1 mmHg
STANDARD_DEVIATION 19.3 • n=91 Participants
|
142.7 mmHg
STANDARD_DEVIATION 20.1 • n=91 Participants
|
144.5 mmHg
STANDARD_DEVIATION 19.5 • n=363 Participants
|
PRIMARY outcome
Timeframe: 36 months (24 Months Recruitment + 12 months Follow Up)Population: Number of participants at 12 months who did not complete follow up - because they refused, were lost to follow up or withdrawn
Feasibility of Phase III trial, i.e. that eligible patients can be identified correctly, in sufficient numbers, enrolled and \>95% retained in follow-up at one year, to achieve feasibility target sample size recruitment and randomisation of 400 patients in 24 months in the UK.
Outcome measures
| Measure |
Isosorbide Mononitrate XL (ISMN)
n=90 Participants
Oral Isotard® 25mg XL (Isosorbide Mononitrate) tablets. Oral Isotard® 25mg XL: Day 1-5 / 25mg daily morning dose. Day 6 to week 52 / 50mg daily morning dose. Week 53 / 25mg daily morning dose. Week 54 / NIL dose. Or Oral Isosorbide mononitrate (ISMN) non-XL 20mg tablets: Day 1-5 / 20mg daily evening dose. Day 6 to week 52 / 20mg twice daily morning \& evening. Week 53 / 20mg daily morning dose. Week 54 / NIL dose.
Isosorbide Mononitrate XL (ISMN): Isosorbide mononitrate (ISMN), is an NO donating organic nitrate that enhances vasodilation, is widely used in ischaemic heart disease, and has no antiplatelet activity.
|
Cilostazol
n=91 Participants
Oral Cilostazol 100mg tablets. Day 1-5 / 50mg daily evening dose. Day 6-10 / 50mg twice daily morning \& evening. Day 11-15 / 50mg daily morning dose \& 100mg daily evening dose. Day 16 to week 52 / 100mg twice daily morning \& evening. Week 53 / 50mg twice daily morning \& evening. Week 54 / NIL dose.
Cilostazol: Cilostazol is a phosphodiesterase 3-inhibitor (PDE3-inhibitor) that enhances the PGI2-cAMP system. It has weak antiplatelet effects (so low bleeding risk), reduces infarct size and reduces ageing-related decline in myelin repair in experimental models.
|
ISMN XL and Cilostazol
n=91 Participants
Oral Isotard® 25 mg XL (ISMN) and oral Cilostazol 100mg tablets. Day 1-5 / ISMN - 25mg daily evening dose / Cilostazol - NIL. Day 6-10 / ISMN - 50mg daily morning dose and Cilostazol - NIL. Day 11-15 / ISMN - 50mg daily morning dose / Cilostazol - 50mg daily evening dose. Day 16-20 / ISMN - 50mg daily morning dose and Cilostazol - 50mg twice daily morning \& evening. Day 21-25 / ISMN - 50mg daily morning dose and Cilostazol - twice daily, 50mg morning \& 100mg evening dose. Day 26-30 ISMN - 50mg daily morning dose and Cilostazol 100mg - twice daily morning \& evening. Day 30 to week 52 / ISMN 50mg morning dose and Cilostazol 100mg - twice daily morning \& evening. Week 53 / ISMN 25mg daily morning dose and Cilostazol 50mg twice daily morning \& evening. Week 54 / NIL dose
ISMN XL and Cilostazol: Cilostazol is a phosphodiesterase 3-inhibitor (PDE3-inhibitor) that enhances the PGI2-cAMP system. It has weak antiplatelet effects (so low bleeding risk), reduces infarct size and reduces ageing-related decline in myelin repair in experimental models. Isosorbide mononitrate (ISMN), is an NO donating organic nitrate that enhances vasodilation, is widely used in ischaemic heart disease, and has no antiplatelet activity.
|
Neither ISMN Nor Cilostazol
n=91 Participants
Neither isosorbide mononitrate nor Cilostazol is administered for the entire duration of the study.
Neither ISMN nor cilostazol: Neither isosorbide mononitrate nor Cilostazol administered for the entire duration of the study.
|
|---|---|---|---|---|
|
Feasibility of Phase III Trial
|
20 Participants
|
21 Participants
|
10 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Adherence to medication at half dose or more at 1 year
It is estimated that in this trial 75% of patients will be able to tolerate trial medication, in at least half dose, up to one year after randomisation (i.e. less than 25% will stop trial medication completely through inability to tolerate the drugs).
Outcome measures
| Measure |
Isosorbide Mononitrate XL (ISMN)
n=90 Participants
Oral Isotard® 25mg XL (Isosorbide Mononitrate) tablets. Oral Isotard® 25mg XL: Day 1-5 / 25mg daily morning dose. Day 6 to week 52 / 50mg daily morning dose. Week 53 / 25mg daily morning dose. Week 54 / NIL dose. Or Oral Isosorbide mononitrate (ISMN) non-XL 20mg tablets: Day 1-5 / 20mg daily evening dose. Day 6 to week 52 / 20mg twice daily morning \& evening. Week 53 / 20mg daily morning dose. Week 54 / NIL dose.
Isosorbide Mononitrate XL (ISMN): Isosorbide mononitrate (ISMN), is an NO donating organic nitrate that enhances vasodilation, is widely used in ischaemic heart disease, and has no antiplatelet activity.
|
Cilostazol
n=91 Participants
Oral Cilostazol 100mg tablets. Day 1-5 / 50mg daily evening dose. Day 6-10 / 50mg twice daily morning \& evening. Day 11-15 / 50mg daily morning dose \& 100mg daily evening dose. Day 16 to week 52 / 100mg twice daily morning \& evening. Week 53 / 50mg twice daily morning \& evening. Week 54 / NIL dose.
Cilostazol: Cilostazol is a phosphodiesterase 3-inhibitor (PDE3-inhibitor) that enhances the PGI2-cAMP system. It has weak antiplatelet effects (so low bleeding risk), reduces infarct size and reduces ageing-related decline in myelin repair in experimental models.
|
ISMN XL and Cilostazol
n=91 Participants
Oral Isotard® 25 mg XL (ISMN) and oral Cilostazol 100mg tablets. Day 1-5 / ISMN - 25mg daily evening dose / Cilostazol - NIL. Day 6-10 / ISMN - 50mg daily morning dose and Cilostazol - NIL. Day 11-15 / ISMN - 50mg daily morning dose / Cilostazol - 50mg daily evening dose. Day 16-20 / ISMN - 50mg daily morning dose and Cilostazol - 50mg twice daily morning \& evening. Day 21-25 / ISMN - 50mg daily morning dose and Cilostazol - twice daily, 50mg morning \& 100mg evening dose. Day 26-30 ISMN - 50mg daily morning dose and Cilostazol 100mg - twice daily morning \& evening. Day 30 to week 52 / ISMN 50mg morning dose and Cilostazol 100mg - twice daily morning \& evening. Week 53 / ISMN 25mg daily morning dose and Cilostazol 50mg twice daily morning \& evening. Week 54 / NIL dose
ISMN XL and Cilostazol: Cilostazol is a phosphodiesterase 3-inhibitor (PDE3-inhibitor) that enhances the PGI2-cAMP system. It has weak antiplatelet effects (so low bleeding risk), reduces infarct size and reduces ageing-related decline in myelin repair in experimental models. Isosorbide mononitrate (ISMN), is an NO donating organic nitrate that enhances vasodilation, is widely used in ischaemic heart disease, and has no antiplatelet activity.
|
Neither ISMN Nor Cilostazol
Neither isosorbide mononitrate nor Cilostazol is administered for the entire duration of the study.
Neither ISMN nor cilostazol: Neither isosorbide mononitrate nor Cilostazol administered for the entire duration of the study.
|
|---|---|---|---|---|
|
Trial Medication Tolerability Measured by Number of Participants With Adherence to Medication at Half Dose or More at 1 Year
|
59 Participants
|
48 Participants
|
45 Participants
|
—
|
SECONDARY outcome
Timeframe: 12 monthsSafety - symptoms of systemic or intracranial bleeding, recurrent cerebral and systemic vascular events, and vascular and non-vascular causes of death will be collected. It is estimated that in this trial the absolute risk of death, including fatal haemorrhage, will not differ significantly (ie fall outside the upper 95% CI) from 2% per year on trial drugs versus no trial drugs, when given in addition to guideline drugs; and will not increase bleeding or ischaemic SVD lesions significantly (at the p\<0.01 level) on MRI.
Outcome measures
| Measure |
Isosorbide Mononitrate XL (ISMN)
n=90 Participants
Oral Isotard® 25mg XL (Isosorbide Mononitrate) tablets. Oral Isotard® 25mg XL: Day 1-5 / 25mg daily morning dose. Day 6 to week 52 / 50mg daily morning dose. Week 53 / 25mg daily morning dose. Week 54 / NIL dose. Or Oral Isosorbide mononitrate (ISMN) non-XL 20mg tablets: Day 1-5 / 20mg daily evening dose. Day 6 to week 52 / 20mg twice daily morning \& evening. Week 53 / 20mg daily morning dose. Week 54 / NIL dose.
Isosorbide Mononitrate XL (ISMN): Isosorbide mononitrate (ISMN), is an NO donating organic nitrate that enhances vasodilation, is widely used in ischaemic heart disease, and has no antiplatelet activity.
|
Cilostazol
n=91 Participants
Oral Cilostazol 100mg tablets. Day 1-5 / 50mg daily evening dose. Day 6-10 / 50mg twice daily morning \& evening. Day 11-15 / 50mg daily morning dose \& 100mg daily evening dose. Day 16 to week 52 / 100mg twice daily morning \& evening. Week 53 / 50mg twice daily morning \& evening. Week 54 / NIL dose.
Cilostazol: Cilostazol is a phosphodiesterase 3-inhibitor (PDE3-inhibitor) that enhances the PGI2-cAMP system. It has weak antiplatelet effects (so low bleeding risk), reduces infarct size and reduces ageing-related decline in myelin repair in experimental models.
|
ISMN XL and Cilostazol
n=91 Participants
Oral Isotard® 25 mg XL (ISMN) and oral Cilostazol 100mg tablets. Day 1-5 / ISMN - 25mg daily evening dose / Cilostazol - NIL. Day 6-10 / ISMN - 50mg daily morning dose and Cilostazol - NIL. Day 11-15 / ISMN - 50mg daily morning dose / Cilostazol - 50mg daily evening dose. Day 16-20 / ISMN - 50mg daily morning dose and Cilostazol - 50mg twice daily morning \& evening. Day 21-25 / ISMN - 50mg daily morning dose and Cilostazol - twice daily, 50mg morning \& 100mg evening dose. Day 26-30 ISMN - 50mg daily morning dose and Cilostazol 100mg - twice daily morning \& evening. Day 30 to week 52 / ISMN 50mg morning dose and Cilostazol 100mg - twice daily morning \& evening. Week 53 / ISMN 25mg daily morning dose and Cilostazol 50mg twice daily morning \& evening. Week 54 / NIL dose
ISMN XL and Cilostazol: Cilostazol is a phosphodiesterase 3-inhibitor (PDE3-inhibitor) that enhances the PGI2-cAMP system. It has weak antiplatelet effects (so low bleeding risk), reduces infarct size and reduces ageing-related decline in myelin repair in experimental models. Isosorbide mononitrate (ISMN), is an NO donating organic nitrate that enhances vasodilation, is widely used in ischaemic heart disease, and has no antiplatelet activity.
|
Neither ISMN Nor Cilostazol
n=91 Participants
Neither isosorbide mononitrate nor Cilostazol is administered for the entire duration of the study.
Neither ISMN nor cilostazol: Neither isosorbide mononitrate nor Cilostazol administered for the entire duration of the study.
|
|---|---|---|---|---|
|
Incidence of Treatment Emergent Adverse Effects [Safety]
|
1 Participants
|
2 Participants
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Clinical, functional, QoL and global outcomes at 12 months- Stroke/TIA, MI, Cognitive impairment, Dependency, Death. Data are number (%)
It is estimated that in this trial the combined rate of recurrent stroke, MI, death, cognitive impairment and dependency will be 40-50% at one year after enrolment in order to detect modest but clinically-important reductions in poor outcomes. The study has a 2x2 partial factorial design. This allows testing of both drugs when given alone and together. Participants were allocated into one of four treatment groups. However, as some participants were in a group which received both treatments simultaneously then the subgroups reported for IMP exposure include a count of both participants from the single and the combined treatment groups as the total number exposed to that IMP
Outcome measures
| Measure |
Isosorbide Mononitrate XL (ISMN)
n=181 Participants
Oral Isotard® 25mg XL (Isosorbide Mononitrate) tablets. Oral Isotard® 25mg XL: Day 1-5 / 25mg daily morning dose. Day 6 to week 52 / 50mg daily morning dose. Week 53 / 25mg daily morning dose. Week 54 / NIL dose. Or Oral Isosorbide mononitrate (ISMN) non-XL 20mg tablets: Day 1-5 / 20mg daily evening dose. Day 6 to week 52 / 20mg twice daily morning \& evening. Week 53 / 20mg daily morning dose. Week 54 / NIL dose.
Isosorbide Mononitrate XL (ISMN): Isosorbide mononitrate (ISMN), is an NO donating organic nitrate that enhances vasodilation, is widely used in ischaemic heart disease, and has no antiplatelet activity.
|
Cilostazol
n=182 Participants
Oral Cilostazol 100mg tablets. Day 1-5 / 50mg daily evening dose. Day 6-10 / 50mg twice daily morning \& evening. Day 11-15 / 50mg daily morning dose \& 100mg daily evening dose. Day 16 to week 52 / 100mg twice daily morning \& evening. Week 53 / 50mg twice daily morning \& evening. Week 54 / NIL dose.
Cilostazol: Cilostazol is a phosphodiesterase 3-inhibitor (PDE3-inhibitor) that enhances the PGI2-cAMP system. It has weak antiplatelet effects (so low bleeding risk), reduces infarct size and reduces ageing-related decline in myelin repair in experimental models.
|
ISMN XL and Cilostazol
n=89 Participants
Oral Isotard® 25 mg XL (ISMN) and oral Cilostazol 100mg tablets. Day 1-5 / ISMN - 25mg daily evening dose / Cilostazol - NIL. Day 6-10 / ISMN - 50mg daily morning dose and Cilostazol - NIL. Day 11-15 / ISMN - 50mg daily morning dose / Cilostazol - 50mg daily evening dose. Day 16-20 / ISMN - 50mg daily morning dose and Cilostazol - 50mg twice daily morning \& evening. Day 21-25 / ISMN - 50mg daily morning dose and Cilostazol - twice daily, 50mg morning \& 100mg evening dose. Day 26-30 ISMN - 50mg daily morning dose and Cilostazol 100mg - twice daily morning \& evening. Day 30 to week 52 / ISMN 50mg morning dose and Cilostazol 100mg - twice daily morning \& evening. Week 53 / ISMN 25mg daily morning dose and Cilostazol 50mg twice daily morning \& evening. Week 54 / NIL dose
ISMN XL and Cilostazol: Cilostazol is a phosphodiesterase 3-inhibitor (PDE3-inhibitor) that enhances the PGI2-cAMP system. It has weak antiplatelet effects (so low bleeding risk), reduces infarct size and reduces ageing-related decline in myelin repair in experimental models. Isosorbide mononitrate (ISMN), is an NO donating organic nitrate that enhances vasodilation, is widely used in ischaemic heart disease, and has no antiplatelet activity.
|
Neither ISMN Nor Cilostazol
n=91 Participants
Neither isosorbide mononitrate nor Cilostazol is administered for the entire duration of the study.
Neither ISMN nor cilostazol: Neither isosorbide mononitrate nor Cilostazol administered for the entire duration of the study.
|
|---|---|---|---|---|
|
Treatment Efficacy - Percentage of Participants Experiencing an Event (Stroke, TIA, Myocardial Ischaemia, Cognitive Impairment and Dementia)
|
80 Participants
|
84 Participants
|
36 Participants
|
55 Participants
|
Adverse Events
Isosorbide Mononitrate XL (ISMN)
Serious events: 21 serious events
Other events: 0 other events
Deaths: 1 deaths
Cilostazol
Serious events: 29 serious events
Other events: 0 other events
Deaths: 1 deaths
ISMN XL and Cilostazol
Serious events: 15 serious events
Other events: 0 other events
Deaths: 0 deaths
Neither ISMN Nor Cilostazol
Serious events: 12 serious events
Other events: 0 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Isosorbide Mononitrate XL (ISMN)
n=181 participants at risk
Oral Isotard® 25mg XL (Isosorbide Mononitrate) tablets. Oral Isotard® 25mg XL: Day 1-5 / 25mg daily morning dose. Day 6 to week 52 / 50mg daily morning dose. Week 53 / 25mg daily morning dose. Week 54 / NIL dose. Or Oral Isosorbide mononitrate (ISMN) non-XL 20mg tablets: Day 1-5 / 20mg daily evening dose. Day 6 to week 52 / 20mg twice daily morning \& evening. Week 53 / 20mg daily morning dose. Week 54 / NIL dose.
Isosorbide Mononitrate XL (ISMN): Isosorbide mononitrate (ISMN), is an NO donating organic nitrate that enhances vasodilation, is widely used in ischaemic heart disease, and has no antiplatelet activity.
|
Cilostazol
n=182 participants at risk
Oral Cilostazol 100mg tablets. Day 1-5 / 50mg daily evening dose. Day 6-10 / 50mg twice daily morning \& evening. Day 11-15 / 50mg daily morning dose \& 100mg daily evening dose. Day 16 to week 52 / 100mg twice daily morning \& evening. Week 53 / 50mg twice daily morning \& evening. Week 54 / NIL dose.
Cilostazol: Cilostazol is a phosphodiesterase 3-inhibitor (PDE3-inhibitor) that enhances the PGI2-cAMP system. It has weak antiplatelet effects (so low bleeding risk), reduces infarct size and reduces ageing-related decline in myelin repair in experimental models.
|
ISMN XL and Cilostazol
n=91 participants at risk
Oral Isotard® 25 mg XL (ISMN) and oral Cilostazol 100mg tablets. Day 1-5 / ISMN - 25mg daily evening dose / Cilostazol - NIL. Day 6-10 / ISMN - 50mg daily morning dose and Cilostazol - NIL. Day 11-15 / ISMN - 50mg daily morning dose / Cilostazol - 50mg daily evening dose. Day 16-20 / ISMN - 50mg daily morning dose and Cilostazol - 50mg twice daily morning \& evening. Day 21-25 / ISMN - 50mg daily morning dose and Cilostazol - twice daily, 50mg morning \& 100mg evening dose. Day 26-30 ISMN - 50mg daily morning dose and Cilostazol 100mg - twice daily morning \& evening. Day 30 to week 52 / ISMN 50mg morning dose and Cilostazol 100mg - twice daily morning \& evening. Week 53 / ISMN 25mg daily morning dose and Cilostazol 50mg twice daily morning \& evening. Week 54 / NIL dose
ISMN XL and Cilostazol: Cilostazol is a phosphodiesterase 3-inhibitor (PDE3-inhibitor) that enhances the PGI2-cAMP system. It has weak antiplatelet effects (so low bleeding risk), reduces infarct size and reduces ageing-related decline in myelin repair in experimental models. Isosorbide mononitrate (ISMN), is an NO donating organic nitrate that enhances vasodilation, is widely used in ischaemic heart disease, and has no antiplatelet activity.
|
Neither ISMN Nor Cilostazol
n=91 participants at risk
Neither isosorbide mononitrate nor Cilostazol is administered for the entire duration of the study.
Neither ISMN nor cilostazol: Neither isosorbide mononitrate nor Cilostazol administered for the entire duration of the study.
|
|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Respiratory
|
0.55%
1/181 • Number of events 1 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
1.1%
2/182 • Number of events 2 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
1.1%
1/91 • Number of events 1 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
1.1%
1/91 • Number of events 1 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
|
Gastrointestinal disorders
Gastrointestinal
|
3.9%
7/181 • Number of events 7 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
4.4%
8/182 • Number of events 8 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
5.5%
5/91 • Number of events 5 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
1.1%
1/91 • Number of events 1 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
|
Renal and urinary disorders
Genitourinary
|
0.55%
1/181 • Number of events 1 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
2.2%
4/182 • Number of events 4 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
1.1%
1/91 • Number of events 1 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
1.1%
1/91 • Number of events 1 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
|
Blood and lymphatic system disorders
Haematological
|
0.55%
1/181 • Number of events 1 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
0.00%
0/182 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
0.00%
0/91 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
1.1%
1/91 • Number of events 1 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
|
Metabolism and nutrition disorders
Metabolic/Endocrine
|
0.00%
0/181 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
0.00%
0/182 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
0.00%
0/91 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
0.00%
0/91 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal
|
0.55%
1/181 • Number of events 1 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
0.55%
1/182 • Number of events 1 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
0.00%
0/91 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
0.00%
0/91 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
|
Infections and infestations
Infection/sepsis
|
1.1%
2/181 • Number of events 2 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
2.2%
4/182 • Number of events 4 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
2.2%
2/91 • Number of events 2 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
1.1%
1/91 • Number of events 1 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour/ malignancy
|
0.55%
1/181 • Number of events 1 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
2.2%
4/182 • Number of events 4 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
1.1%
1/91 • Number of events 1 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
1.1%
1/91 • Number of events 1 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
|
General disorders
Other
|
2.8%
5/181 • Number of events 5 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
3.3%
6/182 • Number of events 6 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
3.3%
3/91 • Number of events 3 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
4.4%
4/91 • Number of events 4 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
|
Cardiac disorders
Cardiovascular
|
2.8%
5/181 • Number of events 5 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
3.8%
7/182 • Number of events 7 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
4.4%
4/91 • Number of events 4 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
2.2%
2/91 • Number of events 2 • From randomisation to 12 months.
Other \[Not Including Serious\] Adverse Events were not monitored/assessed. These are reported as 0 in the table below.
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place