Use of statins in patients with intracerebral hemorrhage

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacio Institut De Recerca De L Hospital De La Santa Creu I Sant Pau

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02], Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Trial duration

20 Nov 2024 → ongoing

Decision date (initial)

2024-11-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-511465-11-00

EudraCT number

2022-002266-33

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

EFFICACY: To determine the effects of continuation vs. discontinuation of statins on the risk of ICH recurrence during 24 months of follow-up in patients presenting with a spontaneous lobar lCH while taking a statin drug. Specifically, we wish to determine the effects of discontinuing vs. continuing statins on the risk of recurrent symptomatic ICH. We hypothesize that discontinuation of statins in patients with lobar ICH is likely associated with reduced risk of ICH recurrence.
SAFETY: To determine the effects of discontinuation vs. continuation of statins on the occurrence of any of the following major adverse cardiac and cerebrovascular events (MACCE): symptomatic ischemic stroke, symptomatic myocardial infarction, newly symptomatic arterial occlusive disease (peripheral, retinal, or carotid), revascularization procedures for coronary, carotid, or peripheral arterial disease, and vascular death. We specifically wish to estimate the relative and absolute effects of discontinuing statins on the risk of these MACCE during the 24 month follow-up period. We hypothesize that discontinuation of statins is likely associated with an increase in the risk of MACCE.

Secondary objectives 2

1. To examine quality of life, functional, and cognitive outcomes in participants in whom statins are continued vs. discontinued, by repeated assessments of the EQ-5D quality of life questionnaire, modified Rankin Scale (mRS), and Telephone Montreal Cognitive Assessment (T-MoCA) at 3, 6, 9, 12, 18, and 24 months. We hypothesize that the likelihood of neurological and functional disability and death are increased with recurrent ICH compared to most MACCE, and that patients who discontinue statins will achieve better outcomes than those who continue statins because of reduced risk of ICH recurrence. These outcomes will be used to aid the assessment of the trade-off between efficacy and safety outcomes stated above
2. To prospectively examine whether the presence vs. absence of APOE ε4 and APOE ε2 genotypes modifies the effects of statins on the risk of recurrent ICH (i.e., whether APOE genotype can be used as a biological marker to stratify the risk of ICH recurrence in statinstreated patients). We hypothesize that patients with lobar ICH and APOE ε4 or APOE ε2 genotypes have an increased risk of recurrent ICH with continuation of statins therapy. If this hypothesis is true, avoiding statins in this subset of lobar ICH patients with these biological markers might be particularly helpful to reduce the risk of ICH recurrence.

Conditions and MedDRA coding

Spontaneous lobar ICH

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age ≥ 50 years.
2. Spontaneous lobar ICH confirmed by CT or MRI scan
3. Patient was taking a statin drug at the onset of the qualifying/index ICH
4. Randomization must be carried out within 7 days of the onset of the qualifying ICH
5. Patient or LAR, after consultation with the physicians prescribing statin, agrees to be randomized to statin continuation (restart) vs. discontinuation

Exclusion criteria 15

1. Suspected secondary cause for the qualifying ICH, such as an underlying vascular abnormality or tumor, trauma, venous infarction, or hemorrhagic transformation of an ischemic infarct.
2. History of recent myocardial infarction (attributed to coronary artery disease) or unstable angina within the previous 3 months
3. Diabetic patients with history of myocardial infarction or coronary revascularization
4. History of familial hypercholesterolemia
5. Patients receiving proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors
6. Known diagnosis of severe dementia
7. Inability to obtain informed consent
8. Patients known or suspected of not being able to comply with the study protocol due to alcoholism, drug dependency, or other obvious reasons for noncompliance, such as unable to adhere to the protocol specified visits/assessments.
9. Life expectancy of less than 24 months due to co-morbid terminal conditions.
10. Pre-morbid mRS >3
11. ICH score >3 upon presentation.
12. Contraindications to continuation/resumption of statin therapy, such as significant elevations of serum creatinine kinase and/or liver transaminases, and rhabdomyolysis
13. Concurrent participation in another research protocol for investigation of experimental therapy
14. Women of childbearing potential
15. Indication that withdrawal of care will be implemented for the qualifying ICH.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The main efficacy endpoint is the impact of continuing vs. discontinuing statins on the risk of recurrent symptomatic intracerebral hemorrhage (ICH) over a 24-month follow-up period. The safety primary endpoint focuses on the occurrence of major adverse cardiac and cerebrovascular events (MACCE), including ischemic stroke, myocardial infarction, and vascular death

Secondary endpoints 1

1. Secondary endpoints include quality of life, cognitive and functional outcomes, measured through the EQ-5D questionnaire, modified Rankin Scale (mRS), and Telephone Montreal Cognitive Assessment (T-MoCA). Additionally, the document examines the effects of APOE ε4 and ε2 genotypes on the risk of recurrent ICH​

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacio Institut De Recerca De L Hospital De La Santa Creu I Sant Pau

Sponsor organisation

Fundacio Institut De Recerca De L Hospital De La Santa Creu I Sant Pau

Address

Calle De San Quintin 77-79

City

Barcelona

Postcode

08041

Country

Spain

Scientific contact point

Organisation

Fundacio Institut De Recerca De L Hospital De La Santa Creu I Sant Pau

Contact name

Alejandra Espinosa

Public contact point

Organisation

Fundacio Institut De Recerca De L Hospital De La Santa Creu I Sant Pau

Contact name

Alejandra Espinosa

Locations

1 EU/EEA country · 30 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications