Prospective Randomized Open-label Trial to Evaluate risk faCTor management in patients with Unruptured intracranial aneurysms (PROTECT-U)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Heidelberg University

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

20 Sep 2017 → ongoing

Decision date (initial)

2024-11-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Phoenix foundation · Dr. Rolf M. Schwiete Foundation (Mannheim, Germany) · State funding for university-level health research Tampere University Hospital · the Brain Aneurysm Foundation, Medical Faculty Mannheim of the University Heidelberg · Dutch Heart Foundation (Netherlands)

External identifiers

EU CT number

2024-517236-22-00

EudraCT number

2017-000514-35

ClinicalTrials.gov

NCT03063541

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis

The primary aim of this study is to assess the hypothesis that a strategy with low-dose ASA (81-100mg/day) and intensive blood pressure treatment (targeted systolic blood pressure below 120mmHg) with weekly measurements using a home blood pressure measuring device reduces the risk of aneurysm rupture or growth compared with standard care (i.e. no ASA, blood pressure management according to guidelines which usually advise treatment if systolic blood pressure exceeds 140mmHg, and no home device for weekly blood pressure measurements).

Secondary objectives 6

1. A) To assess whether ASA reduces the risk of aneurysm rupture or growth compared with no ASA treatment.
2. B) To assess whether intensive blood pressure lowering therapy reduces the risk of aneurysm rupture or growth compared with no intensive blood pressure lowering therapy.
3. C) To assess whether intensive blood pressure treatment plus ASA reduces the incidence of cardiovascular events compared with standard BP treatment alone.
4. D) To assess whether beneficial effects of the intervention with intensive blood pressure treatment and ASA are not negated by side effects of the intervention.
5. E) To assess the effect of the intervention on quality of life
6. F) To investigate if the intervention is cost-effective

Conditions and MedDRA coding

Intradural saccular unruptured aneurysm

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Patient with at least one intradural, saccular unruptured aneurysm in whom it is decided not to intervene with preventive neurosurgical or endovascular aneurysm repair and who are monitored on a regular basis for aneurysm growth
2. 18 years or older
3. Last aneurysm imaging with either CTA/MRA within the last 3 months
4. Ability of subject to understand character and individual consequences of clinical trial
5. Not legally incapacitated
6. Written informed consent (must be available before enrolment in the trial)
7. For women with childbearing potential adequate contraception.

Exclusion criteria 11

1. All non-saccular UIAs or aneurysms related to arteriovenous malformations
2. Daily ASA already prescribed for another indication
3. Use of a vitamin K antagonist or direct oral anticoagulant (DOAC) treatment at baseline
4. History of hypersensitivity/allergy to ASA or to any other drug with similar chemical structure or to any excipient present in the pharmaceutical form of ASA
5. History of asthma induced by salicylates or other anti-inflammatory drugs
6. Other contra-indications for ASA not yet mentioned in the dosage of 81-100 mg/day (e.g. bleeding disorders, gastric ulcers and/or intestinal ulcers, acute liver failure of kidney failure, severe heart failure, treatment with methotrexate in a dosage 15 mg/week or above)
7. Use of another platelet aggregation inhibitor, which in combination with ASA would give an unacceptable risk of side effects/complications
8. Chronic kidney disease stage IV and V (GFR <30mL/min/1.73m2)
9. Pregnancy and lactation
10. Participation in another interventional clinical trial
11. Life-expectancy <3 years

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary outcome measure will be aneurysm rupture or growth on serial imaging (MR- or CTangiography). Aneurysm growth is defined as an increase in any aneurysm diameter by ≥ 1mm within 36±6 months from randomizantrally by two independent trial radiologists, who will be blinded to the treatment allocation. Events suspicious for SAH but negative CT-imaging will be reviewed centrally by the adjudication committee.

Secondary endpoints 12

1. Definite aSAH, probable aSAH, or aneurysm growth irrespective of the time since randomization
2. Definite aSAH, probable aSAH, possible aSAH, or aneurysm growth irrespective of the time since randomization
3. Increase of aneurysm volume in computerized measurements from source images by >10% and >3mm3 or appearance of daughter sac
4. Development of de novo aneurysm on serial imaging
5. Neurosurgical/endovascular treatment of the UIA during the study period
6. Any ischemic or hemorrhagic stroke, defined as clinical symptoms of stroke AND a compatible lesion on imaging (either plain head CT/CT perfusion/MRI)
7. Myocardial infarction defined as increase of Troponin, CK-MB and/or presence of new significant Q waves obtained on ECG
8. Vascular death (including fatal stroke, fatal myocardial infarction, sudden death)
9. Major spontaneous bleeding, defined as bleeding requiring hospitalization or leading to death or disability (including definite and probable aSAH
10. Blood pressure (as measured during follow-up visits)
11. Safety aspects (adverse and serious adverse events, including those mentioned above, see also 8.1.6 and 8.2)
12. Quality of life (as determined by completion of the paper-based EQ-5D-5L form by patient)

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Heidelberg University

Sponsor organisation

Heidelberg University

Address

Seminarstrasse 2, Altstadt Altstadt

City

Heidelberg

Postcode

69117

Country

Germany

Scientific contact point

Organisation

Heidelberg University

Contact name

Prof. Dr. med. Nima Etminan

Public contact point

Organisation

Heidelberg University

Contact name

Prof. Dr. med. Nima Etminan

Third parties 1

Locations

3 EU/EEA countries · 20 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 14 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