This study has been transitioned to CTIS with ID 2024-517236-22-00 check the CTIS register for the current data. The main purpose of this study is to assess the hypothesis that a strategy with ASA 100mg/day and intensive blood pressure treatment (…
ID
Source
Brief title
Condition
- Aneurysms and artery dissections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome measure will be aneurysm rupture or growth on serial
imaging (MR- or CT-angiography). Aneurysm growth is defined as an increase in
any aneurysm diameter by >= 1mm at 36±6 months on the intervention. Aneurysm
rupture or growth will be assessed centrally by two independent trial
radiologists, who will be blinded to the treatment allocation.
Secondary outcome
1. Any growth or rupture of aneurysm during follow-up irrespective of the
duration of trial participation
2. Difference of aneurysm volume (defined as increase of aneurysm volume in
computerized measurements from source images by >10% and >3mm3) or aneurysm
shape (e.g. development of daughter sac)
3. Development of de novo aneurysm on serial imaging
4. Clipping/coiling during the study period
5. Any ischemic or hemorrhagic stroke, defined as clinical symptoms of stroke
AND a compatible lesion on imaging
6. Myocardial infarction defined as increase of Troponin, CKMB and/or presence
of new significant Q waves obtained in ECG
7. Vascular death (including fatal stroke, fatal myocardial infarction, sudden
death)
8. Death from all other causes
9. Major spontaneous bleeding requiring hospitalisation defined as
substantially disabling bleeding, intraocular bleeding leading to the loss of
vision, or bleeding necessitating the transfusion of at least 2 units of
erythrocyte concentrates
10. Blood pressure; any data on blood pressure management used
11. Safety aspects (adverse and serious adverse events)
12. Quality of life
Background summary
In the Netherlands, approximately 300.000 people have an intracranial aneurysm.
Most people are not aware of having an intracranial aneurysm until brain
imaging is made for another reason, such as traumatic head injury. An
intracranial aneurysm can then be found by accident. If such an aneurysm is
found, it needs to be considered if preventive aneurysm treatment should occur
to prevent bleeding. Preventive aneurysm treatment can be done by neurosurgical
clipping or endovascular coiling. However, both treatment options have a risk
of treatment complications, such as ischemic or hemorrhagic stroke. It will
only be decided to do preventive aneurysm treatment if the risk of aneurysm
rupture is larger than the risk of treatment complications. Because most
aneurysm are relatively small and have a low risk of rupture, most aneurysms
remain untreated. Patients with such an aneurysm receive a 'wait-and- scan'
policy to determine if the aneurysm growths. Aneurysm growth increases the risk
of rupture, and therefore in these patients it can be decided in a later phase
to perform preventive aneurysm treatment.
In the PROTECT-U trial, we focus on patients in whom the risk of aneurysm
rupture is lower than the risk of treatment complications: the untreated group
of patients. Previous studies suggested that acetylsalicyl acid decreases
inflammation in the aneurysm wall and hereby the risk of aneurysm rupture. In
addition, high blood pressure is a risk factor for aneurysm rupture. In the
PROTECT-U trial we will randomize 776 patient to either treatment with daily
acetylsalicylic acid and intensive blood pressure treatment in combination with
weakly home blood pressure measurements OR current standard of care (this is
the control group, there is no need to take a placebo).
Study objective
This study has been transitioned to CTIS with ID 2024-517236-22-00 check the CTIS register for the current data.
The main purpose of this study is to assess the hypothesis that a strategy with
ASA 100mg/day and intensive blood pressure treatment (targeted systolic blood
pressure below 120mmHg) with advice to patients to do weekly measurements using
a home blood pressure measuring device reduces the risk of aneurysm growth or
rupture compared with standard care (i.e. no ASA, blood pressure management
according to guidelines which advise treatment if systolic blood pressure
exceeds 140mmHg, and no home device for weekly blood pressure measuring).
Study design
International, phase III multicenter, randomised, controlled trial with a PROBE
design (prospective, randomised, open-label trial with blinded outcome
assessment)
Intervention
Patients will be randomized to either:
- a strategy with ASA 100mg/day and intensive blood pressure treatment
(targeted systolic blood pressure below 120 mm Hg) with daily measurements
using a home blood pressure measuring device
- standard care (i.e. no ASA, blood pressure management according to guidelines
which usually advise treatment if systolic blood pressure exceeds 140 mm Hg,
and no home device for daily blood pressure measurements).
Blood pressure lowering drugs will not be part of the IMP. Both in the
intervention arm and the control arm of the trial, the general practitioner
will control the blood pressure target and prescribe blood pressure lowering
drugs (but with different targets of systolic blood pressures in the two arms).
Study burden and risks
If a recent (<6 months) GFR (determined at the lab of the trial center or at
another lab that provides a copy of the appropriate lab certificate) is not
available, a blood test will be done to measure GFR after informed consent has
been obtained. In women with child-bearing potential, a pregnancy test will be
done.
The patients included in this study will be randomly assigned to either
acetylsalicylic acid 100 mg once daily in combination with intensive blood
pressure treatment (target systolic BP <120 mm Hg) and a home blood pressure
measuring device in addition to standard of care or only standard clinical
care. Side effects of acetylsalicylic acid may include nausea, vomiting,
dyspepsia, stomach ache, and a gastrointestinal bleeding tendency.
All patients will have a treatment visit every 6 months during which a blood
pressure, potential side effects, cardiovascular outcomes, hospital admissions,
and quality of life are recorded. There is no risk related to these treatment
visits. Treatment visits will take place until the study is finished, 3 years
after inclusion of the last patient. Therefore, the patient will be in the
trial for 3-5 years, depending on the time of inclusion. There will be a
minimum of 9 visits, and a maximum of 13 visits (including the screening-,
baseline- and follow-up visits).
Aneurysm imaging is part of patient care, and therefore is no study procedure.
Patients of the treatment group, who consent into an additional data upload,
are instructed how to transmit pseudonymised blood pressure measurements into a
central database by online transfer.
Seminarstraße 2 2
Heidelberg D-69117
DE
Seminarstraße 2 2
Heidelberg D-69117
DE
Listed location countries
Age
Inclusion criteria
• 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
• 18 years or older
• Last aneurysm imaging with either CTA/MRA within the last 3 months
• Ability of subject to understand character and individual consequences of
clinical trial
• Not legally incapacitated
• Written informed consent (must be available before enrolment in the trial)
• For women with childbearing potential adequate contraception
Exclusion criteria
• All non-saccular UIAs or aneurysms related to arteriovenous malformations • Daily ASA already prescribed for another indication • Use of a vitamin K antagonist or direct oral anticoagulant (DOAC) at baseline • History of hypersensitivity to ASA or to any other drug with similar chemical structure or to any excipient present in the pharmaceutical form of ASA • History of asthma induced by ASA or other anti-inflammatory drugs • Other contra-indications for ASA not yet mentioned, in the dosage of 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) • Use of another platelet aggregation inhibitor, which in combination with ASA would give an unacceptable risk of side effects/complications • Chronic kidney disease stage IV and V (GFR < 30 mL/min/1.73 m2) • Pregnancy and lactation • Participation in any other clinical trial • Life-expectancy <3 years
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-517236-22-00 |
| EudraCT | EUCTR2017-000514-35-NL |
| ClinicalTrials.gov | NCT03063541 |
| CCMO | NL63115.041.17 |