Clinical trial • Phase III • Cardiology
dipyridamole; acetylsalicylic acid (ASA) for Unruptured intracranial saccular aneurysm
Phase III trial of dipyridamole; acetylsalicylic acid (ASA) for Unruptured intracranial saccular aneurysm.
Overview
- Trial Therapeutic Area
- Cardiology
- Trial Disease
- Unruptured intracranial saccular aneurysm
- Trial Stage
- Phase III
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 15-10-2024
- First CTIS Authorization Date
- 22-11-2024
Trial design
Randomised, open-label, intervention: low-dose acetylsalicylic acid (asa) 81-100 mg/day plus intensive blood pressure treatment (target systolic bp <120 mmhg) with weekly home bp measurements. comparator/standard care: no asa and blood pressure management according to standard guidelines (usually treating systolic bp >140 mmhg) with no home weekly bp device.-controlled Phase III trial across 20 sites in Finland, Netherlands, Germany.
- Randomised
- Yes
- Open Label
- Yes
- Comparator
- Intervention: low-dose acetylsalicylic acid (ASA) 81-100 mg/day plus intensive blood pressure treatment (target systolic BP <120 mmHg) with weekly home BP measurements. Comparator/standard care: no ASA and blood pressure management according to standard guidelines (usually treating systolic BP >140 mmHg) with no home weekly BP device.
- Target Sample Size
- 746
- Trial Duration For Participant
- 1095
Eligibility
Recruits 746 Vulnerable population flag is selected. Eligibility requires the subject's ability to understand the character and individual consequences of the clinical trial, the subject must not be legally incapacitated, and written informed consent must be available before enrolment. Subject information/consent documents provided are for adults; no assent or under-18 consent procedures are described..
- Pregnancy Exclusion
- Pregnancy and lactation
- Vulnerable Population
- Vulnerable population flag is selected. Eligibility requires the subject's ability to understand the character and individual consequences of the clinical trial, the subject must not be legally incapacitated, and written informed consent must be available before enrolment. Subject information/consent documents provided are for adults; no assent or under-18 consent procedures are described.
Inclusion criteria
- {"criterion_text":"- 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\n- 18 years or older\n- Last aneurysm imaging with either CTA/MRA within the last 3 months\n- Ability of subject to understand character and individual consequences of clinical trial\n- Not legally incapacitated\n- Written informed consent (must be available before enrolment in the trial)\n- For women with childbearing potential adequate contraception."}
Exclusion criteria
- {"criterion_text":"- All non-saccular UIAs or aneurysms related to arteriovenous malformations\n- Participation in another interventional clinical trial\n- Life-expectancy <3 years\n- Daily ASA already prescribed for another indication\n- Use of a vitamin K antagonist or direct oral anticoagulant (DOAC) treatment at baseline\n- 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\n- History of asthma induced by salicylates or other anti-inflammatory drugs\n- 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)\n- Use of another platelet aggregation inhibitor, which in combination with ASA would give an unacceptable risk of side effects/complications\n- Chronic kidney disease stage IV and V (GFR <30mL/min/1.73m2)\n- Pregnancy and lactation"}
Endpoints
Primary endpoints
- {"endpoint_text":"- 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.","definition_or_measurement_approach":"Aneurysm growth is defined in the primary endpoint text: \"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.\" Assessment is by serial MR- or CT-angiography and independent blinded radiologists; suspicious events are centrally adjudicated."}
Secondary endpoints
- {"endpoint_text":"- Definite aSAH, probable aSAH, or aneurysm growth irrespective of the time since randomization","definition_or_measurement_approach":""}
- {"endpoint_text":"- Definite aSAH, probable aSAH, possible aSAH, or aneurysm growth irrespective of the time since randomization","definition_or_measurement_approach":""}
- {"endpoint_text":"- Increase of aneurysm volume in computerized measurements from source images by >10% and >3mm3 or appearance of daughter sac","definition_or_measurement_approach":"Measurement by computerized volume measurements from source images; threshold defined as >10% and >3 mm3 increase or appearance of a daughter sac."}
- {"endpoint_text":"- Development of de novo aneurysm on serial imaging","definition_or_measurement_approach":""}
- {"endpoint_text":"- Neurosurgical/endovascular treatment of the UIA during the study period","definition_or_measurement_approach":""}
- {"endpoint_text":"- Any ischemic or hemorrhagic stroke, defined as clinical symptoms of stroke AND a compatible lesion on imaging (either plain head CT/CT perfusion/MRI)","definition_or_measurement_approach":"Defined as clinical symptoms of stroke AND a compatible lesion on imaging (plain head CT/CT perfusion/MRI)."}
- {"endpoint_text":"- Myocardial infarction defined as increase of Troponin, CK-MB and/or presence of new significant Q waves obtained on ECG","definition_or_measurement_approach":"Defined by increase of Troponin, CK-MB and/or presence of new significant Q waves on ECG."}
- {"endpoint_text":"- Vascular death (including fatal stroke, fatal myocardial infarction, sudden death)","definition_or_measurement_approach":""}
- {"endpoint_text":"- Major spontaneous bleeding, defined as bleeding requiring hospitalization or leading to death or disability (including definite and probable aSAH","definition_or_measurement_approach":"Defined as bleeding requiring hospitalization or leading to death or disability (including definite and probable aSAH)."}
- {"endpoint_text":"- Blood pressure (as measured during follow-up visits)","definition_or_measurement_approach":"Measured during follow-up visits."}
- {"endpoint_text":"- Safety aspects (adverse and serious adverse events, including those mentioned above, see also 8.1.6 and 8.2)","definition_or_measurement_approach":"Adverse and serious adverse events monitoring as per protocol sections referenced."}
- {"endpoint_text":"- Quality of life (as determined by completion of the paper-based EQ-5D-5L form by patient)","definition_or_measurement_approach":"Assessed by patient completion of the paper-based EQ-5D-5L form."}
Recruitment
- Planned Sample Size
- 746
- Recruitment Window Months
- 140
- Consent Approach
- Written informed consent from the adult participant is required prior to enrolment; subjects must be able to understand the trial and not be legally incapacitated. Consent documents for adults are provided (documents in Finnish, Dutch and German are listed in the dossier). No assent procedures for minors are described.
Geography
- Total Number Of Sites
- 20
- Total Number Of Participants
- 746
Finland
- Earliest CTIS Part Ii Submission Date
- 25-10-2024
- Latest Decision Or Authorization Date
- 10-03-2026
- Processing Time Days
- 501
- Number Of Sites
- 5
- Number Of Participants
- 120
Sites
- Site Name
- Tampere University Hospital
- Department Name
- Neurosurgery
- Principal Investigator Name
- Juhana Frösen
- Principal Investigator Email
- Juhana.Frosen@pirha.fi
- Contact Person Name
- Juhana Frösen
- Contact Person Email
- Juhana.Frosen@pirha.fi
- Site Name
- Oulu University Hospital
- Department Name
- Neurosurgery
- Principal Investigator Name
- Sami Tetri
- Principal Investigator Email
- sami.tetri@ppshp.fi
- Contact Person Name
- Sami Tetri
- Contact Person Email
- sami.tetri@ppshp.fi
- Site Name
- HUS-Yhtymae
- Department Name
- Neurosurgery
- Principal Investigator Name
- Ville Nurminen
- Principal Investigator Email
- ville.nurminen@hus.fi
- Contact Person Name
- Ville Nurminen
- Contact Person Email
- ville.nurminen@hus.fi
- Site Name
- Turku University Hospital
- Department Name
- Neurosurgery
- Principal Investigator Name
- Jaakko Rinne
- Principal Investigator Email
- jaakko.rinne@utu.fi
- Contact Person Name
- Jaakko Rinne
- Contact Person Email
- jaakko.rinne@utu.fi
- Site Name
- Kuopio University Hospital
- Department Name
- Neurosurgery
- Principal Investigator Name
- Timo Koivisto
- Principal Investigator Email
- FINNHEALTH@KUH.FI
- Contact Person Name
- Timo Koivisto
- Contact Person Email
- FINNHEALTH@KUH.FI
Netherlands
- Earliest CTIS Part Ii Submission Date
- 25-10-2024
- Latest Decision Or Authorization Date
- 11-03-2026
- Processing Time Days
- 502
- Number Of Sites
- 7
- Number Of Participants
- 226
Sites
- Site Name
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Department Name
- Neurology
- Principal Investigator Name
- Bob Roozenbeek
- Principal Investigator Email
- b.roozenbeek@erasmusmc.nl
- Contact Person Name
- Bob Roozenbeek
- Contact Person Email
- b.roozenbeek@erasmusmc.nl
- Site Name
- Universitair Medisch Centrum Groningen
- Department Name
- Neurology
- Principal Investigator Name
- Maarten Uyttenbooga
- Principal Investigator Email
- m.uyttenboogaart@umcg.nl
- Contact Person Name
- Maarten Uyttenbooga
- Contact Person Email
- m.uyttenboogaart@umcg.nl
- Site Name
- Radboud universitair medisch centrum Stichting
- Department Name
- Neurosurgery
- Principal Investigator Name
- Jeroen Boogaarts
- Principal Investigator Email
- Jeroen.Boogaarts@radboudumc.nl
- Contact Person Name
- Jeroen Boogaarts
- Contact Person Email
- Jeroen.Boogaarts@radboudumc.nl
- Site Name
- Stichting Elisabeth-Tweesteden Ziekenhuis
- Department Name
- Neurosurgery
- Principal Investigator Name
- Bram van der Pol
- Principal Investigator Email
- bram.vanderpol@etz.nl
- Contact Person Name
- Bram van der Pol
- Contact Person Email
- bram.vanderpol@etz.nl
- Site Name
- Academisch Medisch Centrum
- Department Name
- Neurosurgery
- Principal Investigator Name
- Dagmar Verbaan
- Principal Investigator Email
- d.verbaan@amsterdamumc.nl
- Contact Person Name
- Dagmar Verbaan
- Contact Person Email
- d.verbaan@amsterdamumc.nl
- Site Name
- Universitair Medisch Centrum Utrecht
- Department Name
- Neurosurgery
- Principal Investigator Name
- Mervyn Vergouwen
- Principal Investigator Email
- M.D.I.Vergouwen@umcutrecht.nl
- Contact Person Name
- Mervyn Vergouwen
- Contact Person Email
- M.D.I.Vergouwen@umcutrecht.nl
- Site Name
- Haaglanden Medisch Centrum Stichting
- Department Name
- Neurology
- Principal Investigator Name
- Ido van den Wijngaard
- Principal Investigator Email
- i.van.den.wijngaard@haaglandenmc.nl
- Contact Person Name
- Ido van den Wijngaard
- Contact Person Email
- i.van.den.wijngaard@haaglandenmc.nl
Germany
- Earliest CTIS Part Ii Submission Date
- 25-10-2024
- Latest Decision Or Authorization Date
- 09-03-2026
- Processing Time Days
- 500
- Number Of Sites
- 8
- Number Of Participants
- 400
Sites
- Site Name
- Heidelberg University
- Department Name
- Neurochirurgische Klinik
- Principal Investigator Name
- Nima Etminan
- Principal Investigator Email
- nima.etminan@umm.de
- Contact Person Name
- Nima Etminan
- Contact Person Email
- nima.etminan@umm.de
- Site Name
- Universitaetsklinikum Aachen AöR
- Department Name
- Neurochirurgische Klinik
- Principal Investigator Name
- Anke Höllig
- Principal Investigator Email
- ahoellig@ukaachen.de
- Contact Person Name
- Anke Höllig
- Contact Person Email
- ahoellig@ukaachen.de
- Site Name
- Universitaetsmedizin Goettingen
- Department Name
- Neurochirurgische Klinik
- Principal Investigator Name
- Veit Rohde
- Principal Investigator Email
- veit.rohde@med.uni-goettingen.de
- Contact Person Name
- Veit Rohde
- Contact Person Email
- veit.rohde@med.uni-goettingen.de
- Site Name
- Medical Center - University Of Freiburg
- Department Name
- Neurochirurgische Klinik
- Principal Investigator Name
- Roland Rölz
- Principal Investigator Email
- roland.roelz@uniklinik-freiburg.de
- Contact Person Name
- Roland Rölz
- Contact Person Email
- roland.roelz@uniklinik-freiburg.de
- Site Name
- Universitaetsklinikum Essen AöR
- Department Name
- Neurochirurgische Klinik
- Principal Investigator Name
- Ramazan Jabbarli
- Principal Investigator Email
- Ramazan.Jabbarli@uk-essen.de
- Contact Person Name
- Ramazan Jabbarli
- Contact Person Email
- Ramazan.Jabbarli@uk-essen.de
- Site Name
- Charite Universitaetsmedizin Berlin KöR
- Department Name
- Neurochirurgische Klinik
- Principal Investigator Name
- Peter Vaikoczy
- Principal Investigator Email
- peter.vajkoczy@charite.de
- Contact Person Name
- Peter Vaikoczy
- Contact Person Email
- peter.vajkoczy@charite.de
- Site Name
- Universitaetsklinikum Duesseldorf AöR
- Department Name
- Neurochirurgische Klinik
- Principal Investigator Name
- Sajjad Muhammad
- Principal Investigator Email
- muhammad@uni-duesseldorf.de
- Contact Person Name
- Sajjad Muhammad
- Contact Person Email
- muhammad@uni-duesseldorf.de
- Site Name
- Goethe University Frankfurt
- Department Name
- Klinik für Neurologie und Neurochirurgie
- Principal Investigator Name
- Jan Hendrik Schäfer
- Principal Investigator Email
- janhendrik.schaefer@unimedizin-ffm.de
- Contact Person Name
- Jan Hendrik Schäfer
- Contact Person Email
- janhendrik.schaefer@unimedizin-ffm.de
Sponsor
Primary sponsor
- Full Name
- Heidelberg University
- Organisation Type
- Educational Institution
- Country Of Registered Address
- Germany
Third parties
- {"country":"Germany","full_name":"Universitaetsklinikum Heidelberg AöR","duties_or_roles":"codes: 1,12,5,6,8","organisation_type":"Hospital/Clinic/Other health care facility"}
Investigational products
- Investigational Product Name
- ACETYLSALICYLIC ACID
- Active Substance
- dipyridamole; acetylsalicylic acid (ASA)
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- ORAL
- Starting Dose
- 81-100 mg/day
- Frequency
- daily
- Maximum Dose
- 100 mg/day
- Combination Treatment
- Yes
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