Acetylsalicylic Acid Plus Intensive Blood Pressure Treatment in Patients With Unruptured Intracranial Aneurysms (PROTECT-U)
Primary Purpose
Unruptured Intracranial Aneurysms
Status
Unknown status
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Acetylsalicylic acid
intensive blood pressure control
Sponsored by
About this trial
This is an interventional prevention trial for Unruptured Intracranial Aneurysms
Eligibility Criteria
Inclusion Criteria:
- Patients 18 years or older with an intradural, saccular unruptured aneurysm (UIA) in whom it is decided not to intervene with preventive endovascular or neurosurgical repair of the aneurysm and who are monitored on a regular base for aneurysm growth
- Last aneurysm imaging with either CTA/MRA/DSA within the last 3 months
Exclusion Criteria:
- All non-saccular UIAs or aneurysms related to arteriovenous malformations
- Frequent ASA use and/or indication for a vitamin K antagonist, or direct oral anticoagulant (DOAC) treatment at baseline
- Contra-indication for ASA
- 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
- Chronic kidney disease stage IV and V (GFR < 30 mL/min/1.73 m2)
- Pregnancy and lactation
- Participation in another clinical trial or observation period of competing trials, respectively
- Life-expectancy <3 years
Sites / Locations
- Department of Neurology and Neurosurgery, Goethe UniversityRecruiting
- Klinik für NeurochirurgieRecruiting
- Neurochirurgische KlinikRecruiting
- Neurochirurgische KlinikRecruiting
- Neurolgische KlinikRecruiting
- Klinik für NeurochirurgieRecruiting
- Klinik für NeurochirurgieRecruiting
- Klinik für NeurochirurgieRecruiting
- Neurologische UniversitätsklinikRecruiting
- Department of Neurosurgery, University Hospital MannheimRecruiting
- Neurochirurgische Klinik und Poliklinik
- Universitätsklinikum MünsterRecruiting
- AMC Department of NeurologyRecruiting
- UMCGRecruiting
- Leiden University Medical CenterRecruiting
- Neurochirurgisch Centrum CWZRecruiting
- Erasmus MCRecruiting
- UMCRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Acetylsalicylic acid, BP-target 120
standard care
Arm Description
100 mg ASA plus intensified blood pressure management. Recommended systolic blood pressure 120 mm/Hg
blood pressure management according to guidelines
Outcomes
Primary Outcome Measures
aneurysm rupture or growth
aneurysm rupture (i.e. aneurysmal subarachnoid hemorrhage, SAH) or growth (increase in any aneurysm diameter by ≥1mm) on serial imaging (either two MR or CT angiographies)
Secondary Outcome Measures
aneurysm volume
difference of aneurysm volume (in computerized measurements defined as increase of aneurysm volume in computerized measurements by >10% and >3mm3 or aneurysm shape (e.g. development of daughter sac)
new aneurysm
development of de novo aneurysm on serial imaging
therapy of aneurysm
clipping/coiling during the study period
stroke
any ischemic or haemorrhagic stroke, defined as clinical symptoms for stroke AND a compatible lesion on imaging
myocard infarction
myocardial infarction defined as increase of troponin, creatine-kinase MB and/or presence of new significant Q waves obtained in electrocardiography
vascular death
vascular death (including fatal stroke, fatal myocardial infarction, sudden death)
major bleeding
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
death
death from all other causes
achieved blood pressure
any data on blood pressure management used
Incidence of Treatment-Emergent Adverse and Serious Adverse Events
all adverse and serious adverse events related to the experimental intervention
Full Information
NCT ID
NCT03063541
First Posted
February 20, 2017
Last Updated
January 23, 2019
Sponsor
Universitätsmedizin Mannheim
Collaborators
UMC Utrecht, Schwiete Stiftung, Mannheim, Germany, KKS Netzwerk, University of Hamburg-Eppendorf
1. Study Identification
Unique Protocol Identification Number
NCT03063541
Brief Title
Acetylsalicylic Acid Plus Intensive Blood Pressure Treatment in Patients With Unruptured Intracranial Aneurysms
Acronym
PROTECT-U
Official Title
Prospective Randomized Open-label Trial to Evaluate Risk faCTor Management in Patients With Unruptured Intracranial Aneurysms
Study Type
Interventional
2. Study Status
Record Verification Date
January 2019
Overall Recruitment Status
Unknown status
Study Start Date
September 21, 2017 (Actual)
Primary Completion Date
October 2022 (Anticipated)
Study Completion Date
October 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Universitätsmedizin Mannheim
Collaborators
UMC Utrecht, Schwiete Stiftung, Mannheim, Germany, KKS Netzwerk, University of Hamburg-Eppendorf
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Purpose of this study is to assess the hypothesis that a strategy with acetylsalicylic acid (ASA) 100 mg/day, intensive blood pressure treatment (targeted systolic blood pressure below 120 mmHg), and a 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 standard blood pressure management, no blood pressure measuring device)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Unruptured Intracranial Aneurysms
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
controlled open trial, randomized 1:1
Masking
Outcomes Assessor
Masking Description
observer blinding
Allocation
Randomized
Enrollment
776 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Acetylsalicylic acid, BP-target 120
Arm Type
Experimental
Arm Description
100 mg ASA plus intensified blood pressure management. Recommended systolic blood pressure 120 mm/Hg
Arm Title
standard care
Arm Type
No Intervention
Arm Description
blood pressure management according to guidelines
Intervention Type
Drug
Intervention Name(s)
Acetylsalicylic acid
Other Intervention Name(s)
aspirin
Intervention Description
100 mg daily as one tablet
Intervention Type
Other
Intervention Name(s)
intensive blood pressure control
Intervention Description
Patients are encouraged to seek any therapy to have a systolic blood pressure of 120 or below. They will be provided with a blood pressure measurement device and are advised to control blood pressure daily.
Primary Outcome Measure Information:
Title
aneurysm rupture or growth
Description
aneurysm rupture (i.e. aneurysmal subarachnoid hemorrhage, SAH) or growth (increase in any aneurysm diameter by ≥1mm) on serial imaging (either two MR or CT angiographies)
Time Frame
36 months
Secondary Outcome Measure Information:
Title
aneurysm volume
Description
difference of aneurysm volume (in computerized measurements defined as increase of aneurysm volume in computerized measurements by >10% and >3mm3 or aneurysm shape (e.g. development of daughter sac)
Time Frame
36 months
Title
new aneurysm
Description
development of de novo aneurysm on serial imaging
Time Frame
36 months
Title
therapy of aneurysm
Description
clipping/coiling during the study period
Time Frame
36 months
Title
stroke
Description
any ischemic or haemorrhagic stroke, defined as clinical symptoms for stroke AND a compatible lesion on imaging
Time Frame
36 months
Title
myocard infarction
Description
myocardial infarction defined as increase of troponin, creatine-kinase MB and/or presence of new significant Q waves obtained in electrocardiography
Time Frame
36 months
Title
vascular death
Description
vascular death (including fatal stroke, fatal myocardial infarction, sudden death)
Time Frame
36 months
Title
major bleeding
Description
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
Time Frame
36 months
Title
death
Description
death from all other causes
Time Frame
36 months
Title
achieved blood pressure
Description
any data on blood pressure management used
Time Frame
36 months
Title
Incidence of Treatment-Emergent Adverse and Serious Adverse Events
Description
all adverse and serious adverse events related to the experimental intervention
Time Frame
36 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients 18 years or older with an intradural, saccular unruptured aneurysm (UIA) in whom it is decided not to intervene with preventive endovascular or neurosurgical repair of the aneurysm and who are monitored on a regular base for aneurysm growth
Last aneurysm imaging with either CTA/MRA/DSA within the last 3 months
Exclusion Criteria:
All non-saccular UIAs or aneurysms related to arteriovenous malformations
Frequent ASA use and/or indication for a vitamin K antagonist, or direct oral anticoagulant (DOAC) treatment at baseline
Contra-indication for ASA
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
Chronic kidney disease stage IV and V (GFR < 30 mL/min/1.73 m2)
Pregnancy and lactation
Participation in another clinical trial or observation period of competing trials, respectively
Life-expectancy <3 years
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nima Etminan, PD Dr. med.
Phone
+49 621 383-2360
Email
Nima.Etminan@umm.de
First Name & Middle Initial & Last Name or Official Title & Degree
Mervyn DI Vergouwen, M.D., Ph.D.
Phone
+31 88 75 50455
Email
M.D.I.Vergouwen@umcutrecht.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nima Etminan, PD Dr.
Organizational Affiliation
UMM, Department of Neurosurgery
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mervyn D Vergouwen, MD,PhD
Organizational Affiliation
UMC Utrecht, Department of Neurology and Neurosurgery
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Neurology and Neurosurgery, Goethe University
City
Frankfurt am Main
State/Province
Hessen
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Helmuth Steinmetz, Prof. Dr.
Phone
+49 69 6301-5769
Email
helmuth.steinmetz@em.uni-frankfurt.de
First Name & Middle Initial & Last Name & Degree
Jürgen Konczalla, PD Dr
Email
J.Konczalla@med.uni-frankfurt.de
First Name & Middle Initial & Last Name & Degree
Helmuth Steinmetz, Prof. Dr.
Facility Name
Klinik für Neurochirurgie
City
Aachen
ZIP/Postal Code
52074
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gerrit A Schubert, Prof. Dr.
Phone
+49 241 8082420
Email
gschubert@ukaachen.de
First Name & Middle Initial & Last Name & Degree
Rastislav Pjontek, Dr.
Email
rpjontek@ukaachen.de
First Name & Middle Initial & Last Name & Degree
Gerrit A Schubert, Prof. Dr.
Facility Name
Neurochirurgische Klinik
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter Vajkoczy, Prof. Dr.
Phone
+49 30 450 560900
Email
peter.vajkoczy@charite.de
First Name & Middle Initial & Last Name & Degree
Lars Wessels, Dr.
Phone
030 450 56
Ext
0002
Email
lars.wessels@charite.de
First Name & Middle Initial & Last Name & Degree
Peter Vajkoczy, Prof. Dr.
Facility Name
Neurochirurgische Klinik
City
Düsseldorf
ZIP/Postal Code
40225
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Athanasios Petridis, Prof. Dr.
Phone
+49 211810
Ext
4514
Email
athanasios.petridis@duesseldorf.de
First Name & Middle Initial & Last Name & Degree
Kerim Beseoglu, Dr.
Facility Name
Neurolgische Klinik
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hagen Huttner, Prof. Dr.
Phone
+4991318536597
Email
hagen.huttner@uk-erlangen.de
First Name & Middle Initial & Last Name & Degree
Bernd Kallmünzer, Dr.
Email
bernd.kallmuenzer@uk-erlangen.de
First Name & Middle Initial & Last Name & Degree
Hagen Huttner, Prof. Dr.
Facility Name
Klinik für Neurochirurgie
City
Essen
ZIP/Postal Code
45147
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ramazan Jabbarli, PD Dr.
Email
ramazan.jabbarli@uk-essen.de
First Name & Middle Initial & Last Name & Degree
Ramazan Jabbarli, PhD
Facility Name
Klinik für Neurochirurgie
City
Göttingen
ZIP/Postal Code
37037
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dorothe Mielke, Prof. Dr.
Email
dorothe.mielke@med.uni-goettingen.de
First Name & Middle Initial & Last Name & Degree
Katharina Lange
Email
katharina.lange@med.uni-goettingen.de
First Name & Middle Initial & Last Name & Degree
Veit Rohde, Prof. Dr.
Facility Name
Klinik für Neurochirurgie
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nils O Schmidt, PD Dr.
Email
nschmidt@uke.de
First Name & Middle Initial & Last Name & Degree
Jan Regelsberger, Prof. Dr.
Email
j.regelsberger@uke.de
First Name & Middle Initial & Last Name & Degree
Nils O Schmidt, PD Dr.
Facility Name
Neurologische Universitätsklinik
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter A Ringleb, Prof. Dr.
Phone
+496221 56-
Ext
8243
First Name & Middle Initial & Last Name & Degree
Elisabeth Beyrle
Phone
+406221 563-
Ext
8856
Email
elisabeth.beyrle@med.uni-heidelberg.de
First Name & Middle Initial & Last Name & Degree
Peter A Ringleb, Prof. Dr.
Facility Name
Department of Neurosurgery, University Hospital Mannheim
City
Mannheim
ZIP/Postal Code
68167
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nima Etminan, PD Dr. med.
Phone
+49-621-383-2360
Email
nima.etminan@umm.de
First Name & Middle Initial & Last Name & Degree
Katharina Hackenberg, Dr.med.
Phone
+49-621-383-2360
Email
katharina.hackenberg@umm.de
First Name & Middle Initial & Last Name & Degree
Nima Etminan, PD Dr.med.
First Name & Middle Initial & Last Name & Degree
Daniel Haenggi, Prof. Dr.med.
Facility Name
Neurochirurgische Klinik und Poliklinik
City
München
ZIP/Postal Code
81675
Country
Germany
Individual Site Status
Active, not recruiting
Facility Name
Universitätsklinikum Münster
City
Münster
ZIP/Postal Code
48149
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Markus Holling, MD PhD
Phone
+49 251 / 83 -47482
Email
hollingm@ukmuenster.de
First Name & Middle Initial & Last Name & Degree
Markus Holling, MD PhD
Facility Name
AMC Department of Neurology
City
Amsterdam
ZIP/Postal Code
1105AZ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yvo B. W. Roos, Prof. Dr.
Phone
+31-20-5663942
Email
y.b.roos@amc.uva.nl
First Name & Middle Initial & Last Name & Degree
Rita Sprengers
Email
r.g.sprengers@amc.uva.nl
First Name & Middle Initial & Last Name & Degree
Yvo Roos, Prof. Dr.
Facility Name
UMCG
City
Groningen
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maarten Uyttenboogaart, Dr.
Email
m.uyttenboogaart@umcg.nl
First Name & Middle Initial & Last Name & Degree
Maarten Uyttenboogaart, Dr.
Facility Name
Leiden University Medical Center
City
Leiden
ZIP/Postal Code
2300 RC
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ghislaine Holswilder, MD
Email
g.holswilder@lumc.nl
First Name & Middle Initial & Last Name & Degree
A van der Meij, MD
Email
a.van_der_meij@lumc.nl
First Name & Middle Initial & Last Name & Degree
Marieke JH Wermer, MD PhD FESO
Facility Name
Neurochirurgisch Centrum CWZ
City
Nijmegen
ZIP/Postal Code
6500 GS
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jeroen Boogaarts, Dr.
Email
jeroen.boogaarts@radboudumc.nl
First Name & Middle Initial & Last Name & Degree
Viktoria Shimanskaya, Dr
Email
vika.shimanskaya@radboudumc.nl
First Name & Middle Initial & Last Name & Degree
Jeroen Boogarts, Dr.
Facility Name
Erasmus MC
City
Rotterdam
ZIP/Postal Code
3015 GD
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Naziha el Ghannouti
Phone
+31 10 704 38 18
Email
n.elghannouti@erasmusmc.nl
First Name & Middle Initial & Last Name & Degree
Bob Roozenbeek, MD PhD
Facility Name
UMC
City
Utrecht
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mervyn D. I. Vergouwen, Dr.
Phone
+31 (0)88 755 0455
Email
M.D.I.Vergouwen@umcutrecht.nl
First Name & Middle Initial & Last Name & Degree
Jacco M. Westeneng
Email
J.M.Westeneng-4@umcutrecht.nl
First Name & Middle Initial & Last Name & Degree
Mervyn D. I. Vergouwen, Dr.
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
30019634
Citation
Vergouwen MD, Rinkel GJ, Algra A, Fiehler J, Steinmetz H, Vajkoczy P, Rutten FH, Luntz S, Hanggi D, Etminan N. Prospective Randomized Open-label Trial to evaluate risk faCTor management in patients with Unruptured intracranial aneurysms: Study protocol. Int J Stroke. 2018 Dec;13(9):992-998. doi: 10.1177/1747493018790033. Epub 2018 Jul 18.
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Acetylsalicylic Acid Plus Intensive Blood Pressure Treatment in Patients With Unruptured Intracranial Aneurysms
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