The Canadian UnRuptured Endovascular Versus Surgery Trial (CURES)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2015 by Centre hospitalier de l'Université de Montréal (CHUM)
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
Centre de Recherche du Centre Hospitalier de l'Université de Montréal
University of Alberta
Information provided by (Responsible Party):
Jean Raymond, Centre hospitalier de l'Université de Montréal (CHUM)
ClinicalTrials.gov Identifier:
NCT01139892
First received: June 2, 2010
Last updated: March 3, 2015
Last verified: March 2015
  Purpose

Purpose:

Phase 1: (Pilot Phase)

To compare the treatment efficacy of surgical clipping and endovascular coiling for unruptured intracranial aneurysms.

To obtain better estimates of morbidity and mortality related to a surgical or endovascular treatment strategy at one year within the context of an RCT.

To show that an RCT comparing the morbidity and mortality of a surgical management strategy to an endovascular management strategy is feasible.

Phase 2:

To compare the results of surgical and endovascular management strategies, in terms of:

  1. Overall mortality and morbidity at 1 and 5 years.
  2. The clinical efficacy and safety of a surgical or endovascular management strategy at 1 and 5 years

Hypotheses: Phase 1 Hypotheses:

  1. Surgical clipping of intradural, saccular, unruptured intracranial aneurysms is superior to endovascular management in terms of a lesser number of patients experiencing treatment failure.
  2. An RCT comparing the clinical outcomes of a surgical versus endovascular management strategy is feasible.

Phase 1 Primary End-points:

• Treatment failure, hereby defined as having occurred when either: the intended initial modality (surgical or endovascular) fails to occlude the aneurysm, a "major" (saccular) angiographic aneurysm recurrence is found, or an intracranial hemorrhagic event occurs during the 1-year follow-up period.

Phase 1 Secondary End-points:

  1. Overall morbidity and mortality at one year.
  2. Occurrence of morbidity (mRS >2) or mortality following treatment.
  3. Occurrence of failure of aneurysm occlusion using the initial intended treatment modality.
  4. Occurrence of a "major" (saccular) angiographic aneurysm recurrence.
  5. Occurrence of an intracranial hemorrhage following treatment.
  6. Peri-treatment hospitalization lasting more than 5 days
  7. Discharge following treatment to a location other than home

Treatment:

Trial feasibility, or the capacity for patient recruitment, would require enrollment of at least 8 patients per actively recruiting center per year.

Phase 2 Hypotheses:

It may be too early to explicitly define the primary hypothesis of Phase 2, however, the intent of Phase 2 can be expressed as:

  1. One management strategy is superior to the other in terms of clinical outcome at five years.
  2. One management strategy is superior to the other in terms of clinical efficacy at five years.

Condition Intervention Phase
Intracranial Aneurysms
Procedure: Surgical management
Procedure: Endovascular management
Phase 1
Phase 2

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Canadian Study on the Endovascular Treatment of Unruptured Intracranial Aneurysms Versus Surgical Treatment. A Randomized Comparison of Clinical and Angiographic Results of Intracranial Aneurysms

Resource links provided by NLM:


Further study details as provided by Centre hospitalier de l'Université de Montréal (CHUM):

Primary Outcome Measures:
  • Treatment failure [ Time Frame: One Year ] [ Designated as safety issue: Yes ]
    Defined as having occurred when either: the intended initial modality (surgical or endovascular) fails to occlude the aneurysm, a "major" (saccular) angiographic aneurysm recurrence is found, or an intracranial hemorrhagic event occurs during the 1-year follow-up period.


Secondary Outcome Measures:
  • Morbidity and mortality: 2. Hospitalization >5 days : physician reporting. 3. Discharge other than to home: physician reporting. [ Time Frame: one year ] [ Designated as safety issue: Yes ]
    Overall morbidity and mortality at one year. Morbidity = modified Rankin scale score >2. The Modified Rankin Scale score will be determined by an independent health-care professional, not directly involved in the CURES study, and blinded to treatment allocation.

  • Occurrence of morbidity (mRS >2) or mortality following treatment. [ Time Frame: 6 weeks post-treatment ] [ Designated as safety issue: Yes ]
    Occurrence of morbidity (mRS >2) or mortality following treatment. The Modified Rankin Scale score will be determined by an independent health-care professional, not directly involved in the CURES study, and blinded to treatment allocation.

  • Failure of aneurysm occlusion [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

    Occurrence of failure of aneurysm occlusion using the initial intended treatment modality as determined by the local treating physician. Patients left with clinically concerning aneurysm residuals (in the opinion of the treating physician) after the treatment attempt will count as a failure of the initial treatment.

    In the surgically-treated patients, the surgeon's judgment of whether or not the aneurysm is fully occluded with the clip will be used to determine failure of aneurysm occlusion. Because the primary end-points in Phase 1 is a composite end-point, it does not distinguish between aneurysm remnants found immediately post-treatment (failure to completely occlude the aneurysm) and recurrences (or residuals) found at one-year post-treatment. Even if a surgically-treated aneurysm felt to be completely occluded by the surgeon is in fact inadequately treated, this will be found at the one year follow-up imaging mark, and thus does not constitute a source of bias.


  • Occurrence of a "major" (saccular) angiographic aneurysm recurrence. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Occurrence of a "major" (saccular) angiographic aneurysm recurrence.

  • Occurrence of an intracranial hemorrhage [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Determined using non-invasive angiography (CTA or MRA) performed at 12 +/- 2 months post-treatment, with all images sent to CURES headquarters for Core Lab confirmation. This follow-up imaging is considered to be part of normal follow-up after aneurysm treatment. Although CTA and MRA are known to have different sensitivities in detecting aneurysm remnants, both modalities are equally well-suited to the discovery of what we are looking for: a concerning, saccular aneurysm residual or remnant. Because the definition of "major", "concerning", or "saccular" aneurysm residual or remnant remains subjective, (as does the threshold for re-treatment) local investigators will be requested to record the occurrence of what they consider to be a "major" saccular recurrence, but the final determination of this end-point will be determined by an independent Core Lab.

  • Hospitalization lasting more than 5 days [ Time Frame: 6-weeks post-treatment ] [ Designated as safety issue: Yes ]
    This end-point will be recorded by the local treating physician on discharge.

  • Discharge following treatment to a location other than home [ Time Frame: 6-weeks post-treatment ] [ Designated as safety issue: Yes ]
    This end-point will be recorded by the local treating physician on discharge.


Estimated Enrollment: 260
Study Start Date: June 2010
Estimated Study Completion Date: June 2025
Estimated Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Surgical management
Surgical clipping will be performed within 6 weeks of randomization, according to standards of practice, and under general anaesthesia. Aneurysms thought by the treating physicians to require deliberate permanent proximal vessel occlusion, bypasses, and other flow-redirecting treatments that do not directly clip the aneurysm will not be included.
Procedure: Surgical management
Other Name: Arm 1: clipping
Endovascular management
Endovascular treatment will be performed within 6 weeks of randomization, according to standards of practice, and under general anaesthesia. Details regarding type of coils, use of adjunctive techniques such as balloon-remodeling or stents, as well as post-treatment medical management issues, will be left up to the physician performing the endovascular treatment.
Procedure: Endovascular management
Other Name: Arm 2: coiling

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

primary care clinic

Criteria

Inclusion Criteria:

  • Patients at least 18 years of age with at least 10 years of remaining life expectancy
  • At least one documented, intradural, saccular intracranial aneurysm
  • The patient and aneurysm are considered appropriate for either surgical or endovascular treatment by the treating team
  • Aneurysm size 3-25 mm

Exclusion Criteria:

  • Patients with any intracranial hemorrhage, including SAH, within the previous 30 days
  • Lesion characteristics not readily suitable for either endovascular or surgical treatment, in the opinion of the physician(s) intending to treat the aneurysm
  • Multiple aneurysms, where the treatment plan includes both surgical clipping as well as endovascular coiling
  • Aneurysm anticipated (pre-operatively) to require proximal vessel occlusion, a bypass, or other flow-redirecting therapy (such as flow-diverting stents) as part of treatment plan
  • Patients with baseline mRS >2
  • Patients with a single cavernous aneurysm
  • Patients with dissecting, fusiform, or mycotic aneurysms
  • Patients with AVM-associated aneurysms
  • Pregnant patients (randomization (and treatment) may be delayed until after delivery)
  • Patients with absolute contraindications to anaesthesia, endovascular treatment or administration of contrast material, including low-osmolarity agents or gadolinium
  • Patients unable to give informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01139892

Contacts
Contact: Jean Raymond, MD 514-890-8000 ext 27235 jraymond.nri@gmail.com
Contact: Suzanne Nolet, BSc 1-514-890-8000 ext 26359 suzanne.nolet@crchum.qc.ca

Locations
Belgium
Centre hospitalier universitaire de Liège Recruiting
Liège, Belgium
Contact: Felix Scholtes, MD    04 242 52 00    felix.scholtes@chu.ulg.ac.be   
Principal Investigator: felix Scholtes, MD         
Canada, Alberta
Foothills Medical Center Recruiting
Calgary, Alberta, Canada, T2N 2T9
Contact: Karla Ryckborst    (403) 944-1110    Karla.Ryckborst@albertahealthservices.ca   
Principal Investigator: John Wong, MD         
University of Alberta Hospital Recruiting
Edmonton, Alberta, Canada, T6G 2B7
Principal Investigator: Max Findlay, PhD         
Principal Investigator: Tim Darsaut, MD,MSc         
Canada, Nova Scotia
QEII Health Sciences Centre Active, not recruiting
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
Ottawa Hospital Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Betty Anne Schwarz, RN    (613) 798-5555    baschwarz@toh.on.ca   
Contact: Christina Tsoukanas    (613) 798-5555    ctsoukanas@toh.on.ca   
Canada, Quebec
Centre hospitalier de l'Université de Montréal - CHUM Recruiting
Montreal, Quebec, Canada, H2L 4M1
Contact: Jean Raymond, MD    514-890-8000 ext 27235    jean.raymond@umontreal.ca   
Contact: Suzanne Nolet    514-890-8000 ext 26359    Suzanne.Nolet@crchum.qc.ca   
Sponsors and Collaborators
Centre hospitalier de l'Université de Montréal (CHUM)
Canadian Institutes of Health Research (CIHR)
Centre de Recherche du Centre Hospitalier de l'Université de Montréal
University of Alberta
Investigators
Principal Investigator: Tim Darsaut, MD University of Alberta
Principal Investigator: Jean Raymond, MD Université de Montréal
  More Information

No publications provided by Centre hospitalier de l'Université de Montréal (CHUM)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Jean Raymond, MD, Centre hospitalier de l'Université de Montréal (CHUM)
ClinicalTrials.gov Identifier: NCT01139892     History of Changes
Other Study ID Numbers: ND09.282, CIHR; MOP119554
Study First Received: June 2, 2010
Last Updated: March 3, 2015
Health Authority: Canada: Ethics Review Committee

Keywords provided by Centre hospitalier de l'Université de Montréal (CHUM):
Unruptured aneurysm
endovascular treatment
surgical treatment
randomized
intracranial aneurysm

Additional relevant MeSH terms:
Aneurysm
Intracranial Aneurysm
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Intracranial Arterial Diseases
Nervous System Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on April 23, 2015