The Canadian UnRuptured Endovascular Versus Surgery Trial (CURES) (CURES)

Canadian Study on the Endovascular Treatment of Unruptured Intracranial Aneurysms Versus Surgical Treatment. A Randomized Comparison of Clinical and Angiographic Results of Intracranial Aneurysms

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.

Study Overview

• Status: Completed
• Conditions: Intracranial Aneurysms
• Intervention / Treatment: Procedure: Surgical management; Procedure: Endovascular management

• Study Type: Observational
• Enrollment (Actual): 291

Contacts and Locations

Study Locations

• Belgium
  • Liège, Belgium
    • Centre Hospitalier Universitaire de Liège
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Medical Center
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2X 0C1
      • Centre Hospitalier de l'Université de Montréal - CHUM
• France
  • Lille, France
    • CHRU de Lille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

primary care clinic

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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 Names: 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 Names: Arm 2: coiling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment failure	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.	One Year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morbidity and mortality: 2. Hospitalization >5 days : physician reporting. 3. Discharge other than to home: physician reporting.	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.	one year
Occurrence of morbidity (mRS >2) or mortality following treatment.	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.	6 weeks post-treatment
Failure of aneurysm occlusion	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.	1 year
Occurrence of a "major" (saccular) angiographic aneurysm recurrence.	Occurrence of a "major" (saccular) angiographic aneurysm recurrence.	1 year
Occurrence of an intracranial hemorrhage	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.	1 year
Hospitalization lasting more than 5 days	This end-point will be recorded by the local treating physician on discharge.	6-weeks post-treatment
Discharge following treatment to a location other than home	This end-point will be recorded by the local treating physician on discharge.	6-weeks post-treatment

Collaborators and Investigators

• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Collaborators: University of Alberta; Centre de Recherche du Centre Hospitalier de l'Université de Montréal
• Investigators: Principal Investigator: Tim Darsaut, MD, University of Alberta; Principal Investigator: Jean Raymond, MD, Université de Montréal

Publications and helpful links

General Publications

• Naggara O, Darsaut T, Trystram D, Tselikas L, Raymond J. Unruptured intracranial aneurysms: why we must not perpetuate the impasse for another 25 years. Lancet Neurol. 2014 Jun;13(6):537-8. doi: 10.1016/S1474-4422(14)70091-2. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2010
• Primary Completion (Actual): October 1, 2022
• Study Completion (Actual): October 1, 2022

Study Registration Dates

• First Submitted: June 2, 2010
• First Submitted That Met QC Criteria: June 8, 2010
• First Posted (Estimated): June 9, 2010

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: July 4, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: endovascular treatment; randomized; surgical treatment; intracranial aneurysm; Unruptured aneurysm
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Arterial Diseases; Aneurysm; Intracranial Aneurysm
• Other Study ID Numbers: ND09.282; CIHR; MOP119554 (Other Grant/Funding Number: Grant to CHUM Research Centre to Dr. Jean Raymond.)