The Canadian UnRuptured Endovascular Versus Surgery Trial (CURES)

Intracranial Aneurysms Clinical Trial

— CURES  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01139892
• Other study ID #: ND09.282
• Secondary ID: CIHR; MOP119554
• Status: Completed
• Start date: September 26, 2010
• Est. completion date: October 2022

Study information

• Verified date: July 2023
• Source: Centre hospitalier de l'Université de Montréal (CHUM)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 291
• Est. completion date: October 2022
• Est. primary completion date: October 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aneurysm
• Intracranial Aneurysm
• Intracranial Aneurysms

Intervention

Procedure:
• Surgical management

• Endovascular management

Locations

Country	Name	City	State
Belgium	Centre hospitalier universitaire de Liège	Liège
Canada	Foothills Medical Center	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Centre hospitalier de l'Université de Montréal - CHUM	Montreal	Quebec
Canada	Ottawa Hospital	Ottawa	Ontario
France	CHRU de Lille	Lille

Sponsors (3)

Lead Sponsor	Collaborator
Centre hospitalier de l'Université de Montréal (CHUM)	Centre de Recherche du Centre Hospitalier de l'Université de Montréal, University of Alberta

Countries where clinical trial is conducted

Belgium,  Canada,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Occurrence of a "major" (saccular) angiographic aneurysm recurrence.	Occurrence of a "major" (saccular) angiographic aneurysm recurrence.	1 year
Secondary	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
Secondary	Hospitalization lasting more than 5 days	This end-point will be recorded by the local treating physician on discharge.	6-weeks post-treatment
Secondary	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