The Canadian UnRuptured Endovascular Versus Surgery Trial (CURES) (CURES)
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.
To compare the results of surgical and endovascular management strategies, in terms of:
- Overall mortality and morbidity at 1 and 5 years.
- The clinical efficacy and safety of a surgical or endovascular management strategy at 1 and 5 years
Hypotheses: Phase 1 Hypotheses:
- Surgical clipping of intradural, saccular, unruptured intracranial aneurysms is superior to endovascular management in terms of a lesser number of patients experiencing treatment failure.
- 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:
- Overall morbidity and mortality at one year.
- Occurrence of morbidity (mRS >2) or mortality following treatment.
- Occurrence of failure of aneurysm occlusion using the initial intended treatment modality.
- Occurrence of a "major" (saccular) angiographic aneurysm recurrence.
- Occurrence of an intracranial hemorrhage following treatment.
- Peri-treatment hospitalization lasting more than 5 days
- Discharge following treatment to a location other than home
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:
- One management strategy is superior to the other in terms of clinical outcome at five years.
- One management strategy is superior to the other in terms of clinical efficacy at five years.
|Intracranial Aneurysms||Procedure: Surgical management Procedure: Endovascular management|
|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|
- Treatment failure [ Time Frame: One Year ]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.
- Morbidity and mortality: 2. Hospitalization >5 days : physician reporting. 3. Discharge other than to home: physician reporting. [ Time Frame: one year ]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 ]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 ]
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 ]Occurrence of a "major" (saccular) angiographic aneurysm recurrence.
- Occurrence of an intracranial hemorrhage [ Time Frame: 1 year ]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 ]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 ]This end-point will be recorded by the local treating physician on discharge.
|Actual Study Start Date:||September 26, 2010|
|Estimated Study Completion Date:||June 2025|
|Estimated Primary Completion Date:||June 2020 (Final data collection date for primary outcome measure)|
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 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01139892
|Contact: Jean Raymond, MD||514-890-8000 ext firstname.lastname@example.org|
|Contact: Suzanne Nolet, CCRP||1-514-890-8000 ext email@example.com|
|Centre hospitalier universitaire de Liège||Recruiting|
|Contact: Felix Scholtes, MD 04 242 52 00 firstname.lastname@example.org|
|Principal Investigator: Felix Scholtes, MD|
|Foothills Medical Center||Completed|
|Calgary, Alberta, Canada, T2N 2T9|
|University of Alberta Hospital||Recruiting|
|Edmonton, Alberta, Canada, T6G 2B7|
|Contact: Sherry Knoppers Sherry.Knoppers@albertahealthservices.ca|
|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|
|Ottawa, Ontario, Canada, K1H 8L6|
|Contact: Betty Anne Schwarz, PhD, RN (613) 798-5555 email@example.com|
|Contact: Christina Tsoukanas (613) 798-5555 firstname.lastname@example.org|
|Principal Investigator: Howard Lesiuk, MD|
|Centre hospitalier de l'Université de Montréal - CHUM||Recruiting|
|Montreal, Quebec, Canada, H2L 4M1|
|Contact: Jean Raymond, MD 514-890-8000 ext 27235 email@example.com|
|Contact: Suzanne Nolet 514-890-8000 ext 26359 Suzanne.Nolet@crchum.qc.ca|
|CHRU de Brest||Recruiting|
|Contact: Jean-Christophe Gentric, MD 02 98 34 74 87 firstname.lastname@example.org|
|Principal Investigator: Jean-Christophe Gentric, MD|
|CHRU de Lille||Active, not recruiting|
|Principal Investigator:||Tim Darsaut, MD||University of Alberta|
|Principal Investigator:||Jean Raymond, MD||Université de Montréal|