Comprehensive Aneurysm Management for Brain Aneurysms

(CAM Trial)

Recruiting at 6 trial locations

Overseen By Jean Raymond, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Disqualifiers: Intracranial hemorrhage, AVM-associated aneurysms, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

Duration: 6-12 weeks

2000 Participants Needed

Trial Summary

What is the purpose of this trial?

The uncertainty regarding the management of Unruptured Intracranial Aneurysms (UIAs) has not progressed in the last 30 years. The fundamental ethical basis for this study is that physicians should only offer a risky preventive treatment when it has been shown to be beneficial. Before that, such treatment should be offered as an RCT. The CAM trial offers a comprehensive framework, so that all patients confronted with the clinical dilemma can be offered participation. The prinicpal questions to be addressed are : 1. do patients with UIAs, considered for curative treatments, have a better long-term clinical outcome with active treatment or conservative management? 2. when patients are considered ineligible for conservative management, and surgical and endovascular management are both judged reasonable, do patients with UIAs have a better long-term clinical outcome with surgical or endovascular management? The primary hypothesis for patients allocated to at least 2 options, one of which is conservative management is: the 10 year combined neurological morbidity and mortality (mRS\>2) will be reduced from 24% to 16% (beta 80%; alpha 0.048; sample size 961 patients (836 plus 15% losses to FU and cross-overs) with active treatment. This study is designed as a pragmatic, comprehensive way to address the unruptured aneurysm clinical dilemma, combining large simple RCTs whenever patients are judged eligible for more than one management option, or otherwise a registry of each option. All patients with one or more UIAs will be eligible for participation in either a registry or one of the trials. Patients will be followed for 10 years according to a standard of car follow-up schedule. The primary outcome is survival without neurological dependency (mRS\<3) at 10 years. The secondary outcomes are: 1. the incidence of SAH during follow-up and related morbidity and mortality; 2. the morbidity and mortality related to endovascular or surgical treatment of the UIA at one year; 3. overall mortality at 1, 5 and 10 years; 4. overall morbidity (mRS\>2) at 1, 5 and 10 years; 5. length of hospitalization; 6. discharge to location other than home

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Comprehensive Aneurysm Management for Brain Aneurysms?

Research shows that endovascular treatment can improve outcomes for patients with ruptured brain aneurysms compared to surgical clipping, although recurrences can occur. Flow diversion is a newer option that helps treat large or complex aneurysms that are difficult to manage with traditional methods like surgical clipping or endovascular coiling. ^{1 2 3 4 5}

Is the treatment for brain aneurysms generally safe for humans?

Endovascular coiling is generally considered safer than surgical clipping for treating brain aneurysms, as it tends to have lower risks of complications like brain tissue damage and infections. However, stent-assisted coiling has been associated with higher complication rates, so it's important to discuss options with a healthcare provider. ^{3 6 7 8 9}

How is the Comprehensive Aneurysm Management treatment for brain aneurysms different from other treatments?

The Comprehensive Aneurysm Management treatment is unique because it combines both endovascular (inside the blood vessel) and microsurgical techniques, offering options like flow diversion and endoscope-assisted microneurosurgery, which are particularly useful for treating complex or large aneurysms that are difficult to manage with traditional methods like clipping or coiling alone. ^{5 10 11 12 13}

Research Team

Tim Darsaut, MD

Principal Investigator

Neurosurgeon University of Alberta Health

Eligibility Criteria

This trial is for patients with at least one documented brain aneurysm (excluding cavernous aneurysms). It's not for those who can't consent, have had a recent intracranial hemorrhage, or have aneurysms associated with arteriovenous malformation (AVM).

Inclusion Criteria

I have a documented brain aneurysm, but not in the cavernous part.

Exclusion Criteria

I have not had a brain bleed in the last 30 days.

I am unable to understand and give consent for treatment.

I have aneurysms linked to my arteriovenous malformation (AVM).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either conservative management or interventional therapy (neurosurgery or endovascular procedure) based on randomization and clinical judgment

6-12 weeks

1 visit (in-person) for treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, with routine clinic visits and imaging

10 years

Visits at 6-12 weeks, 1 year, 5 years, and 10 years

Long-term Monitoring

Participants continue to be monitored for long-term outcomes such as survival without neurological dependency and incidence of SAH

10 years

Treatment Details

Interventions

• Endovascular Interventions
• Microsurgery

Trial Overview The study compares long-term outcomes of active treatment versus conservative management for unruptured brain aneurysms. It also evaluates whether microsurgery or endovascular interventions are more effective when surgery is necessary.

Participant Groups

Group I: Conservative Management Active Control 1 Intervention

Monitoring with pharmacological therapy if need arises.

Group II: Interventional Therapy Active Control 1 Intervention

Neurosurgery or Endovascular procedure

Endovascular Interventions is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Endovascular Interventions for:

• Unruptured Intracranial Aneurysms

Approved in United States as Endovascular Interventions for:

• Unruptured Intracranial Aneurysms

Approved in Canada as Endovascular Interventions for:

• Unruptured Intracranial Aneurysms

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

University of Alberta

Collaborator

Trials

957

Recruited

437,000+

Findings from Research

In a study of 92 patients with middle cerebral artery aneurysms, microsurgical clipping resulted in significantly higher aneurysm occlusion rates (96.3%) compared to endovascular treatment (78.9%).

However, endovascular treatment showed better long-term clinical outcomes with 100% of patients achieving a modified Rankin Scale score of 1 or less, and it had no permanent treatment-associated morbidity, while clipping had a 9.3% rate of complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microsurgical clipping and endovascular treatment of middle cerebral artery aneurysms in an interdisciplinary treatment concept: Comparison of long-term results. Schwartz, C., Aster, HC., Al-Schameri, R., et al.[2022]

In a study involving 16 canine arteries, endothelial denudation before coil embolization significantly improved the occlusion rates, with 75% of denuded arteries remaining occluded at 3 and 12 weeks, compared to all non-denuded arteries recanalizing.

Aneurysms treated with coils without prior denudation showed worse angiographic scores at 12 weeks, indicating that endothelial denudation may be a crucial step to enhance the long-term efficacy of endovascular treatment for intracranial aneurysms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of the endothelial lining in recurrences after coil embolization: prevention of recanalization by endothelial denudation. Raymond, J., Guilbert, F., Metcalfe, A., et al.[2016]

In a study of 291 patients with unruptured intracranial aneurysms, surgical clipping was found to be more effective than endovascular treatment, with a lower incidence of treatment failure (9% vs. 19%) at one year.

While clipping showed better efficacy, it was associated with higher rates of neurologic deficits and longer hospital stays compared to endovascular treatment, indicating a trade-off between effectiveness and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pragmatic Randomized Trial Comparing Surgical Clipping and Endovascular Treatment of Unruptured Intracranial Aneurysms. Darsaut, TE., Findlay, JM., Bojanowski, MW., et al.[2023]

A new clipping simulation for training neurosurgeons was developed, which uses a simple setup with a monoscopic display, mouse, and keyboard, allowing for effective practice on aneurysm clipping.

The simulation's effectiveness was enhanced by visualizing distances and forces, with findings showing that distance visualizations were crucial for proper navigation of the clip, as confirmed by both quantitative surveys and qualitative expert evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Distance and force visualisations for improved simulation of intracranial aneurysm clipping. Allgaier, M., Neyazi, B., Preim, B., et al.[2022]

Flow diversion is an FDA-approved treatment for brain aneurysms that effectively redirects blood flow away from the aneurysm, promoting the growth of a new endothelial lining, which leads to high cure rates and low complication rates.

This innovative technique has become a preferred option for treating large or complex aneurysms, particularly those that are wide-necked, and ongoing clinical trials are expected to further validate its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Flow Diversion for the Treatment of Intracranial Aneurysms. Walcott, BP., Stapleton, CJ., Choudhri, O., et al.[2022]

In a study of 186 patients with acute aneurysmal subarachnoid hemorrhage, endovascular coiling resulted in significantly lower rates of symptomatic vasospasm and cerebral infarction compared to surgical clipping.

Both treatment methods led to similar rates of good clinical recovery after 12 months, with 75% of patients in the coiling group and 69.7% in the clipping group achieving good outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of endovascular coiling versus surgical clipping in the treatment of ruptured intracranial aneurysms. Li, ZQ., Wang, QH., Chen, G., et al.[2017]

Stent-assisted coiling (SAC) of unruptured intracranial aneurysms is a safe treatment option, showing no increased risk of complications or mortality compared to traditional methods like coiling or clipping, despite having a higher initial cost.

While SAC had a higher rate of residual aneurysms immediately after treatment (75% vs 52% for coiling and 19% for clipping), this difference diminished at follow-up, indicating that SAC can be effective in the long term, especially for larger aneurysms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and cost of stent-assisted coiling of unruptured intracranial aneurysms compared with coiling or clipping. Frontera, JA., Moatti, J., de los Reyes, KM., et al.[2014]

Coiling treatment for aneurysmal subarachnoid hemorrhage is associated with better clinical outcomes compared to clipping, especially in patients with a good preoperative condition, as shown in a meta-analysis of 27 studies including randomized controlled trials and observational studies.

While coiling reduces the unfavorable outcome rate, it also carries a higher risk of rebleeding compared to clipping, which has a better complete occlusion rate, indicating a trade-off between immediate outcomes and long-term risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clipping versus coiling for ruptured intracranial aneurysms: a systematic review and meta-analysis. Li, H., Pan, R., Wang, H., et al.[2022]

Endovascular coiling is currently preferred over microsurgical clipping for treating unruptured intracranial aneurysms (UIA) due to its lower associated risks of complications like cerebrospinal fluid leakage and infection, as well as reduced mortality and disability rates.

This study aims to provide a direct comparison of the long-term safety and efficacy of endovascular coiling versus surgical clipping in a randomized controlled trial, assessing outcomes such as disability and recurrence rates over 6 months and 1 year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

To clip or to coil for unruptured intracranial aneurysm?: A protocol of randomized controlled trial. Huang, X., Yan, G., Qin, Z., et al.[2021]

The study evaluated the endoscopic and microsurgical techniques (EAM) in treating 206 intracranial aneurysms in 173 patients over a 10-year period, finding no surgical mortality and rare complications related to endoscopic procedures, indicating a high safety profile.

EAM showed improved efficacy based on the anatomical locations and sizes of the aneurysms, with the technique's success being enhanced by proper surgical training and the use of specialized equipment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endoscope-assisted microneurosurgery for intracranial aneurysms. Galzio, RJ., Di Cola, F., Raysi Dehcordi, S., et al.[2022]

Some cerebral aneurysms cannot be treated effectively with standard clipping or coiling, necessitating alternative surgical strategies such as parent artery occlusion and flow redirection.

Understanding the factors that predict the failure of conventional treatments is crucial for determining the best approach for complex aneurysms, ensuring that patients receive the most effective care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical strategies for aneurysms deemed unclippable and uncoilable. McLaughlin, N., Gonzalez, N., Martin, NA.[2016]

In a study of 12 patients with complex intracranial aneurysms, a combined approach of surgery and endovascular therapy resulted in a 92% complete elimination rate of aneurysms, demonstrating high efficacy in treatment.

No patients experienced repeat bleeding during a follow-up period averaging 23 months, and there were no deaths, indicating a strong safety profile for the combined management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complex intracranial aneurysms: combined operative and endovascular approaches. Hacein-Bey, L., Connolly, ES., Mayer, SA., et al.[2019]

In a study of 15 patients with complex intracranial aneurysms, extracranial-intracranial (EC-IC) bypass surgery showed promising results, with 13 out of 15 patients achieving good or excellent outcomes after a follow-up period averaging 15 months.

The surgery had a low mortality rate (0%) and a long-term bypass patency rate of 86.7%, indicating that while there was some morbidity (20%), the procedure is generally safe and effective for managing complex aneurysms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Result of extracranial-intracranial bypass surgery in the treatment of complex intracranial aneurysms : outcomes in 15 cases. Park, EK., Ahn, JS., Kwon, DH., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Microsurgical clipping and endovascular treatment of middle cerebral artery aneurysms in an interdisciplinary treatment concept: Comparison of long-term results. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Role of the endothelial lining in recurrences after coil embolization: prevention of recanalization by endothelial denudation. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

A Pragmatic Randomized Trial Comparing Surgical Clipping and Endovascular Treatment of Unruptured Intracranial Aneurysms. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

Distance and force visualisations for improved simulation of intracranial aneurysm clipping. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Flow Diversion for the Treatment of Intracranial Aneurysms. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Outcomes of endovascular coiling versus surgical clipping in the treatment of ruptured intracranial aneurysms. [2017]

7. England pubmed.ncbi.nlm.nih.gov

Safety and cost of stent-assisted coiling of unruptured intracranial aneurysms compared with coiling or clipping. [2014]

8. United States pubmed.ncbi.nlm.nih.gov

Clipping versus coiling for ruptured intracranial aneurysms: a systematic review and meta-analysis. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

To clip or to coil for unruptured intracranial aneurysm?: A protocol of randomized controlled trial. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Endoscope-assisted microneurosurgery for intracranial aneurysms. [2022]

11. France pubmed.ncbi.nlm.nih.gov

Surgical strategies for aneurysms deemed unclippable and uncoilable. [2016]

12. United States pubmed.ncbi.nlm.nih.gov

Complex intracranial aneurysms: combined operative and endovascular approaches. [2019]

13. Korea (South) pubmed.ncbi.nlm.nih.gov

Result of extracranial-intracranial bypass surgery in the treatment of complex intracranial aneurysms : outcomes in 15 cases. [2022]