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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find the best way to treat unruptured brain aneurysms, which are bulges in blood vessels that haven't burst. Researchers will compare active treatments, such as surgery or endovascular procedures (using a catheter to repair the blood vessel from inside), against simply monitoring the condition to determine which leads to better long-term health. People with a documented brain aneurysm, but no recent brain bleeding or related conditions, are eligible. The goal is to assess whether active treatment helps patients live without major neurological issues over the next 10 years. As an unphased trial, participants contribute to important research that may improve future treatment strategies.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that endovascular methods for treating brain aneurysms are generally safe, though some risks exist. Some studies indicate that flow-diverter stents can cause complications during the procedure. However, these stents effectively treat aneurysms, achieving high success rates in closing the aneurysm, ranging from 77% to 96% over time.

Traditional surgery also yields promising results. Studies have found that 97.98% of patients experienced good neurological outcomes two years post-surgery. The procedure successfully closes 91.8% of unruptured aneurysms, effectively sealing the aneurysm in most cases.

Both treatments have their pros and cons but are generally well-tolerated. Consulting healthcare professionals is important to determine the best option. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the treatments for brain aneurysms in this trial because they explore comprehensive management strategies combining endovascular interventions and microsurgery. Unlike the standard of care, which typically involves either surgical clipping or coiling, these treatments aim to personalize the approach based on the aneurysm's characteristics and the patient's condition. Endovascular interventions offer a minimally invasive option that can be less taxing on the body, while microsurgery provides direct access for precise repair. This trial could lead to more tailored, effective treatment plans, potentially improving outcomes for patients with brain aneurysms.

What evidence suggests that this trial's treatments could be effective for brain aneurysms?

This trial will compare different management strategies for brain aneurysms. Studies have shown that certain procedures, such as flow diverter stents, which are part of the endovascular interventions in this trial, can effectively treat brain aneurysms, achieving complete closure in about 84.5% of cases. These devices redirect blood flow away from the aneurysm, allowing the blood vessel to heal. Research also shows that using coils in endovascular therapy yields good results, especially when combined with other tools like balloons. In contrast, microsurgery, specifically clipping, is another treatment option in this trial and has a very high success rate, closing aneurysms in 91.8% of cases. Most patients recover well, with nearly 98% experiencing positive outcomes within two years after the procedure. Both treatments offer promising options for managing unruptured brain aneurysms. ^{3 4 6 7 8}

Who Is on the Research Team?

Tim Darsaut, MD

Principal Investigator

Neurosurgeon University of Alberta Health

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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 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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11577147/

Effectiveness of Flow Diverter Stents in the Treatment of ... By the results of the current study the complete occlusion rate was found to be 84.5% in aneurysms of all sizes, types and locations. Also, ...

2. ahajournals.org ahajournals.org/doi/10.1161/SVIN.123.001118

Systematic Review and Meta‐Analysis of Endovascular ... We observed that the coil‐based endovascular therapy provides acceptable rates of complete occlusion, and these rates are improved in balloon‐assisted coils.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5435202/

Cerebral aneurysm treatment: modern neurovascular ... Flow diversion has proven promising to overcome limitations of traditional endovascular coiling techniques for the treatment of sidewall aneurysms; however, the ...

4. americanjir.com americanjir.com/endovascular-treatment-on-ruptured-wide-neck-intracranial-aneurysms-single-center-retrospective-study-on-efficacy-and-safety/

Endovascular treatment on ruptured wide-neck intracranial ... Our study specifically found superior efficacy of flow diversion with or without adjunctive coiling compared to other endovascular modalities, ...

5. ajnr.org ajnr.org/content/43/7/1004

The Safety and Efficacy of Flow Diversion versus ... The placement of a flow diverter may lead to more procedure-related complications, but there is no difference in safety, and it is more effective in the long ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36150896/

Long-term outcomes of flow diversion for unruptured ... The pooled occlusion rates after flow diversion treatment for unruptured intracranial brain aneurysms were 77%, 87.4%, 84.5%, 89.4%, 96% for ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4757311/

Endovascular treatment of cerebral aneurysms using flow ... Flow-diverter devices (FDDs) are new-generation stents placed in the parent artery at the level of the aneurysm neck to disrupt the intra-aneurysmal flow.

8. dirjournal.org dirjournal.org/pdf/beb8919b-f013-4ea1-b1c8-40332e840fe1/articles/dir.2024.242903/366-371.pdf

Safety and efficacy of flow diverter stents in the treatment of ... This study reports our center's initial experience treating bifurcation aneurysms with FD devices, documenting occlusion outcomes using the O' ...