Treatment in Thoracic Aortic Aneurysm: Surgery vs Surveillance

NCT ID: NCT03536312

Last Updated: 2025-09-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

610 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-09-01

Study Completion Date

2035-05-31

Brief Summary

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The ascending aorta conducts blood from the heart to the rest of the body. The ascending aorta can become enlarged, and the risk of tearing and rupturing becomes higher with larger aorta. When the ascending aorta tears or ruptures, the risk dying is high even if surgery is done as soon as possible. Traditionally, when the ascending aorta gets above 5.5 cm, surgery is recommended to replace the aorta. However, this threshold is based relatively weak evidence, and sometimes patients with smaller aorta can tear or rupture. On the other hand, surgery carries its own risk as well. Since there are risk of waiting or doing surgery, there is currently no great support for either approach for patients with a smaller aorta. In the TITAN SvS trial, patients with an ascending aorta between 5.0 to 5.5 cm is assigned by chance to the early surgery group, in which they will undergo replacement of aorta, or the surveillance group, in which they will be closely monitored. The chance of dying or suffer tearing or rupture of aorta between the two groups will be compared. The result of the trial will guide future practice for patients with enlarged ascending aorta.

This is a prospective, multi-centre randomized control trial that compares the all-cause mortality, aneurysm-related aortic events, rate of stroke, and quality of life for those patients undergoing early elective ascending aortic surgery to those patients undergoing surveillance. Patients referred for an ascending aortic aneurysm that meets the inclusion criteria will be randomized to the early elective surgery group or the surveillance group. Recruitment will end when the desired sample size is reached, and the patients will be followed for a minimum 2-year period. The primary objective of the trial is to compare the composite outcome of the all-cause mortality and incidence of acute aortic events between surveillance and elective ascending aortic surgery for patients with degenerative or bicuspid valve-related ascending aortic aneurysm after 2 years of follow up. The hypothesis is that the early surgery group will have a significantly lower all-cause mortality and incidence of acute aortic events at 2 years of follow up compare to the surveillance group. The result of this trial will provide evidence based guidance in the appropriate management of ascending aortic aneurysm based on the size criteria, and establish a large database for future investigations.

Detailed Description

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All patients referred electively to a participating investigator for the evaluation of their ascending aortic aneurysm will be screened for study eligibility. Patients between the age of 18 and 79 with an asymptomatic ascending aortic aneurysm between 5.0 cm and 5.4 cm in maximal diameter are entered into the randomization study. Patients with ascending aortic aneurysm with a diameter of 4.5 cm - 4.9 cm will be observed with serial CT, and will be considered for enrollment into the trial once the aneurysm reaches 5.0 cm.

When the patient is first assessed in clinic, a pre-randomization evaluation will be completed. Baseline information of the patient, including demographics, past medical history, family history, medications, smoking habits, and the characteristics of the aneurysm, is collected. Measurements including weight, height, heart rate, blood pressure in both arms, is recorded. Basic blood work, including hemoglobin, white cell count, platelets, electrolytes, creatinine, random blood sugar, HbA1c, and cholesterol profile is taken for analysis. An electrocardiograph, chest X-ray, and a CT scan from the surgeon's institution is also obtained. SF-36, the quality of life questionnaire, will be completed by the patient. Those patients that are suitable for the trial based on inclusion and exclusion criteria will then be randomized en-site through a computer-generated randomization program.

For the patients randomized to elective surgery group, the surgery is scheduled within 10-12 weeks of randomization. In the interim, the patient will be placed on maximal medical therapy for their aneurysm, including beta-blocker, statin, and blood pressure control, and the doses of these medication will be individualized based on each patient's own physiological response. The types of surgery (ascending aortic replacement, Bentall procedure, valve-sparing root replacement, etc.) will be at the discretion of the surgeon. The details of the surgery and the patient's course of postoperative hospital stay is recorded. The patient will be managed postoperatively according to routine hospital care. After discharge, patients will be seen at 1 months for their routine postoperative follow up, then annually counting from their index clinic visit before the surgery. At the first postoperative clinic visit, weight, height, heart rate, blood pressure in both arms, is recorded. Basic blood work, including hemoglobin, white cell count, platelets, electrolytes, creatinine is taken for analysis. An electrocardiograph and chest X-ray will be obtained. All subsequent clinic visits can be done in person or by phone conducted by a study coordinator. A CT scan will be obtained at all subsequent clinic visits. Mortality status and occurrence of acute aortic event or stroke in the previous year will be assessed at every annual clinic visit. Quality of life assessment by SF-36 questionnaire will be completed by the patient in person or by phone at 1 year and 2 years follow-up. Annual follow-up will continue until either the patient dies or the trial ends. Patients who are randomized to the surveillance group will be placed on maximal medical therapy for their aneurysm, including beta-blocker, statin, and blood pressure control. The doses of these medication will be individualized based on each patient's own physiological response. The patients will undergo a CT scan of the chest at the first clinic visit then annually for the duration of the study. All CTs will be uploaded to a core CT imaging lab where the image will be reviewed by a Radiologist. If the aneurysm grows beyond 5.5 cm or the patient develop symptoms, the surgeon will consider the patient for surgery. At all clinic visits, in addition to CT, weight, height, heart rate, blood pressure in both arms, an electrocardiograph, and a chest X-ray will be obtained. The surveillance visits continue until either the patient dies, the trial ends, or surgery is considered. If the patient is no longer considered a suitable candidate for surgery or refuse surgery, follow-up will continue, and the patient will no longer be a part of the trial and will only be registered in the side arm.

Conditions

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Ascending Aortic Aneurysm Enlargement Ascending Aorta Aneurysm

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Patients between the age of 18 and 79 with an asymptomatic ascending aortic aneurysm between 5.0 cm and 5.4 cm in maximal diameter are entered into the randomization study.
Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Surveillance Arm

Patients in the Non-Operative Registry will be followed in clinic annually with a CT scan to monitor the status of their ascending aortic aneurysm, until the end of the study, the occurrence of an aortic event, or death.

Group Type NO_INTERVENTION

No interventions assigned to this group

Surgery/Treatment Arm

Patients in the Operative Registry will have thoracic aortic surgery

Group Type OTHER

Thoracic Aortic Surgery

Intervention Type PROCEDURE

Thoracic aortic surgery to treat thoracic aortic aneurysm

Interventions

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Thoracic Aortic Surgery

Thoracic aortic surgery to treat thoracic aortic aneurysm

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

1. Patients between the age of 18 and 79 inclusive.
2. Ascending aortic aneurysm between 5.0cm and 5.4cm in maximal diameter as measured by CT with contrast.
3. Patients with ascending aortic aneurysm with a diameter of 4.5 cm - 4.9 cm will be observed with serial CT, and will be considered for enrollment into the trial once the aneurysm reaches 5.0 cm.

Exclusion Criteria

1. Patients who refused to be randomized
2. Patients with symptomatic attributable to ascending aortic aneurysms
3. Patients who are unable to provide informed consents
4. Patients who are unable to attend for regular follow-up/ remain compliant with protocol
5. Previous cardiac surgery
6. Patients whose primary indication for cardiac surgery is non-AsAA related
7. Known AsAA expansion rate exceeding 0.5 cm/year during the past 5 years
8. Arch aneurysms with no ascending aorta involvement (no aneurysmal segments before the innominate artery)
9. Ascending aortic and arch aneurysm with descending thoracic aorta involvement
10. Patients with known connective tissue disease (E.g. Marfan syndrome, Loey-Dietz syndrome, Turner syndrome etc) syndrome, etc.)
11. Patients with possible genetic aortopathies (eg known family history of aortic aneurysms/premature aortic dissections/ruptures)
12. Patients with inflammatory arteritis (e.g. takayasu's arteritis, syphilitic arteritis, etc.)
13. Female patients who are pregnant or planning to become pregnant
14. Patients who have a history or presence of a medical condition or disease or psychiatric condition that in the investigator's assessment would render the subject ineligible for study participation.
15. Patients who, in the opinion of the investigator, are deemed unfit for surgery for reasons that may include:

* Severe pulmonary disease
* Cr = 250umol/L
* Child Pugh Class B or C
* NYHA III or IV
* MI within the last 6 months
* Major surgical procedure or angioplasty within 3 months
* Expected survival less than 5 years because of other disease (e.g. invasive cancer)
Minimum Eligible Age

18 Years

Maximum Eligible Age

79 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Calgary

OTHER

Sponsor Role collaborator

University Health Network, Toronto

OTHER

Sponsor Role collaborator

Institut universitaire de cardiologie et de pneumologie de Québec, University Laval

OTHER

Sponsor Role collaborator

Hamilton General Hospital

UNKNOWN

Sponsor Role collaborator

Montreal Heart Institute

OTHER

Sponsor Role collaborator

University of Pennsylvania

OTHER

Sponsor Role collaborator

Massachusetts General Hospital

OTHER

Sponsor Role collaborator

McGill

UNKNOWN

Sponsor Role collaborator

University of Michigan

OTHER

Sponsor Role collaborator

Ohio State University

OTHER

Sponsor Role collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role collaborator

Washington University School of Medicine

OTHER

Sponsor Role collaborator

University Hospitals Cleveland Medical Center

OTHER

Sponsor Role collaborator

University of Alberta

OTHER

Sponsor Role collaborator

Mayo Clinic

OTHER

Sponsor Role collaborator

Medical University of South Carolina

OTHER

Sponsor Role collaborator

Nova Scotia Health Authority

OTHER

Sponsor Role collaborator

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

OTHER

Sponsor Role collaborator

Horizon Health Network

OTHER

Sponsor Role collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role collaborator

San Francisco Veterans Affairs Medical Center

FED

Sponsor Role collaborator

Ottawa Heart Institute Research Corporation

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Munir Boodhwani, MD

Role: PRINCIPAL_INVESTIGATOR

Ottawa Heart Institute Research Corporation

Jehangir Appoo, MD

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Locations

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University of California at San Francisco Medical Center

San Francisco, California, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status RECRUITING

University of Michigan

Ann Arbor, Michigan, United States

Site Status RECRUITING

Mayo Clinic

Rochester, Minnesota, United States

Site Status RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

Site Status RECRUITING

The Valley Hospital, Inc

Ridgewood, New Jersey, United States

Site Status RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status RECRUITING

Duke University

Durham, North Carolina, United States

Site Status RECRUITING

University Hospitals Cleveland

Cleveland, Ohio, United States

Site Status RECRUITING

Ohio State University Medical Center

Columbus, Ohio, United States

Site Status RECRUITING

The Trustees of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

MUSC Health University Medical Center

Charleston, South Carolina, United States

Site Status RECRUITING

University of Texas Health Science Centre

Houston, Texas, United States

Site Status RECRUITING

Baylor Scott & White Research Institute

Plano, Texas, United States

Site Status RECRUITING

University of Calgary

Calgary, Alberta, Canada

Site Status RECRUITING

Mazankowski Alberta Heart Institute

Edmonton, Alberta, Canada

Site Status RECRUITING

Horizon Health Network

Saint John, New Brunswick, Canada

Site Status RECRUITING

Nova Scotia Health Authority

Halifax, Nova Scotia, Canada

Site Status RECRUITING

Health Sciences North

Greater Sudbury, Ontario, Canada

Site Status RECRUITING

Hamilton General Hospital

Hamilton, Ontario, Canada

Site Status RECRUITING

London Health Sciences Centre

London, Ontario, Canada

Site Status RECRUITING

University of Ottawa Heart Institute

Ottawa, Ontario, Canada

Site Status RECRUITING

St. Michael's Hospital

Toronto, Ontario, Canada

Site Status NOT_YET_RECRUITING

Toronto General Hospital

Toronto, Ontario, Canada

Site Status RECRUITING

Montreal Heart Institute

Montreal, Quebec, Canada

Site Status RECRUITING

McGill University Health Centre

Montreal, Quebec, Canada

Site Status RECRUITING

Institut universitaire de cardiologie et de pneumologie de Québec

Québec, Quebec, Canada

Site Status RECRUITING

Countries

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United States Canada

Central Contacts

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Khatira Mehdiyeva

Role: CONTACT

613-696-7000

Alice Black

Role: CONTACT

613-696-7230

Facility Contacts

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Jenifer Kaufman

Role: primary

617-632-8956

Disrud Levi

Role: primary

507-284-2511

Allison Schuck

Role: primary

314-362-5000

Nisreen Zueiter

Role: primary

216-844-1000

Nimesh Desai, MD

Role: primary

Hannah Culpepper

Role: primary

843-792-7244

Nasim Boroumand

Role: primary

780-407-2667

Cynthia Ukeoma

Role: primary

902-473-2847

Munir Boodhwani, MD

Role: primary

613-696-7237

Azmat Sheikh

Role: backup

613-696-7000 ext. 13022

Philippe Demers, MD

Role: primary

References

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Guo MH, Appoo JJ, Wells GA, Chu M, Ouzounian M, Fortier J, Boodhwani M. Protocol for a randomised controlled trial for Treatment in Thoracic Aortic Aneurysm: Surgery versus Surveillance (TITAN: SvS). BMJ Open. 2021 May 26;11(5):e052070. doi: 10.1136/bmjopen-2021-052070.

Reference Type DERIVED
PMID: 34039580 (View on PubMed)

Other Identifiers

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20180007-01H

Identifier Type: -

Identifier Source: org_study_id

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