Study of the Effectiveness of Telmisartan in Slowing the Progression of Abdominal Aortic Aneurysms (TEDY)

The purpose of this study is to determine if telmisartan is effective in slowing the progression of abdominal aortic aneurysms and reducing circulating concentrations of Abdominal Aortic Aneurysms (AAA) biomarkers.

Study Overview

• Status: Completed
• Conditions: Abdominal Aortic Aneurysm
• Intervention / Treatment: Drug: Placebo; Drug: Telmisartan

Detailed Description

Currently, the only management options for AAA are surgical (open or endovascular) based on ongoing follow-up with imaging at regular intervals. Telmisartan is currently approved for use in the United States by the Food and Drug Administration for management of hypertension. If telmisartan is found to be effective in slowing the progression of abdominal aortic aneurysms, this would provide a new treatment option for patients with AAA disease.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • VA Palo Alto Health Care System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 50-85 years of age and able to provide written informed consent
• AAA measuring a maximum diameter of 3.5-4.9 cm on CTA or ultrasound
• Stable medication regime for the last six months
• No current indication for AAA repair according to the treating physician or expectation that this will be revised within the next year
• High likelihood of compliance with treatment over 24 months

Exclusion Criteria:

• Renal impairment (i.e. creatinine >1.5x upper limit of normal [ULN])
• Known significant renal stenosis (>70%) of one or both renal arteries
• Chronic liver disease (i.e. cirrhosis or hepatitis) or abnormal liver function (i.e. ALT 1.5xULN)
• Electrolyte imbalance
• Active gout
• Current or planned usage of an AT1 blocker or ACE inhibitor
• Previous abdominal aortic surgery
• Currently pregnant or intend to become pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Telmisartan; One 40mg telmisartan pill given once daily for 24 months	Drug: Telmisartan
PLACEBO_COMPARATOR: Placebo; One 40mg placebo pill given once daily for 24 months	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of AAA growth assessed by total infrarenal aortic volume measured on computed tomography angiography (CTA)	Patients will be followed for two years following enrollment, with AAA growth determined by comparing total AAA volume at baseline and at two years between control and treatment groups.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in maximum infrarenal AAA diameter and aortic distensibility on repeat ultrasound	Interval assessments of ultrasound-determined diameter will also be performed to reduce the variability of individual ultrasound-derived aortic diameter measurements.	Comparison between two groups at baseline and two years.
Change in circulating concentrations of AAA biomarkers (serum OPG, OPN, MMP-9 and TGFB-1) on repeated samples		Comparison between baseline and 2 years (24 months) following enrollment
Quality of life assessed by the 12-item Assessment of Quality of Life (AQoL)		Comparison between baseline and 24 months between the two groups.

Collaborators and Investigators

• Sponsor: Palo Alto Veterans Institute for Research
• Collaborators: Medtronic; James Cook University, Queensland, Australia
• Investigators: Principal Investigator: Ronald L Dalman, M.D., PAIRE: Stanford University, VA Palo Alto Health Care System

Publications and helpful links

General Publications

• Golledge J, Tsao PS, Dalman RL, Norman PE. Circulating markers of abdominal aortic aneurysm presence and progression. Circulation. 2008 Dec 2;118(23):2382-92. doi: 10.1161/CIRCULATIONAHA.108.802074. No abstract available.
• Golledge J, Pinchbeck J, Tomee SM, Rowbotham SE, Singh TP, Moxon JV, Jenkins JS, Lindeman JH, Dalman RL, McDonnell L, Fitridge R, Morris DR; TEDY Investigators. Efficacy of Telmisartan to Slow Growth of Small Abdominal Aortic Aneurysms: A Randomized Clinical Trial. JAMA Cardiol. 2020 Dec 1;5(12):1374-1381. doi: 10.1001/jamacardio.2020.3524.
• Xuan H, Xu B, Wang W, Tanaka H, Fujimura N, Miyata M, Michie SA, Dalman RL. Inhibition or deletion of angiotensin II type 1 receptor suppresses elastase-induced experimental abdominal aortic aneurysms. J Vasc Surg. 2018 Feb;67(2):573-584.e2. doi: 10.1016/j.jvs.2016.12.110. Epub 2017 Apr 20.
• Morris DR, Cunningham MA, Ahimastos AA, Kingwell BA, Pappas E, Bourke M, Reid CM, Stijnen T, Dalman RL, Aalami OO, Lindeman JH, Norman PE, Walker PJ, Fitridge R, Bourke B, Dear AE, Pinchbeck J, Jaeggi R, Golledge J. TElmisartan in the management of abDominal aortic aneurYsm (TEDY): The study protocol for a randomized controlled trial. Trials. 2015 Jun 17;16:274. doi: 10.1186/s13063-015-0793-z. Erratum In: Trials. 2016;17:43.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 19, 2012
• Primary Completion (ACTUAL): November 10, 2018
• Study Completion (ACTUAL): November 10, 2018

Study Registration Dates

• First Submitted: September 5, 2012
• First Submitted That Met QC Criteria: September 7, 2012
• First Posted (ESTIMATE): September 11, 2012

Study Record Updates

• Last Update Posted (ACTUAL): May 26, 2020
• Last Update Submitted That Met QC Criteria: May 21, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: AAA; Abdominal Aortic Aneurysm; telmisartan
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Aortic Diseases; Aneurysm; Aortic Aneurysm; Aortic Aneurysm, Abdominal; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Telmisartan
• Other Study ID Numbers: DAL0041ARG; 22647 (OTHER: Stanford IRB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes