Angiotensin II Receptor Blockade in Vascular Ehlers Danlos Syndrome (ARCADE)

• Register: ClinicalTrials.gov
• Last refreshed on: 11 March 2024
• Main ID: NCT02597361
• Date of registration: 23/10/2015
• Prospective Registration: Yes
• Primary sponsor: Assistance Publique - Hôpitaux de Paris
• Public title: Angiotensin II Receptor Blockade in Vascular Ehlers Danlos Syndrome (ARCADE) ARCADE
• Scientific title: Angiotensin II Receptor Blockade in Vascular Ehlers Danlos Syndrome: a Double Blind, Randomized, Placebo Controlled, Multicenter Trial.
• Date of first enrolment: January 2016
• Target sample size: 61
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02597361
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

France

Contacts

• Name: Xavier JEUNEMAITRE, MD,PHD
• Affiliation: AP-HP, INSERM

Key inclusion & exclusion criteria

Inclusion Criteria:

- Patients with genetically-proven vEDS (presence of a pathogenic mutation at the COL3A1
gene);

- Age =18 years and <70 years;

- Men and women with reliable contraception or negative beta-HCG at screening;

- Celiprolol at the optimal tolerated dose since at least 12 weeks;

- vEDS patient fully intolerant to celiprolol but not treated with any other drug active
on the vascular system, except another beta-blocker;

- No compelling indication for ARB therapy (renal infarction, hypertension, proteinuric
nephropathy, chronic heart failure, myocardial infarction, stroke);

- Estimated glomerular filtration rate (GFR) = 30ml/min/1,73m2 (MDRD Formula);

- Normal or clinically acceptable 12-lead ECG;

- Written informed consent to participate in the study.

Exclusion Criteria:

General criteria

- Unlikely to co-operate in the study and/or poor compliance anticipated by the
investigator, e.g., uncooperative attitude, inability to return for follow-up visit,
and unlikelihood of completing the study;

- Participation in another interventional therapeutic study at the same time or within 3
months prior to the beginning of the present study;

- Participant not affiliated to the French social security;

- No written informed consent;

- Severe contrast media allergy, not amenable to pre-treatment Medical and therapeutic
criteria

- History of previous symptomatic visceral complication (any CV event, pulmonary or
digestive event) in the 3 months preceding the inclusion;

- Formal indication for an antihypertensive medication (office BP =140/90 mmHg on
celiprolol on at least two separated visits, confirmed by daytime ambulatory BP or
home BP = 135/85 mmHg);

- Concomitant treatment with renin-angiotensin-aldosterone system blocking agents apart
from the study drug, e.g. ACEI, ARB or aldosterone-antagonist or any renin inhibitor,
if given for an elective indication (heart failure, renal infarction, chronic kidney
disease, proteinuria, myocardial infarction, stroke);

- Any cardiac condition that justifies a specific medical care (i.e. second or third
degree auriculo-ventricular block, potentially life threatening arrhythmia or other
uncontrolled arrhythmia or persistent arrhythmia, clinically significant valvular
heart disease);

- Known significant renal artery stenosis with evidence of renal ischemia (on Duplex
ultrasound, CTA, or other exam);

- Any concurrent life threatening condition other than vEDS with a life expectancy less
than 2 years;

- Likely allergy or hypersensitivity to irbesartan, based on known allergies to drugs of
the same class, or which in the opinion of the investigator suggests an increased
potential for an adverse hypersensitivity as well as known or suspected
contraindications to the study drug;

- Any condition that in the opinion of the investigator would jeopardize the evaluation
of efficacy or safety;

- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
female after conception and until the termination of gestation, confirmed by a
positive Human Chorionic Gonadotropin (hCG) laboratory test (>5 mIU/ml);

- Women of child-bearing potential (WOCBP) without reliable contraception.



Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Ehlers-Danlos Syndrome, Vascular Type

Intervention(s)

Drug: Placebo

Drug: Irbesartan

Primary Outcome(s)

Arterial lesions [Time Frame: 2 years]

Cardiovascular morbidity and mortality [Time Frame: 2 years]

Secondary Outcome(s)

Change in estimated glomerular filtration rate (MDRD) [Time Frame: 2 years]

Compliance to treatment [Time Frame: 2 years]

Rate of any symptomatic cardiovascular event [Time Frame: 2 years]

Time to first symptomatic clinical morbid and fatal events [Time Frame: 2 years]

Changes in PWV (Pulse Wave Velocity) [Time Frame: 2 years]

Number of unplanned hospitalization for any vEDS related event [Time Frame: 2 years]

Occurrence of new asymptomatic arterial lesions (aneurysm, dissection), detected by a systematic CTA [Time Frame: 2 years]

Tolerability and safety of the irbesartan assessed by orthostatic hypotension, plasma creatinine, plasma K+ evaluated at each visit [Time Frame: 2 years]

Changes in large arteries properties (diameter, wall stress, stiffness) [Time Frame: 2 years]

Decrease in office systolic/diastolic BP [Time Frame: 2 years]

Quality of life [Time Frame: 2 years]

Total number of arterial lesions detected by vascular DUS [Time Frame: 2 years]

Total number of arterial lesions worsened during follow-up [Time Frame: 2 years]

Secondary ID(s)

P140918

2015-001065-76

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Ministry of Health, France