Angiotensin II Receptor Blockade in Vascular Ehlers Danlos Syndrome (ARCADE)
Condition: Ehlers-Danlos Syndrome, Vascular Type
MeSH terms: Ehlers-Danlos Syndrome; Ehlers-Danlos Syndrome, Type IV; Syndrome
Study type: Interventional
Phase: Phase 3

Summary: 
      This study aims to verify the hypothesis that patients with Vascular Ehlers Danlos syndrome
      (vEDS) should benefit of the blockade of angiotensin (Ang) II noxious effects on their
      vasculature affected by a defect in type III collagen in addition to the effects celiprolol.
      This randomized, double blind, placebo controlled trial compares the administration of the
      Ang II type I receptor blocker (ARB) - irbesartan- to placebo over a 2-year period in vEDS
      patients with the main objective to reduce the incidence of both symptomatic and asymptomatic
      vascular events.
    

Detailed description: 
      vEDS is a rare life-threatening inherited condition due to mutations at the COL3A1 gene
      encoding the pro-alpha 1 chain of type III procollagen (OMIM #130050) with unpredictable and
      recurring arterial dissections/aneurysms starting in the early adulthood. The investigators
      have previously shown that a treatment with 200-400 mg per day of celiprolol, reduces both
      fatal and non-fatal vascular events in patients with vEDS. If tolerated, the treatment is now
      the standard treatment for vEDS. However, despite celiprolol , symptomatic and asymptomatic
      arterial events continue to occur in vEDS patients. Recent findings suggest a possible
      deleterious effect of endogenous Angiotensin II on medium size arteries in vEDS patients. The
      hypothesis of this study is that the blockade of endogenous Ang II will provide supplemental
      vascular protection and thus reduce recurrence of arterial events in vEDS patients.

      The primary objective of this study is to determine in patients with molecularly proven vEDS,
      whether an Ang II receptor blocker, prescribed at an optimally tolerated dose combined with
      the reference celiprolol treatment, decreases the 24 months rate of both asymptomatic and
      symptomatic cardiovascular (CV) events when compared to placebo.

      Methodology:

      Multicenter, double-blind, randomized (1:1), placebo-controlled, parallel group, study with
      blind endpoint evaluation in adult vEDS patients.

      Main criteria for inclusion:

      Patients of both sexes aged 18 to 70 years with molecularly proven vEDS, not in an acute
      phase of the disease, with no contra-indication for taking an Ang II blocker.
    

Intervention name(s): Irbesartan; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Irbesartan: 150 or 300 mg o.d. The up-titration of irbesartan from 150 mg to 300 mg o.d. occur during the first 8 weeks following randomization; Placebo o.d. to match 150mg or 300mg irbesartan tablets
Intervention MeSH terms: Irbesartan
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Ehlers-Danlos syndrome, vascular type; Type 2 Angiotensin Receptor Blockers