Bradykinin-degradating Enzymes Activities in Angiotensin-Converting Enzyme Inhibitors-associated Angioedema

Condition(s) studied

Investigational drug(s) / intervention(s)

Assay of Bradykinin-degradating enzymes.: Aminopeptidase P activity assay; Dipeptidyl peptidase IV activity assay; Angiotensin Converting Enzyme activity assay; MME gene polymorphisme exploration.

Study summary

Angiotensin-Converting-Enzyme-inhibitors-dependent angioedema (ACEi-AE) is the most frequent form of bradykinin-mediated AE, with an estimated prevalence of 0.1% to 0.7%.

These AE can be explained by the accumulation of bradykinin (BK), a peptide responsible for increase of vascular permeability: ACE inhibitors block ACE, the main inactivation pathway of the BK, thus extending its half-life.

In spite of the the stopping of the drug, systematically performed in the case of ACEi-AE, up to 50% of patients relapsed within 6 months, with maximum risk in the first month after stopping. In addition, the discontinuation of these drugs represents a loss of chance for some patients, without clearly established mastocytic (or histaminic) or bradykinic etiology.

At present there is no method to predict the risk of crisis recurrence in patients who have developed AE-IEC.

The investigators hypothesize that the risk of relapse is associated with a decrease in the activity of BK degradation enzymes (including aminopeptidase P (APP), dipeptidyl peptidase-4 (DPP4), and ECA) that persists at the cessation of IEC.

Eligibility

Primary outcome measure(s)

• Prognostic Value of Bradykinin degradating enzymes — Association between the activity of kinin-degrading enzymes (ECA, APP, DPP4) measured by enzyme methods, expressed in tertiles, and relapse at 6 months.
  The primary outcome is to determine the dynamic prognostic value of each of the kinin catabolism enzyme activities, as biomarkers of the risk of relapse at 6 months in patients with BK-AE associated with ACEi.

Trial sites (4)

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