Bradykinin-degradating Enzymes Activities in Angiotensin-Converting Enzyme Inhibitors-associated Angioedema (KIN-ACE)

Prognostic Value of the Bradykinin-degradating Enzymes Activities on the Relapse Risk of Angiotensin-Converting Enzyme Inhibitors-associated Angioedema

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.

Study Overview

• Status: Recruiting
• Conditions: Angio-Oedema Caused by Angiotensin-Converting-Enzyme Inhibitor
• Intervention / Treatment: Other: Assay of Bradykinin-degradating enzymes.

• Study Type: Observational
• Enrollment (Estimated): 243

Contacts and Locations

• Study Contact: Name: Federica DEFENDI, PhD; Phone Number: +33(0)0476765416; Email: fdefendi@chu-grenoble.fr

Study Locations

• France
  • Grenoble, France, 38043
    • Recruiting
    • CHU Grenoble Alpes
    • Contact: Fédérica DEFENDI; Phone Number: 33 (0)4 76 76 54 16; Email: fdefendi@chu-grenoble.fr
    • Principal Investigator: Fédérica DEFENDI, PH
  • Lille, France, 59037
    • Recruiting
    • CHRU de Lille _Hôpital Claude-Huriez
    • Contact: David LAUNAY; Email: david.launay@univ-lille.fr
  • Paris, France, 75571
    • Recruiting
    • AP-HP _St Antoine
    • Contact: Olivier FAIN; Email: olivier.fain@aphp.fr
  • Rouen, France, 76 031
    • Recruiting
    • CHU de Rouen
    • Contact: Sébastien MIRANDA; Email: Sebastien.Miranda@chu-rouen.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with Angioedema secondary to Angiotensin Converting Enzyme Inhibitors

Description

Inclusion Criteria:

• Men and women at least 18 years old
• Presenting AE secondary to treatment with Angiotensin Conversion Enzyme Inhibitors for less than 15 days, or an isolated AE (without superficial hives), which lasts at least 15 hours, and whose diagnosis is validated by the expert committee,
• Having signed informed and written consent
• And being affiliated with social security

Exclusion Criteria:

• Patient who had one or more AEs prior to IEC
• Hereditary or acquired deficiency of C1 inhibitor
• Subject with known mutation of the F12 or PLG gene Subject in times of exclusion from another research involving the human person type 1 or 2 Persons referred to in sections L1121-5 to L1121-8 of the public health code (pregnant woman, breastfeeding mother, person deprived of liberty, person subject to legal protection) subject that cannot be contacted in an emergency situation

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prognostic Value of Bradykinin degradating enzymes	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.	Association between the activity of kinin-degrading enzymes (ECA, APP, DPP4) measured by enzyme methods, expressed in tertiles, and relapse at 6 months.

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble
• Collaborators: University Hospital, Rouen; University Hospital, Paris
• Investigators: Principal Investigator: Federica DEFENDI, University Hospital, Grenoble

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2021
• Primary Completion (Estimated): April 26, 2025
• Study Completion (Estimated): April 26, 2025

Study Registration Dates

• First Submitted: February 16, 2021
• First Submitted That Met QC Criteria: February 16, 2021
• First Posted (Actual): February 21, 2021

Study Record Updates

• Last Update Posted (Actual): October 18, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Angioedema; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Protease Inhibitors; Cysteine Proteinase Inhibitors; Bradykinin; Kininogens
• Other Study ID Numbers: 38RC19.025; 2020-A00775-34 (Other Identifier: ID RCB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No