Global Registry to Gather Data on Natural History of Patients With Hereditary Angioedema Type I and II (HGR)

The Global Registry on Hereditary Angioedema Type I and II

The objective of this international hereditary angioedema (HAE) register is to collect homogeneous clinical and laboratory data on patients with HAE type I and II gathering better information on the natural course of the disease and detecting therapeutic options to manage it.

Study Overview

• Status: Recruiting
• Conditions: Hereditary Angioedema Type I and II
• Intervention / Treatment: Diagnostic test: functional and antigenic C1 inhibitor

Detailed Description

It is an international multicenter disease registry, the principal investigator at each center is responsible for competent ethic committee/institutional review board approval and for identifying co-investigators, who collect patients' informed consent and insert patients' data. Participating patients own their data. Upon acceptance of the informed consent, the treating physician transfers data of the case report form (CRF) to a specifically designed electronic support (eCRF) and the patients enter data on attacks. Physicians at center fill-in the eCRF with data for demography, diagnosis, prophylaxis and associated diseases. Plasma levels of C1 inhibitor antigen and function and of C4 antigen document laboratory diagnostic criteria. Each patient has a national identifier code. Patients fill-in attack reports that encompass duration, severity and treatment of each angioedema episode. C1 inhibitor coding gene (SERPING1) genotype is entered according to the last Hugo nomenclature. Yearly update of information is recommended, patients with follow up above two years are moved in a separate area and excluded from analysis. Each patient prospectively fills data on attacks. On a specific informed consent, the patient can agree on storing biological material (plasma and nucleic acids) for research purposes.

The data processor is an innovative start-up (Cloud-R s.r.l. Milan, Italy) that manages all data according to a specific contract and in compliance with current regulation on sensitive data security and processing. The Registry, delivered in the mode of Registry-as-a-Service (RaaS), is designed following General Data Protection Regulation (GDPR) guidelines, and issues regular software and infrastructure enhancements as a part of the normal operational mode. The system generates statistics of aggregated anonymized data following the participating centers' hierarchy levels and Global Registry governance rules. Patients supply data on attacks either on paper support or using a Web form or a mobile application. These data will flow into a staging area for physician validation before being considered valid for statistics. For each entry the system updates in real-time all the statistics and dashboards. The platform has configurable functionalities to support data quality management. It provides data format validation, integration to external qualified libraries, alerts, dashboards, automatic index calculations, advanced filters and queries, data change log. This open architecture, allows integration of the system, via standard API's, to external or sub-registries, registries, biobanks and clinical bioinformatics tools, i.e. for specific trial studies leveraging a specific cluster of patients already present in the Global Registry.

An independent non-profit foundation (HGRF) made of representatives of patients' associations is in charge for funding and delegates all the management to the HAE Global Registry Board (HGRB). The HGRB is in charge for operational, assisted by the HAE Global Registry Scientific Committee (HGRSC) for topics of competence. No registry member, center, group or board can access the entire set of data. All registry members, as single or group, can propose studies based on aggregated data by addressing the request to the HGRSC. Analysis and studies of data at local centers can occur at any time. Members of HGRB and HGRSC are elected to be representative of different cultural and geographic backgrounds. Their offices have a two-year term with no more than one consecutive renewal. Angioedema centers can join the Registry upon request to the HGRB . The registry quality control system periodically checks Registry entries and compliance of eCRF with the source data. For each information, the system will grant traceability of time and author.

• Study Type: Observational
• Enrollment (Anticipated): 220

Contacts and Locations

• Study Contact: Name: marco cicardi, MD; Phone Number: +39 0239042516; Email: marco.cicardi@unimi.it

Study Locations

• Italy
  • Milan, Italy, 20157
    • Recruiting
    • ASST FBF Sacco
    • Contact: marco cicardi, M.D.; Phone Number: +3950319829; Email: marco.cicardi@unimi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

patients diagnosed with HAE type I and II and followed by a referral center for angioedema

Description

Inclusion Criteria:

• patients diagnosed with HAE type I and II with signed informed consent
• laboratory diagnostic criteria documenting plasma levels of C1 inhibitor antigen and function and of C4 antigen

Exclusion Criteria:

• patients without HAE type I and II
• patients without documented laboratory diagnostic criteria
• patients not capable to give informed consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
hereditary angioedema type I; Patients were diagnosed as C1 inhibitor HAE type I when functional and antigenic C1 inhibitor were ≤ 50% of normal	Diagnostic test: functional and antigenic C1 inhibitor; Diagnosis of HAE is based on personal and/or family history of angioedema and on C1 inhibitor functional or antigenic plasma levels ≤50% of normal.; Other Names: genetic analysis
hereditary angioedema type II; Patients were diagnosed as type II when functional C1 inhibitor was ≤50% and antigenic was >50% of normal	Diagnostic test: functional and antigenic C1 inhibitor; Diagnosis of HAE is based on personal and/or family history of angioedema and on C1 inhibitor functional or antigenic plasma levels ≤50% of normal.; Other Names: genetic analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of angioedema events	Number of angioedema events	Through study completion, an average of 5 years
Time of angioedema events	Time in hours of presence of angioedema symptoms	Through study completion, an average of 5 years
Severity of angioedema events	Number of severe, moderate, mild angioedema symptoms based on a three point scale patient reported outcome	through study completion, an average of 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comorbidities	Number and type of comorbidities recorded according to the International Classification of Diseases 9 codes	Through study completion , an average of 5 years
Treatment-Emergent comorbidities	Incidence of comorbidities emerging in patients exposed to specific treatments	Through study completion , an average of 5 years
Treatment efficacy	Hours of presence of angioedema symptoms during specific long term prophylaxis	Through study completion , an average of 5 years

Collaborators and Investigators

• Sponsor: HAE Global Registry Foundation
• Investigators: Principal Investigator: marco cicardi, MD, HAE Global Registry Foundation

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2017
• Primary Completion (Anticipated): December 31, 2019
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: January 23, 2019
• First Submitted That Met QC Criteria: January 31, 2019
• First Posted (Actual): February 4, 2019

Study Record Updates

• Last Update Posted (Actual): February 5, 2019
• Last Update Submitted That Met QC Criteria: February 3, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: angioedema; disease registry; C1 inhibitor; anti bradykinin treatments
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Angioedema; Angioedemas, Hereditary; Hereditary Angioedema Types I and II; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Complement C1 Inhibitor Protein
• Other Study ID Numbers: HAERegistry

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All registry members, as single or group, can propose studies based on aggregated anonymized data by addressing the request to the HAE Global Registry Scientific Committee (HGRSC)
• IPD Sharing Time Frame: entire study period
• IPD Sharing Access Criteria: to be a member of the HAERegistry and have the approval of the HGRSC to analyze data
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

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