The Italian REgistry of Pulmonary Non-tuberculous mycobactEria (IRENE)

The Italian Registry of Pulmonary Non-tuberculous Mycobacteria

The Italian registry of pulmonary non-tuberculous mycobacteria (NTM) -IRENE- is an observational, multicenter, prospective, cohort study enrolling consecutive adult patients with either a NTM respiratory infection or NTM-Pulmonary Disease. The coordinating center is located at the Pulmonary Department of the Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. So far, more than 35 centers, including mainly pulmonary and infectious disease departments, joined the registry. The registry has been developed to accept an unlimited number of patients and no deadlines have been decided.

Study Overview

• Status: Recruiting
• Conditions: Nontuberculous Mycobacteria

Detailed Description

The epidemiology of patients suffering from a pulmonary disease due to NTM (NTM-PD), which is characterized by symptomatic, progressive inflammatory lung damage and defined in 2007 in the ATS/IDSA guidelines, still remains unclear. Reporting of NTM-PD to health authorities is often not mandated in several countries and the current estimates have been obtained from sentinel surveillance or laboratory-based studies, retrospective cohort studies, or audits of administrative databases. Until now no data have been published on the epidemiology of respiratory NTM infections in Italy.

The Italian registry of pulmonary NTM (IRENE) is an observational, multicenter, prospective, cohort study enrolling consecutive adult patients with either a NTM respiratory infection or NTM-PD. The coordinating center is located at the Pulmonary Department of the Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. So far, more than 35 centers, including mainly pulmonary and infectious disease departments, joined the registry. The study is sponsored by the Policlinico Hospital in Milan. The study website is located at www.registroirene.it.

Adult (>=18 years) patients with all of the following are included in the registry: 1) at least one positive culture for any NTM species from any respiratory sample; 2) at least one positive culture for NTM isolated in the year prior the enrolment and/or prescribed NTM treatment in the year prior the enrolment; 3) Given consent to inclusion in the study. No exclusion criteria are applied to the study. Patients included in the registry are mainly recruited among pulmonary and ID out- and in-patient services. Adult cystic fibrosis, lung transplant, and tuberculosis clinics represent other recruitment centers. The registry has been developed to accept an unlimited number of patients and no deadlines have been decided.

Patients are managed according to standard operating procedures implemented in each IRENE clinical center without any interference from the study team. A baseline case report form is collected at patient's enrolment including demographics, comorbidities, microbiological, laboratory, functional, radiological, clinical, and treatment data. Then, study investigators enter follow-up data on an annual basis.

An IRENE biobank has also been developed within the network and linked to the clinical data of the registry. IRENE sites can collect samples, including blood, serum, plasma, respiratory specimens (sputum, induced sputum, tracheal aspirate, or bronchoalveolar lavage), urine, and NTM isolates at the first visit and during follow up on a voluntary basis.

• Study Type: Observational
• Enrollment (Anticipated): 500

Contacts and Locations

• Study Contact: Name: Stefano Aliberti, MD; Phone Number: +390250320627; Email: stefano.aliberti@unimi.it

Study Locations

• Italy
  • Bologna, Italy
    • Not yet recruiting
    • Malattie Infettive, Alma Mater Studiorum Università di Bologna
  • Bologna, Italy
    • Not yet recruiting
    • Pneumologia, Alma Mater Studiorum Università di Bologna
    • Contact: Stefano Nava, MD; Email: stefano.nava@aosp.bo.it
  • Brescia, Italy
    • Not yet recruiting
    • Clinica di Malattie Infettive e Malattie Tropicali, Spedali Civili di Brescia, Università di Brescia
    • Contact: Alberto Matteelli, MD; Email: matteelli@med.unibs.it
  • Catania, Italy
    • Not yet recruiting
    • Malattie Infettive, Ospedale Garibaldi-NESIMA di Catania
    • Contact: Salvatore Tosto, MD; Email: salvotosto56@yahoo.it
  • Cosenza, Italy
    • Not yet recruiting
    • U.O.C. Malattie Infettive, Azienda Ospedaliera di Cosenza
    • Contact: Antonio Mastroianni, MD; Email: antoniomastroianni@yahoo.it
  • Ferrara, Italy
    • Not yet recruiting
    • Pneumologia, Azienda Ospedaliero-Universitaria di Ferrara
    • Contact: Marco Contoli, MD; Email: marco.contoli@unife.it
  • Firenze, Italy
    • Not yet recruiting
    • Dipartimento Medicina Sperimentale e Clinica, SOD Malattie Infettive e Tropicali, Azienda Ospedaliero Universitaria Careggi
    • Contact: Filippo Bartalesi, MD; Email: bartalesif@aou-careggi.toscana.it
  • Genova, Italy
    • Not yet recruiting
    • Malattie Infettive, IRCCS-AOU San Martino
    • Contact: Antonio Di Biagio, MD; Email: adibiagioa@gmail.com
  • Milan, Italy, 20122
    • Recruiting
    • Department of Pathophysiology and Transplantation, University of Milan Internal Medicine Department, Respiratory Unit and Cystic Fibrosis Adult Center Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
    • Contact: Stefano Aliberti, MD; Phone Number: +390250320627; Email: stefano.aliberti@unimi.it
  • Milan, Italy
    • Not yet recruiting
    • Malattie Infettive, Ospedale Luigi Sacco
    • Contact: Fabio Franzetti, MD; Email: fabio.franzetti@unimi.it
  • Milan, Italy
    • Not yet recruiting
    • Pneumologia, Ospedale Luigi Sacco
    • Contact: Pierachille Santus, PhD; Email: pierachille.santus@unimi.it
  • Milan, Italy
    • Not yet recruiting
    • Regional TB Reference Centre, Istituto Villa Marelli, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
    • Contact: Luigi Ruffo Codecasa, MD; Phone Number: +390264445833; Email: luigiruffo.codecasa@ospedaleniguarda.it
  • Modena, Italy
    • Not yet recruiting
    • Malattie Infettive, Ospedale di Modena
    • Contact: Cristina Mussini, MD; Email: cristina.mussini@unimore.it
  • Modena, Italy
    • Not yet recruiting
    • Pneumologia, Ospedale di Modena
    • Contact: Fabrizio Luppi, MD; Email: fabrizio.luppi@unimore.it
  • Pavia, Italy
    • Not yet recruiting
    • Pneumologia, Fondazione IRCCS Policlinico San Matteo
    • Contact: Angelo Corsico, MD; Email: corsico@unipv.it
  • Pisa, Italy
    • Not yet recruiting
    • Pneumologia, Ospedale di Pisa
    • Contact: Pierluigi Paggiaro, MD; Email: pierluigi.paggiaro@unipi.it
  • Pistoia, Italy
    • Not yet recruiting
    • S.O.C. Malattie Infettive II, AUSL Toscana Centro - Pistoia, Ospedale San Jacopo
    • Contact: Michele Trezzi, MD; Email: michele.trezzi@gmail.com
  • Roma, Italy
    • Not yet recruiting
    • Pneumologia, Policlinico Gemelli
    • Contact: Luca Richeldi, MD; Email: luca.richeldi@policlinicogemelli.it
  • Roma, Italy
    • Not yet recruiting
    • UOC di Medicina Interna e Disfunzioni Respiratorie, Azienda Universitaria Ospedaliera Policlinico Umberto I di Roma
    • Contact: Paolo Palange, MD; Email: paolo.palange@uniroma1.it
  • Roma, Italy
    • Not yet recruiting
    • UOS Day Service Malattia Tubercolare afferente all'UOC Malattie Infettive dell'Apparato Respiratorio, Istituto Nazionale per le Malattie Infettive "L. Spallanzani" - IRCCS
    • Contact: Gina Gualano, MD; Email: gina.gualano@inmi.it
  • Sassari, Italy
    • Not yet recruiting
    • Pneumologia, Dipartimento Di Medicina Clinica e Sperimentale, Università degli studi di Sassari
    • Contact: Pietro Pirina, MD; Email: pirina@uniss.it
  • Torino, Italy
    • Not yet recruiting
    • Divisione di Pneumologia, AOU Città della Salute e della Scienza di Torino, Molinette
    • Contact: Paolo Solidoro, MD; Email: psolidoro@cittadellasalute.to.it
  • Torino, Italy
    • Not yet recruiting
    • Malattie Infettive, Università degli studi di Torino
    • Contact: Andrea Calcagno, MD; Email: andrea.calcagno@unito.it
  • Treviso, Italy
    • Not yet recruiting
    • UO di Pneumotisiologia, Ospedale di Vittorio Veneto
    • Contact: Stefano Nardini, MD; Email: snardini.pneumologo@gmail.com
  • Trieste, Italy
    • Not yet recruiting
    • Dipartimento di Pneumologia, Ospedale Universitario di Cattinara
    • Contact: Marco Confalonieri, MD; Email: marco.confalonieri@aots.sanita.fvg.it
  • Monza Brianza
    • Monza, Monza Brianza, Italy
      • Not yet recruiting
      • Clinic of Infectious Diseases, 'San Gerardo" Hospital-ASST Monza, University Milano-Bicocca, Milano
      • Contact: Andrea Gori, MD; Email: andrea.gori@unimib.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients included in the registry are mainly recruited among pulmonary and Infectious diseases out- and in-patient services. Adult cystic fibrosis, lung transplant, and tuberculosis clinics represent other recruitment centers. A heterogeneous population of patients with NTM infection/NTM-Pulmonary Disease sharing different clinical phenotypes is expected to be enrolled in the registry. IRENE has a special focus on four patients' categories: 1) immunocompetent/bronchiectatic, 2) HIV-positive, 3) cystic fibrosis and 4) lung transplanted patients.

Description

Inclusion Criteria (all of them):

• Adult (>=18 years) patients
• At least one positive culture for any NTM species from any respiratory sample
• At least one positive culture for NTM isolated in the year prior the enrolment and/or prescribed NTM treatment in the year prior the enrollment
• Given consent to inclusion in the study.

Exclusion Criteria:

No exclusion criteria are applied to the study

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
Proportion of patients meeting the quality standards for NTM-PD care suggested by international guidelines (including the latest ERS 2017 guidelines)	The number of patients with NTM-PD who have been managed or treated according to the recommendations published by international guidelines	5 years

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
• Collaborators: Fondazione Policlinico Universitario Agostino Gemelli IRCCS; IRCCS Azienda Ospedaliero-Universitaria di Bologna; Azienda Ospedaliero, Universitaria Pisana; Università degli Studi di Ferrara; Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia; Niguarda Hospital; University of Turin, Italy; ASST Fatebenefratelli Sacco; Azienda Ospedaliero-Universitaria di Modena; IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy; Azienda Ospedaliera Universitaria Policlinico "G. Martino"; Azienda Ospedaliero-Universitaria Careggi; Azienda Ospedaliera San Gerardo di Monza; Azienda Policlinico Umberto I; Fondazione IRCCS Policlinico San Matteo di Pavia; A.O.U. Città della Salute e della Scienza - Molinette Hospital; Azienda Unità Locale Socio Sanitaria n.9 Treviso; Ospedale Maggiore Di Trieste; Ospedale San Jacopo, Pistoia, Italy; Istituto Nazionale per le Malattie Infettive Spallanzani, Roma; Policlinico Universitario, Catania; Azienda Ospedaliera Cosenza; Azienda Ospedaliero Universitaria di Sassari
• Investigators: Study Director: Stefano Aliberti, MD, Department of Pathophysiology and Transplantation, University of Milan Internal Medicine Department, Respiratory Unit and Cystic Fibrosis Adult Center Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Study Chair: Francesco Blasi, MD, Department of Pathophysiology and Transplantation, University of Milan Internal Medicine Department, Respiratory Unit and Cystic Fibrosis Adult Center Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Study Chair: Luigi Ruffo Codecasa, MD, Regional TB Reference Centre, Istituto Villa Marelli, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; Study Chair: Andrea Gori, MD, Clinic of Infectious Diseases, 'San Gerardo" Hospital-ASST Monza, University Milano-Bicocca, Milano, Italy

Publications and helpful links

General Publications

• Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, Gordin F, Holland SM, Horsburgh R, Huitt G, Iademarco MF, Iseman M, Olivier K, Ruoss S, von Reyn CF, Wallace RJ Jr, Winthrop K; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007 Feb 15;175(4):367-416. doi: 10.1164/rccm.200604-571ST. No abstract available. Erratum In: Am J Respir Crit Care Med. 2007 Apr 1;175(7):744-5. Dosage error in article text.
• Haworth CS, Banks J, Capstick T, Fisher AJ, Gorsuch T, Laurenson IF, Leitch A, Loebinger MR, Milburn HJ, Nightingale M, Ormerod P, Shingadia D, Smith D, Whitehead N, Wilson R, Floto RA. British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD). Thorax. 2017 Nov;72(Suppl 2):ii1-ii64. doi: 10.1136/thoraxjnl-2017-210927. No abstract available.
• Faverio P, Stainer A, Bonaiti G, Zucchetti SC, Simonetta E, Lapadula G, Marruchella A, Gori A, Blasi F, Codecasa L, Pesci A, Chalmers JD, Loebinger MR, Aliberti S. Characterizing Non-Tuberculous Mycobacteria Infection in Bronchiectasis. Int J Mol Sci. 2016 Nov 16;17(11):1913. doi: 10.3390/ijms17111913.
• Bonaiti G, Pesci A, Marruchella A, Lapadula G, Gori A, Aliberti S. Nontuberculous Mycobacteria in Noncystic Fibrosis Bronchiectasis. Biomed Res Int. 2015;2015:197950. doi: 10.1155/2015/197950. Epub 2015 May 27.
• Floto RA, Olivier KN, Saiman L, Daley CL, Herrmann JL, Nick JA, Noone PG, Bilton D, Corris P, Gibson RL, Hempstead SE, Koetz K, Sabadosa KA, Sermet-Gaudelus I, Smyth AR, van Ingen J, Wallace RJ, Winthrop KL, Marshall BC, Haworth CS; US Cystic Fibrosis Foundation and European Cystic Fibrosis Society. US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis. Thorax. 2016 Jan;71 Suppl 1(Suppl 1):i1-22. doi: 10.1136/thoraxjnl-2015-207360.
• Aliberti S, Codecasa LR, Gori A, Sotgiu G, Spotti M, Di Biagio A, Calcagno A, Nardini S, Assael BM, Tortoli E, Besozzi G, Ferrarese M, Matteelli A, Girardi E, De Lorenzo S, Seia M, Gramegna A, Del Prato B, Terranova L, Oriano M, Sverzellati N, Mirsaeidi M, Chalmers JD, Haworth CS, Loebinger MR, Aksamit T, Winthrop K, Ringshausen FC, Previdi G, Blasi F; IRENE Network. The Italian registry of pulmonary non-tuberculous mycobacteria - IRENE: the study protocol. Multidiscip Respir Med. 2018 Aug 9;13(Suppl 1):33. doi: 10.1186/s40248-018-0141-8. eCollection 2018.

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2017
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: October 22, 2017
• First Submitted That Met QC Criteria: November 7, 2017
• First Posted (Actual): November 13, 2017

Study Record Updates

• Last Update Posted (Actual): March 26, 2018
• Last Update Submitted That Met QC Criteria: March 22, 2018
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: MAC; Nontuberculous Mycobacteria; Non-tuberculous mycobacteria; NTM-PD; NTM-LD; M. avium; M. intracellulare; M. abscessus; Atypical mycobacteria; NTM
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections
• Other Study ID Numbers: IRENE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IRENE is the official Italian network within the EMBARC European NTM registry. All Italian patients included in the European NTM registry will be enrolled through IRENE and IRENE data will be incorporated into the European NTM registry.
• IPD Sharing Time Frame: 2018-2023
• IPD Sharing Access Criteria: All the patients' data
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

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