Trikafta/Kaftrio and Pseudomonas Aeruginosa

NCT05675592 | Unknown

• 2 other identifiers: 173/INT/2021FFC#16/2021
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this observational study o is to define whether, how and to what extent treatment with Trikafta/Kaftrio directly affects Pseudomonas aeruginosa in individuals with cystic fibrosis. The main questions it aims to answer are:

• whether Trikafta/Kaftrio affects the bacterial phenotypes and susceptibility to antibiotics;
• whether Trikafta/Kaftrio impacts the bacterial virulence. Participants will be asked the permission to store and analyze P. aeruginosa isolates collected from respiratory samples for usual care plans before the initiation of treatment with Trikafta/Kaftrio and after 12 and 18 months of treatment. The results of bacterial analysis will be matched with clinical data at the specific time-points. We expect to define effects of Trikafta/Kaftrio on P. aeruginosa and identify bacterial phenotypes as possible risk factors for its efficacy.

Conditions

Cystic Fibrosis

Keywords

Trikafta; Pseudomonas aeruginosa; susceptibility to antibiotics; bacterial phenotype; bacterial transcriptome; bacterial genome; bacterial virulence

Outcome Measures

Primary Outcomes (2)

• bacterial phenotypes

  motility by pilus, motility by flagellum, secretion of proteases, secretion of pyocyanin of P. aeruginosa strains isolated at T0 and clonal ones isolated at T12m and T18m post treatment with Trikafta/Kaftrio

  0-18 months

• respiratory function

  respiratory function, evaluated as FEV1 (%), measured at time at T0, T12m and T18m post Trikafta/Kaftrio treatment

  0-18 months

Secondary Outcomes (5)

• susceptibility to antibiotics

  0-18 months

• mucoidy

  0-18 months

• expression profile

  0-18 months

• genetic variants

  0-18 months

• impact on CFTR

  0-18 months

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

20 patients with CF (from IRCCS Ca' Granda Foundation, Ospedale Maggiore Policlinico, Milan; IRCCS Pediatrico Bambino Gesù, Rome) will be enrolled. Currently, some patients already started treatment with Kaftrio and P. aeruginosa strains have been recovered for other studies. Of these patients, we will include only those for whom clonal strains at T0, T12m and T18m will be identified. If the number of retrospective patients is sufficient, no other patients will be recruited prospectively. Once enrolled, patients may drop out of the study if: 1. they are unable to expectorate at T12m and T18m; 2. the sputum is negative for P. aeruginosa at T12m or T18m; 3. none of the P. aeruginosa strains isolated at T12m and T18m is clonal to at least one strain isolated at T0. If the dropout is higher than expected, recruitment will continue until the necessary number of samples to be analyzed is obtained.

You may qualify if:

• Definite diagnosis of CF and regular follow up, in accordance with the standard operating procedures in force at the Centres
• Homozygous for the F508del mutation (F508del/F508del) in the CFTR gene or heterozygous for the F508del mutation and with a minimal function mutation in the other allele (F508del/minimum function mutation)
• Chronically infected with P. aeruginosa (defined as having at least 50% or more sputum cultures positive for P. aeruginosa in the previous year)
• Candidates starting treatment with Kaftrio or being treated with Kaftrio (retrospective phase)
• Both sexes aged \>12 years
• Obtaining informed consent from patients and/or from patients' parents (according to the modalities foreseen by the protocol)

You may not qualify if:

• Patients unable to understand the instructions and information provided and to be able to adequately accept the modalities of the study.
• Patients unable to expectorate.
• Patients with negative sputum for P. aeruginosa at T0, which in the case of prospective patients corresponds to the time of enrollment.

Sponsors & Collaborators

• Ospedale San Raffaele: lead
• Ospedale Pediatrico Bambin Gesù: collaborator
• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: collaborator

Study Sites (2)

UOC Pediatria Fibrosi Cistica, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Milan, 20132, Italy

RECRUITING

UOC Fibrosi Cistica, IRCCS Ospedale Pediatrico Bambino Gesù

Rome, 00165, Italy

RECRUITING

Related Links

• project behind this study

Biospecimen

Retention: SAMPLES WITHOUT DNA

Pseudomonas aeruginosa strains

MeSH Terms

Conditions

Cystic Fibrosis; Pseudomonas Infections

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Central Study Contacts

Cristina Cigana, PhD

CONTACT

+390226434138; cigana.cristina@hsr.it

Alessandra Bragonzi, PhD

CONTACT

+390226434138; bragonzi.alessandra@hsr.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Associate - Principal Investigator

Study Record Dates

• First Submitted: December 28, 2022
• First Posted: January 9, 2023
• Study Start: February 22, 2022
• Primary Completion: November 16, 2023
• Study Completion: May 16, 2025
• Last Updated: January 11, 2023

Record last verified: 2023-01

Locations

IT (2)