Evaluation of Short Antibiotic Combination Courses Followed by Aerosols in Cystic Fibrosis (TOBRAMUC)

Evaluation of an Antibiotic Treatment With 14 Days of Intravenous Tobramycin Versus the Same Antibiotic Associated With 5 Days of Intravenous Tobramycin Followed by Tobramycin Aerosol for 9 Days in Cystic Fibrosis.

The aim of this study is to investigate the efficacy of antibiotic therapy with any antibiotic (IV) and IV (Nebcin®) tobramycin for 5 days followed by Solution for nebuliser inhalation (Tobi®) for 9 days and antibiotic cures using 14 days of tobramycin IV. In the case of positive results, the reduction of the duration of IV treatment of tobramycin from 14 days to 5 days would limit the risk of toxicity.

Study Overview

• Status: Terminated
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Tobi Inhalant Product; Drug: Nebcin

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Amiens, France
    • CRCM pédiatrique - CHU d'Amiens Hôpital Nord
  • Caen, France
    • CRCM mixte - CHU de Caen Hôpital Côte de Nacre
  • Dunkerque, France
    • CRCM mixte - CH de Dunkerque
  • Lens, France
    • CRCM mixte - CH de Lens
  • Lille, France
    • CRCM adulte - CHRU de Lille Hôpital Calmette
  • Lille, France
    • CRCM pédiatrique - CHRU de Lille Hôpital Jeanne de Flandres
  • Rouen, France
    • CRCM mixte - CHU de Rouen Hôpital Charles Nicolle

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient with cystic fibrosis confirmed by sweat or genetic test
• Patient with clinical signs of exacerbation (increased cough, sputum (abundance, purulence), fever, anorexia, weight loss and FEV1) or acute exacerbations (defined at the clinician's discretion )
• FEV1 ≥ 25%
• Pseudomonas aeruginosa chronic carriers (defined by at least two antipyocyanic precipitation arcs or at least 3 successive positive ECBCs over a period of 18 months)
• Patient who received at least 1 IV course of antibiotics in the 18 months prior to inclusion.

Exclusion Criteria:

• Severe exacerbation (requiring hospitalization due to severe amputation of FEV 1, oxygen deficiency, or severe impairment of general health).
• Patient with 3rd antibiotic therapy (triple therapy)
• Patient colonized in Burkholderia cepacia
• Patient colonized by an atypical mycobacterium

• Patient with pulmonary transplant or transplant

  • chronic tinnitus
  • patient using hearing aid
• Hypersensitivity to tobramycin and other antibiotics of the aminoglycoside family
• Cirrhosis of Grades B and C according to the Child-Pugh Classification
• Myasthenia gravis
• Simultaneous administration of another aminoglycoside
• Renal failure
• Recent history of severe hemoptysis (within 2 months before inclusion)
• Patient participating simultaneously in another clinical study conducted on a drug for the duration of its participation in this research

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard cure; Antibiotic IV (Nebcin) 14 days and 14 days of tobramycin IV associated with one or more other antibiotic (s) IV in routine care	Drug: Tobi Inhalant Product; inhaled tobramycin 300 mg twice per day; Drug: Nebcin; 10 to 12 mg/kg/day in 1 injection for adults and 10 to 15 mg/kg in 1 pediatric injection (combined with another IV antibiotic)
Experimental: Short cure; antibiotic IV (Nebcin)14 days but with only 5 days of tobramycin IV followed 9 days of inhaled tobramycin (Tobi Inhalant Product) associated with one or more other antibiotic (s) IV in routine care	Drug: Tobi Inhalant Product; inhaled tobramycin 300 mg twice per day; Drug: Nebcin; 10 to 12 mg/kg/day in 1 injection for adults and 10 to 15 mg/kg in 1 pediatric injection (combined with another IV antibiotic)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced expiratory volume at one second (FEV1) by spirometry	measure of dyspnea	18 months of the cure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced expiratory volume at one second (FEV1) by spirometry	measure of dyspnea	baseline and between day 16 or day 22
Visual Analog Scale	measure of dyspnea, condition of patient, bronchial congestion	baseline and between day 16 or day 22
number of participants with Bronchial congestion		baseline and between day 16 or day 22
Sputum sample culture	a descriptive analysis of Pseudomonas aeruginosa, and the other bacteria in the bacterial flora of sputum	baseline and between day 16 or day 22
Occurrence of the first exacerbation after the cure		during 18 months
Number of pulmonary exacerbations and those leading to hospitalization		during 18 months

Collaborators and Investigators

• Sponsor: University Hospital, Lille

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2017
• Primary Completion (Actual): January 16, 2020
• Study Completion (Actual): January 16, 2020

Study Registration Dates

• First Submitted: February 23, 2017
• First Submitted That Met QC Criteria: February 27, 2017
• First Posted (Actual): February 28, 2017

Study Record Updates

• Last Update Posted (Actual): September 5, 2021
• Last Update Submitted That Met QC Criteria: August 30, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: cystic fibrosis, tobramycin, antibiotic courses, FEV1
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: 2014_21; 2014-003882-10 (EudraCT Number); PHRC I 2013 (Other Identifier: number of funding)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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