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

• ClinicalTrials.gov Identifier: NCT03066453
• Recruitment Status: Terminated
• First Posted: February 28, 2017
• Last Update Posted: September 5, 2021
• Sponsor: University Hospital, Lille
• Information provided by (Responsible Party): University Hospital, Lille

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: Tobi Inhalant Product; Drug: Nebcin	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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.
• Actual Study Start Date: June 13, 2017
• Actual Primary Completion Date: January 16, 2020
• Actual Study Completion Date: January 16, 2020

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures :

1. Forced expiratory volume at one second (FEV1) by spirometry [ Time Frame: 18 months of the cure ]
   measure of dyspnea

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

France

CRCM pédiatrique - CHU d'Amiens Hôpital Nord

Amiens, France

CRCM mixte - CHU de Caen Hôpital Côte de Nacre

Caen, France

CRCM mixte - CH de Dunkerque

Dunkerque, France

CRCM mixte - CH de Lens

Lens, France

CRCM adulte - CHRU de Lille Hôpital Calmette

Lille, France

CRCM pédiatrique - CHRU de Lille Hôpital Jeanne de Flandres

Lille, France

CRCM mixte - CHU de Rouen Hôpital Charles Nicolle

Rouen, France

Sponsors and Collaborators

University Hospital, Lille

Investigators

• Principal Investigator: Anne Prévotat, MD; University Hospital, Lille

More Information

• Responsible Party: University Hospital, Lille
• ClinicalTrials.gov Identifier: NCT03066453
• Other Study ID Numbers: 2014_21; 2014-003882-10 ( EudraCT Number ); PHRC I 2013 ( Other Identifier: number of funding )
• First Posted: February 28, 2017
• Last Update Posted: September 5, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Lille:

cystic fibrosis, tobramycin, antibiotic courses, FEV1

Additional relevant MeSH terms:

Cystic Fibrosis; Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases