Effect of adding calcium salt of ethylene diamine tetra-acetate (CaEDTA) to nebulised tobramycin on bacterial clearance and lung function in patients with cystic fibrosis with chronic Pseudomonas aeruginosa lung infections: a randomised controlled trial..

Phase 2

• Conditions: Cystic fibrosis; Pseudomonas aeruginosa; Respiratory - Other respiratory disorders / diseases; Human Genetics and Inherited Disorders - Cystic fibrosis; Infection - Other infectious diseases

• Registration Number: ACTRN12620000531910
• Lead Sponsor: Telethon Kids Institute

Brief Summary

Research question: The purpose of our study is to determine if nebulisation of calcium salt of ethylene diamine tetra-acetate (Ca-EDTA) is safe and if it would improve bacterial killing by antibiotics such as tobramycin. Background: Pseudomonas aeruginosa lung infection is a leading cause of morbidity and mortality in cystic fibrosis (CF). Pseudomonas needs iron for its growth and survival. In the CF lung there is increased iron compared to non CF lungs. The Ca-EDTA is a chelating agent that can bind to iron. In our study patients were randomly assigned to receive either 75 mg CaEDTA in Tris buffered saline or placebo (Tris-buffered saline) nebulised in combination with 250 mg tobramycin twice daily for six weeks (two additional doses in first 2 weeks) followed with four week safety follow-up. Participant characteristics: The study is conducted in patients with cystic fibrosis above the age of six years with chronic pseudomonas lung infection admitted to hospital for exacerbation of their lung disease. Key results: Safety of CaEDTA is assessed by clinical assessment, measurement of lung function and blood tests before the study drug and at 2 weeks, 6 weeks and 10 weeks after commencing study drug. Efficacy is measured by comparing the difference in results of sputum load of pseudomonas before and after treatment with CaEDTA added to inhaled Tobramycin (the active agent) relative to placebo. Limitations: Proof of concept study rather than conclusive study.

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Completion: 2016-02-03
• Study Start: 2020-04-30
• Last Update Posted: 4 May 2020

Recruitment & Eligibility

• Status: Stopped early
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

•Male or female 6 years of age or older with a documented diagnosis of CF (positive sweat chloride test, genotype with two identifiable CF mutations) accompanied by one or more clinical features consistent with the CF phenotype.
•Current pulmonary exacerbation requiring antibiotic therapy.
•If older than 6 years, must be able to perform acceptable spirometric manoeuvres.
•FEV1 > 25% of predicted values (if older than 6 years of age).
•Positive sputum or bronchoalveolar lavage culture for Pseudomonas aeruginosa in the past 12 months.
•Must be able to give informed consent or have legally acceptable representative who can give informed consent in accordance with ICH/GCP.
•Females of child-bearing potential must agree to use an acceptable method of contraception for the duration of the trial.

Initially the study was planned to be conducted in children with cystic fibrosis, however due to slow recruitment, the study was extended to include adults with cystic fibrosis with all procedures remaining the same. We therefore obtained additional approval for inclusion of Sir Charles Gairdener Hospital adult patients to the study.

Exclusion Criteria

•Known hypersensitivity to the investigational product or its components or known relevant medication allergy.
•Participation in another study with an investigational drug within 2 months of the planned first dose of investigational product.
•Known relevant substance abuse.
•Female patients who are pregnant or lactating
•Clinically significant disease or other medical condition other than CF or CF related conditions that would, in the opinion or the Investigator, compromise the safety of the patient or quality of the data.
Please note: The presence of additional bacterial or fungal organisms on sputum culture and/or the prescription of additional antibiotics (oral, intravenous, anti-pseudomonal, or non-anti-pseudomonal) at any stage through the trial will NOT affect inclusion into the trial)

Study & Design

• Study Type: Interventional
• Study Design: Not specified