TerminatedPhase 2ACTRN12620000531910

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..

A Phase IIb, Single-Centre, Randomised, Double-Blind, Comparator-Controlled, Parallel-Group, Pilot Study to evaluate the safety and tolerability of CaEDTA added to Inhaled Tobramycin vs Tobramycin Alone as Adjunctive therapy to a Course of Standard Treatment for Cystic Fibrosis patients Admitted to Hospital with a Pseudomonas aeruginosa Pulmonary Exacerbation.

Sponsor

Telethon Kids Institute

Enrollment

32 participants

Start Date

Mar 6, 2014

Study Type

Interventional

Conditions

Pseudomonas aeruginosa

Summary

Airway iron level has been shown to be raised in patients with cystic fibrosis. Pseudomonas aeruginosa has been shown to have an absolute requirement for iron. We hypothesised that removing excess iron using chelating agents such as ethylene diamine tetra-acetate (EDTA) would improve the bacterial killing ability of antibiotics. We conducted a double-blind, randomised controlled trial to study the safety and efficacy of combining inhaled CaEDTA and tobramycin in cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection undergoing treatment for pulmonary exacerbation.

Eligibility

Sex: Both males and femalesMin Age: 6 Yearss

Inclusion Criteria8

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 Criteria6

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)

Interested in this trial?

Get notified about updates and connect with the research team.

Interventions

We tested if disrupting iron utilisation by Pseudomonas aeruginosa by adding the chelating agent, calcium salt of Ethylene diamine-tetraacetate (CaEDTA) to nebulised tobramycin would enhance bacterial clearance and improve clinical outcomes in cystic fibrosis patients. Study drug: The study drug (active drug or placebo) was supplied in blinded 1·5 ml prefilled syringes which when added to 250 mg tobramycin (Tobra-Day®) resulted in a 4 ml solution at pH 7·1. The active drug consisted of CaEDTA (75mg, 50mM final concentration) in Tris buffered solution, while the placebo consisted of Tris buffered saline. Study design: All patients received standard treatment of their pulmonary exacerbation as per their treating physician. In addition, patients were randomised 1:1 to receive either active drug or placebo. First dose of the study drug was given within the first 72 hours of initiation of intravenous antibiotics. The study consisted of three phases: (i) The inpatient phase for first 2 weeks (while on intravenous antibiotics) when participants received study drug (active drug or placebo) four times daily – twice combined with 250 mg inhaled tobramycin, and twice with 0·9% normal saline; (ii) the 2-6 week outpatient phase during which the participants received study drug twice daily with 250 mg inhaled tobramycin. (iii) The safety phase between 6-10 weeks, when no study drug was given.