Evaluation of Lung Clearance Index in Cystic Fibrosis (CF) Patients, Infected With P.Aeruginosa (ELIXIR)

An 8 Week Open-label Interventional Multicenter Study to Evaluate the Lung Clearance Index as Endpoint for Clinical Trials in Cystic Fibrosis Patients ≥ 6 Years of Age, Chronically Infected With Pseudomonas Aeruginosa

The purpose of the study was to evaluate lung clearance index (LCI) by a standardized procedure in a well characterized study setting and to assess feasibility of LCI as a more sensitive method than forced expiratory volume at 1 second (FEV1) to measure effectiveness of antibiotic therapy in patients with CF aged 6 years and older with mild to moderate lung disease.

Study Overview

• Status: Terminated
• Conditions: Chronic Lung Infection With Pseudomonas Aeruginosa in Cystic Fibrosis
• Intervention / Treatment: Drug: TIS or TIP

Detailed Description

This study was terminated prematurely. The reason for trial termination was challenge with enrollment and patient recruitment. A significant decrease in the eligible patient population had been identified as main driver.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Erlangen, Germany, 91054
    • Novartis Investigative Site
  • Essen, Germany, 45147
    • Novartis Investigative Site
  • Frankfurt, Germany, 60590
    • Novartis Investigative Site
  • Germering, Germany, 82110
    • Novartis Investigative Site
  • Jena, Germany, 07740
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed diagnosis of CF
• Patients with elevated LCI of ≥ 7.5 at screening
• Patients with FEV1 of ≥ 50% predicted at screening
• Use of inhaled Tobramycin in a 28 days on / off regimen in the past 3 months before screening
• chronic lung Infection with Pseudomonas aeruginosa

Exclusion Criteria:

• Patients who are regularly receiving more than one class of inhaled anti-pseudomonal antibiotic
• Patients who have used oral or intravenous anti-pseudomonal antibiotics within 28 days prior to on-phase of study drug
• Pregnant or nursing (lactating) women
• Change in dose, formulation or strength of the study drug in the past treatment cycle before screening
• History of hearing loss or chronic tinnitus
• Infection with Burkholderia cenocepacia complex

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Tobramycin ALL; 300mg nebulized Tobramycin (Tobramycin inhalation solution(TIS)) or TOBI Podhaler (Tobramycin inhalation powder(TIP), equivalent dry powder)twice a day (BID) 28days on / 28 days off	Drug: TIS or TIP; 300mg nebulized Tobramycin (Tobramycin inhalation solution(TIS)) or TOBI Podhaler (Tobramycin inhalation powder(TIP), equivalent dry powder)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Lung Clearance Index (LCI) After 4 Weeks Following Onset of Study	The Lung Clearance Index (LCI), measured by Multiple Breath Washout of a tracer gas reflects the obstruction of airways in the lung. Wash-out was completed by definition at the time point when the inhaled gas concentration declined to 2.5% of its concentration at baseline. Washout took longer in patients with more severe disease as gas was trapped in narrowed airways (leading to a higher LCI). A LCI of 7.5 and below is normal.	Baseline, week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline of Forced Expiratory Volume at 1 Second (FEV1) After 4 Weeks Following Onset of Study	Change of FEV1 (Forced expiry volume in the first second) measured by Spirometry	Baseline, week 4
Change From Baseline of Colony-forming Units (CFU) After 4 Weeks Following Onset of Study	Microbacterial density of Pseudomonas aeruginosa in Sputum-Samples in CFU (Colony Forming Units) per gram sputum.	Baseline, week 4
Change From Baseline in Lung Clearance Index (LCI) After 1 Week	The Lung Clearance Index (LCI), measured by Multiple Breath Washout of a tracer gas reflects the obstruction of airways in the lung. Wash-out was completed by definition at the time point when the inhaled gas concentration declined to 2.5% of its concentration at baseline. Washout took longer in patients with more severe disease as gas was trapped in narrowed airways (leading to a higher LCI). A LCI of 7.5 and below is normal.	Baseline, week 1
Change of Lung Clearance Index (LCI) Between Week 4 (End of Study Drug Inhalation in the Current Treatment Cycle) and Week 8 (Prior to Start of Study Drug Inhalation in the Following Treatment Cycle)	The Lung Clearance Index (LCI), measured by Multiple Breath Washout of a tracer gas reflects the obstruction of airways in the lung. Wash-out was completed by definition at the time point when the inhaled gas concentration declined to 2.5% of its concentration at baseline. Washout took longer in patients with more severe disease as gas was trapped in narrowed airways (leading to a higher LCI). A LCI of 7.5 and below is normal.	week 4, week 8
Change of Forced Expiratory Volume at 1 Second(FEV1) Between Week 4 (End of Study Drug Inhalation in the Current Treatment Cycle) and Week 8 (Prior to Start of Study Drug Inhalation in the Following Treatment Cycle)	Change of FEV1 (Forced expiry volume in the first second) measured by Spirometry	week 4, week 8
Change of Colony-forming Units (CFU) Between Week 4 (End of Study Drug Inhalation in the Current Treatment Cycle) and Week 8 (Prior to Start of Study Drug Inhalation in the Following Treatment Cycle)	Microbacterial density of Pseudomonas aeruginosa in Sputum-Samples in CFU (Colony Forming Units) per gram sputum.	week 4, week 8

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Jörg Ziegler, PhD, Novartis Pharma GmbH, Nürnberg, Germany

Publications and helpful links

General Publications

• Sutharsan S, Naehrig S, Mellies U, Sieder C, Ziegler J. An 8 week open-label interventional multicenter study to explore the lung clearance index as endpoint for clinical trials in cystic fibrosis patients >/=8 years of age, chronically infected with Pseudomonas aeruginosa. BMC Pulm Med. 2020 Jun 12;20(1):167. doi: 10.1186/s12890-020-01201-y.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 27, 2015
• Primary Completion (ACTUAL): April 10, 2017
• Study Completion (ACTUAL): April 10, 2017

Study Registration Dates

• First Submitted: September 22, 2014
• First Submitted That Met QC Criteria: September 22, 2014
• First Posted (ESTIMATE): September 25, 2014

Study Record Updates

• Last Update Posted (ACTUAL): October 9, 2018
• Last Update Submitted That Met QC Criteria: January 2, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Cystic Fibrosis, Pseudomonas aeruginosa, Lung Clearance Index, Multiple Breath Washout, Inhaled Tobramycin, Inhaled Antibiotics.
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Pseudomonas Infections
• Other Study ID Numbers: CTBM100CDE02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

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