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

Primary Purpose

Chronic Lung Infection With Pseudomonas Aeruginosa in Cystic Fibrosis

Status
Terminated
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
TIS or TIP
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Chronic Lung Infection With Pseudomonas Aeruginosa in Cystic Fibrosis focused on measuring Cystic Fibrosis, Pseudomonas aeruginosa, Lung Clearance Index, Multiple Breath Washout, Inhaled Tobramycin, Inhaled Antibiotics.

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tobramycin ALL

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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.
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.
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.
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
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.

Full Information

First Posted
September 22, 2014
Last Updated
January 2, 2018
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02248922
Brief Title
Evaluation of Lung Clearance Index in Cystic Fibrosis (CF) Patients, Infected With P.Aeruginosa
Acronym
ELIXIR
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Terminated
Why Stopped
Reason for termination was challenge with enrollment and recruitment. A significant decrease in the eligible patient population was main driver.
Study Start Date
January 27, 2015 (Actual)
Primary Completion Date
April 10, 2017 (Actual)
Study Completion Date
April 10, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lung Infection With Pseudomonas Aeruginosa in Cystic Fibrosis
Keywords
Cystic Fibrosis, Pseudomonas aeruginosa, Lung Clearance Index, Multiple Breath Washout, Inhaled Tobramycin, Inhaled Antibiotics.

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tobramycin ALL
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
TIS or TIP
Intervention Description
300mg nebulized Tobramycin (Tobramycin inhalation solution(TIS)) or TOBI Podhaler (Tobramycin inhalation powder(TIP), equivalent dry powder)
Primary Outcome Measure Information:
Title
Change From Baseline in Lung Clearance Index (LCI) After 4 Weeks Following Onset of Study
Description
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.
Time Frame
Baseline, week 4
Secondary Outcome Measure Information:
Title
Change From Baseline of Forced Expiratory Volume at 1 Second (FEV1) After 4 Weeks Following Onset of Study
Description
Change of FEV1 (Forced expiry volume in the first second) measured by Spirometry
Time Frame
Baseline, week 4
Title
Change From Baseline of Colony-forming Units (CFU) After 4 Weeks Following Onset of Study
Description
Microbacterial density of Pseudomonas aeruginosa in Sputum-Samples in CFU (Colony Forming Units) per gram sputum.
Time Frame
Baseline, week 4
Title
Change From Baseline in Lung Clearance Index (LCI) After 1 Week
Description
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.
Time Frame
Baseline, week 1
Title
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)
Description
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.
Time Frame
week 4, week 8
Title
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)
Description
Change of FEV1 (Forced expiry volume in the first second) measured by Spirometry
Time Frame
week 4, week 8
Title
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)
Description
Microbacterial density of Pseudomonas aeruginosa in Sputum-Samples in CFU (Colony Forming Units) per gram sputum.
Time Frame
week 4, week 8

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jörg Ziegler, PhD
Organizational Affiliation
Novartis Pharma GmbH, Nürnberg, Germany
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Novartis Investigative Site
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Novartis Investigative Site
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Novartis Investigative Site
City
Germering
ZIP/Postal Code
82110
Country
Germany
Facility Name
Novartis Investigative Site
City
Jena
ZIP/Postal Code
07740
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing 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
Citations:
PubMed Identifier
32532226
Citation
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.
Results Reference
derived

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

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