Testing the Effect of Adding Chronic Oral Azithromycin to Inhaled Tobramycin in People With Cystic Fibrosis (CF)

NCT ID: NCT02677701

Last Updated: 2021-06-28

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

119 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-10-21

Study Completion Date

2020-02-13

Brief Summary

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This is a study to examine the effect of combining chronic oral azithromycin with inhaled tobramycin in adolescent and adult subjects with cystic fibrosis who are chronically infected with P. aeruginosa.

Detailed Description

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This study is a prospective, randomized, double-blinded, placebo-controlled trial of azithromycin 500mg taken orally thrice weekly vs. placebo in subjects with cystic fibrosis and chronic airway infection with P. aeruginosa who are utilizing chronic inhaled tobramycin therapy. It will include approximately 120 subjects able to complete a primary 6-week study phase. Subjects will be at least 12 years old with a baseline forced expiratory volume at one second (FEV1) between 25-100% predicted. Subjects will continue to use clinically prescribed inhaled tobramycin cycled on/off every 4 weeks. They will be provided over-encapsulated azithromycin 500mg tablets or placebo during the primary study phase. An optional extension phase will be offered to all subjects completing the primary 6-week study. This 8-week extension phase will include an initial 4 weeks without use of inhaled tobramycin or other inhaled antibiotics, followed by a 4-week period with inhaled tobramycin use. All subjects participating in the extension phase of the study will be provided azithromycin 500mg tablets to be taken thrice weekly for the entire 8-week period.

This study will investigate how use of chronic oral azithromycin affects some of the previously demonstrated benefits to health when using inhaled tobramycin. The primary measurements will focus on lung function. Additional measurements will focus on disease-related quality of life as reported by subjects in the trial. Exploratory outcomes, including measurements of safety, are also planned.

Conditions

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Cystic Fibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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azithromycin

azithromycin 500mg tablet over-encapsulated to match placebo in appearance, taken by mouth thrice weekly for 6 weeks

Group Type ACTIVE_COMPARATOR

azithromycin

Intervention Type DRUG

500mg tablet over-encapsulated to match placebo

inhaled tobramycin

Intervention Type DRUG

clinically prescribed inhaled tobramycin used by subjects participating in the study

placebo

encapsulated placebo taken by mouth thrice weekly for 6 weeks

Group Type PLACEBO_COMPARATOR

placebo (for azithromycin)

Intervention Type DRUG

inhaled tobramycin

Intervention Type DRUG

clinically prescribed inhaled tobramycin used by subjects participating in the study

Interventions

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azithromycin

500mg tablet over-encapsulated to match placebo

Intervention Type DRUG

placebo (for azithromycin)

Intervention Type DRUG

inhaled tobramycin

clinically prescribed inhaled tobramycin used by subjects participating in the study

Intervention Type DRUG

Other Intervention Names

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Zithromax

Eligibility Criteria

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Inclusion Criteria

* 12 years old or older
* documented diagnosis of cystic fibrosis
* written informed consent (and assent when applicable)
* at least two respiratory cultures growing P. aeruginosa within the last 12 months
* FEV1% predicted between 25-100%
* use of at least two cycles of inhaled tobramycin within the last 24 weeks
* Off TISP and other inhaled anti-pseudomonal antibiotics for at least 2 weeks at Visit 1 and remain off of any inhaled antibiotics for an additional 2 weeks before starting inhaled tobramycin
* most recent liver function test results less than 4 times the upper limit of normal, obtained within the last 12 months
* prior or current use of azithromycin for at least four consecutive weeks
* stable clinical status and therapeutic regimen

Exclusion Criteria

* weight \<40 kg
* positive pregnancy test, lactating, or unwillingness to practice a pre-defined form of contraception, which includes abstinence
* inability to perform reproducible spirometry
* inability or unwillingness to cycle off of inhaled tobramycin for one 4-week period and without use of any additional inhaled antibiotics
* respiratory culture with Burkholderia cepacia complex species within 24 months or with nontuberculous mycobacteria within 18 months of screening
* use of intravenous or oral anti-pseudomonal antibiotics within 4 weeks of screening
* use of investigational therapy within 4 weeks of screening
* use of systemic corticosteroids equivalent to a daily dose more than 10mg of prednisone
* use of nelfinavir, warfarin, haloperidol, or methadone (concern of drug interaction with azithromycin)
* initiation of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy within 30 days
* ECG abnormality at screening requiring prompt further medical attention, or QTc interval \>480 msec for males and \>486 msec for females
* any other condition that, in the opinion of the site investigator, would compromise the safety of the subject or quality of the data
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Cystic Fibrosis Foundation

OTHER

Sponsor Role collaborator

CF Therapeutics Development Network Coordinating Center

NETWORK

Sponsor Role collaborator

Seattle Children's Hospital

OTHER

Sponsor Role lead

Responsible Party

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David Nichols, MD

Associate Professor of Pediatrics

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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David P Nichols, MD

Role: PRINCIPAL_INVESTIGATOR

National Jewish Health

Locations

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Children's Hospital of Los Angeles

Los Angeles, California, United States

Site Status

Stanford University Medical Center

Palo Alto, California, United States

Site Status

Rady Children's Hospital and Health Center at the University of California San Diego

San Diego, California, United States

Site Status

National Jewish Health

Denver, Colorado, United States

Site Status

Yale University School of Medicine

New Haven, Connecticut, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

The Nemours Children's Clinic - Orlando

Orlando, Florida, United States

Site Status

Nemours Children's Clinic - Pensacola

Pensacola, Florida, United States

Site Status

Saint Luke's Cystic Fibrosis Center of Idaho

Boise, Idaho, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Saint Francis Medical Center

Peoria, Illinois, United States

Site Status

Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

Maine Medical Partners Pediatric Specialty Care

Portland, Maine, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

University of Massachusetts Memorial Health Care

Worcester, Massachusetts, United States

Site Status

University of Michigan Health System

Ann Arbor, Michigan, United States

Site Status

Helen DeVos Children's Hospital

Grand Rapids, Michigan, United States

Site Status

The Minnesota Cystic Fibrosis Center

Minneapolis, Minnesota, United States

Site Status

Children's Mercy Kansas City

Kansas City, Missouri, United States

Site Status

Cardinal Glennon Children's Medical Center

St Louis, Missouri, United States

Site Status

St. Louis Children's Hospital

St Louis, Missouri, United States

Site Status

Monmouth Medical Center

Long Branch, New Jersey, United States

Site Status

Beth Israel Medical Center

New York, New York, United States

Site Status

Children's Hospital of New York

New York, New York, United States

Site Status

University of Rochester Medical Center Strong Memorial

Rochester, New York, United States

Site Status

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

University Hospitals Case Medical Center/Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

Site Status

Dayton Children's Hospital

Dayton, Ohio, United States

Site Status

Oregon Health Sciences University

Portland, Oregon, United States

Site Status

Hershey Medical Center Pennsylvania State University

Hershey, Pennsylvania, United States

Site Status

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Cook Children's Medical Center

Fort Worth, Texas, United States

Site Status

Intermountain Cystic Fibrosis Center

Salt Lake City, Utah, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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1R01HL124053-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NICHOL15A0

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

TEACH-IP-15

Identifier Type: -

Identifier Source: org_study_id

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