Study of Aztreonam for Inhalation in Children With Cystic Fibrosis and New Infection of the Airways by Pseudomonas Aeruginosa Bacteria

NCT ID: NCT03219164

Last Updated: 2022-06-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 149 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-28
• Study Completion Date: 2021-09-23

Brief Summary

The primary objective of this study is to evaluate the safety and efficacy of a 14-day course versus a 28-day course of aztreonam for inhalation solution (AZLI) in pediatric participants with new onset Pseudomonas aeruginosa respiratory tract infection or colonization.

Conditions

Pseudomonas Aeruginosa Respiratory Tract Infection/Colonization; Cystic Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

AZLI + Placebo

75 mg/ml of aztreonam will be administered thrice daily (TID) for 14 days followed by placebo to match (PTM) aztreonam TID for 14 days.

Group Type: EXPERIMENTAL

AZLI

Intervention Type: DRUG

Administered via the PARI Altera® Nebulizer System. Participants \< 2 years will receive via the SmartMask® Baby, 2 to \< 6 years via the SmartMask Kids® and \> 6 years via the nebulizer mouthpiece.

Placebo

Intervention Type: DRUG

Administered via the PARI Altera® Nebulizer System. Participants \< 2 years will receive via the SmartMask® Baby, 2 to \< 6 years via the SmartMask Kids® and \> 6 years via the nebulizer mouthpiece.

AZLI

75 mg/ml of aztreonam will be administered TID for 28 days.

Group Type: EXPERIMENTAL

AZLI

Intervention Type: DRUG

Administered via the PARI Altera® Nebulizer System. Participants \< 2 years will receive via the SmartMask® Baby, 2 to \< 6 years via the SmartMask Kids® and \> 6 years via the nebulizer mouthpiece.

Interventions

AZLI

Administered via the PARI Altera® Nebulizer System. Participants \< 2 years will receive via the SmartMask® Baby, 2 to \< 6 years via the SmartMask Kids® and \> 6 years via the nebulizer mouthpiece.

Intervention Type: DRUG

Placebo

Administered via the PARI Altera® Nebulizer System. Participants \< 2 years will receive via the SmartMask® Baby, 2 to \< 6 years via the SmartMask Kids® and \> 6 years via the nebulizer mouthpiece.

Intervention Type: DRUG

Other Intervention Names

Cayston®; Aztreonam

Eligibility Criteria

Inclusion Criteria

• Diagnosis of cystic fibrosis (CF) as determined by the 2008 CF Consensus Conference criteria: Sweat chloride level ≥ 60 milliequivalents per liter (mEq/L) by quantitative pilocarpine iontophoresis; or a genotype with 2 identifiable mutations consistent with CF; or an abnormal nasal transepithelial potential difference (NPD), and 1 or more clinical features consistent with CF
• Documented new onset of positive respiratory tract culture for PA within 30 days of screening defined as either first lifetime documented PA-positive culture, or PA recovered after at least a 2-year history of PA-negative respiratory cultures (at least 2 cultures per year)
• Forced expiratory volume in one second (FEV1) ≥ 80% predicted (for subjects ≥ 6 years of age who can reliably perform spirometry assessments)
• Clinically stable with no evidence of acute significant respiratory symptoms that would require administration of intravenous (IV) antipseudomonal antibiotics, oxygen supplementation, or hospitalization

Exclusion Criteria

• Use of IV or inhaled antipseudomonal antibiotics within 2 years of screening
• Use of oral antipseudomonal antibiotics for a respiratory event within 30 days of study entry (screening visit)
• History of intolerance to inhaled short acting β2 agonists
• History of lung transplantation
• Current requirement for daily continuous oxygen supplementation or requirement of more than 2 L/minute at night
• Hospitalization for a respiratory event within 30 days prior to screening
• Changes in bronchodilator, corticosteroid, dornase alfa, or hypertonic saline medications within 7 days prior to screening.
• Significant changes (per investigators discretion) in physiotherapy technique or schedule within 7 days prior to screening
• Abnormal renal or hepatic function results at most recent test within the previous 12 months, defined as Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times upper limit of normal (ULN), or Serum creatinine > 2 times ULN for age
• Presence of a condition or abnormality that would compromise the subject's safety or the quality of the study data, in the opinion of the Investigator
• Known hypersensitivity to aztreonam, its metabolites, or formulation excipients in AZLI
• Respiratory cultures performed within 24 months prior to screening that are positive for ANY Burkholderia spp. or Non-tuberculous mycobacteria (NTM)

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

University of California San Francisco (UCSF) - Benioff Children's Hospital

San Francisco, California, United States

Children's National Health System

Washington D.C., District of Columbia, United States

Johns Hopkins All Children's Hospital Outpatient Care Center

St. Petersburg, Florida, United States

Ann & Robert H Lurie Childrens Hospital of Chicago

Chicago, Illinois, United States

Corner Children's Hospital

Chicago, Illinois, United States

University of Mississippi Medical center

Jackson, Mississippi, United States

Clinical Research of Charlotte

Charlotte, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

USC Department of Pediatrics/Division of Pediatric Pulmonology

Columbia, South Carolina, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

The University of Texas Health Science Center at Tyler

Tyler, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Medizinische Universitat Graz

Graz, , Austria

Medizinische Universitat Innsbruck

Innsbruck, , Austria

Hopital Universitaire des Enfants Reine Fabiola

Brussels, , Belgium

UZ Antwerpen

Edegem, , Belgium

Aarhus University Hospital

Aarhus N, , Denmark

Rigshospitalet

Copenhagen, , Denmark

Hopital des enfants - GH Pellegrin

Bordeaux, , France

CHU Grenoble Alpes

Grenoble, , France

Hopital Robert Debre APHP

Paris, , France

Universitatsklinikum Essen

Essen, , Germany

Stadtisches Krankenhaus Kiel

Kiel, , Germany

General Hospital of Thessaloniki,3rd Dept of Pediatrics

Thessaloniki, , Greece

Rambam Health Corporation

Haifa, , Israel

Lady Davis Carmel Medical Center

Haifa, , Israel

Hadassah University Hospital Mount Scopus

Jerusalem, , Israel

Schneider Children's Medical Center of Israel

Petah Tikva, , Israel

Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele

Catania, , Italy

Fondazione IRCCS ca Granda

Milan, , Italy

Azienda Ospedaliera Universitaria "Federico II"

Napoli, , Italy

Azienda Policlinico Umberto - Universita La Sapienza di Roma

Roma, , Italy

Ospedale Pediatrico Bambino Gesu

Roma, , Italy

Azienda Ospedaliera Universitaria Integrata Verona

Verona, , Italy

VU University Medical Center

Amsterdam, , Netherlands

Hospital Universitario Vall d Hebron

Barcelona, , Spain

Hospital Sant Joan de Deu

Esplugues de Llobregat, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Regional Universitario de Malaga

Málaga, , Spain

Corporacio Sanitaria Parc Tauli

Sabadell, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Hospital Clinico Universitario

Valencia, , Spain

NHS Grampian

Aberdeen, , United Kingdom

Birmingham Children's Hospital NHS Foundation Trust

Birmingham, , United Kingdom

Royal Devon and Exeter Foundation NHS Trust

Exeter, , United Kingdom

University Hospitals of Leicester NHS trust

Leicester, , United Kingdom

Barts and the London Children's Hospital

London, , United Kingdom

Kings College Hospital NHS foundation Trust

London, , United Kingdom

Royal Manchester Children's Hospital

Manchester, , United Kingdom

South Tees Hospitals NHS Foundation Trust

Middlesbrough, , United Kingdom

Sheffield Children's Hospital NHS Trust

Sheffield, , United Kingdom

Southampton University Hospitals NHS trust, Southampton General Hospital

Southampton, , United Kingdom

University Hospitals of North Midlands NHS trust Royal Stoke University Hospital

Stoke-on-Trent, , United Kingdom

Countries

United States; Austria; Belgium; Denmark; France; Germany; Greece; Israel; Italy; Netherlands; Spain; United Kingdom

References

Gilchrist FJ, Bui S, Gartner S, McColley SA, Tiddens H, Ruiz G, Stehling F, Alani M, Gurtovaya O, Bresnik M, Watkins TR, Frankovic B, Skov M; ALPINE2 study investigators. ALPINE2: Efficacy and safety of 14-day vs 28-day inhaled aztreonam for Pa eradication in children with cystic fibrosis. J Cyst Fibros. 2024 Jan;23(1):80-86. doi: 10.1016/j.jcf.2023.06.008. Epub 2023 Jul 15.

Reference Type: DERIVED

PMID: 37455237 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-002749-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-205-1850

Identifier Type: -

Identifier Source: org_study_id