Aztreonam Lysine for Pseudomonas Infection Eradication Study
- Conditions
- Cystic Fibrosis
- Interventions
- Registration Number
- NCT01375049
- Lead Sponsor
- Gilead Sciences
- Brief Summary
This is an open-label, multi-center study in pediatric patients age 3 months to less than 18 years with cystic fibrosis (CF) and newly detected Pseudomonas aeruginosa (PA) pulmonary colonization/infection. All eligible participants will be treated with a 28-day course of Aztreonam for Inhalation Solution (AZLI) 75 mg 3 times daily. After completion of study drug, subjects will be followed up through Day 196 for safety and recurrence of PA.
The primary objective is to evaluate the proportion of participants with PA-negative cultures at all time points during a 6-month monitoring period (through Day 196) after cessation of AZLI treatment. Microbiological cultures will be obtained at Baseline, Day 28 (end of AZLI treatment), Day 56 (1 month after completing AZLI treatment), Day 112 (3 months after completing AZLI treatment), and Day 196 (6 months after completing AZLI treatment).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 105
- Males or females age 3 months to less than 18 years
- Diagnosis of CF as determined by the 1997 CF Consensus Conference criteria:
- Documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test OR
- Abnormal nasal transepithelial potential difference test OR
- Two well-characterized, disease-causing genetic mutations in the CF transmembrane conductance regulator (CFTR) gene AND
- One or more clinical features consistent with CF
- Documented new onset of positive lower respiratory tract culture (e.g., throat swab, sputum, or BAL) for PA within 30 days of study entry (prior to screening visit) 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 1 second (FEV1) ≥ 80% predicted at screening visit (subjects ≥ 6 years of age)
- Clinically stable with no evidence of significant respiratory symptoms or, if obtained for clinical evaluation, no chest radiograph findings at screening that would have required administration of IV antipseudomonal antibiotics, oxygen supplementation, or hospitalization.
- All sexually active females who were of childbearing potential must agree to use a highly effective method of contraception during heterosexual intercourse throughout the study. Females utilizing hormonal contraceptives as a birth control method must have used the same method for at least 3 months prior to study drug dosing.
- Males must agree to use barrier contraception (condom with spermicide) during heterosexual intercourse from screening through to study completion and for 90 days from the last dose of study investigational medicinal product
- Participants and/or parent/guardian must be able to give written informed consent prior to any study related procedure
- Use of IV or inhaled antipseudomonal antibiotics within 2 years of study entry (screening visit)
- Use of oral antipseudomonal antibiotics within 30 days of study entry (screening visit)
- History of sputum or throat swab culture yielding Burkholderia spp. within 2 years prior to screening visit
- History of local or systemic hypersensitivity to monobactam antibiotics
- History of intolerance to inhaled short acting beta 2 agonists
- History of lung transplantation
- History of AZLI (or Cayston®) administration
- Administration of any investigational drug or device within 28 days prior to screening visit or within 6 half-lives of the investigational drug (whichever is longer)
- Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone per day or 20 mg prednisone every other day
- Current requirement for daily continuous oxygen supplementation or requirement of more than 2 L/minute at night
- Hospitalization for pulmonary-related illness within 28 days prior to screening visit
- Changes in or initiation of chronic azithromycin treatment within 28 days prior to screening visit
- Changes in antimicrobial, bronchodilator (BD), corticosteroid, dornase alfa, or hypertonic saline medications within 7 days prior to screening visit; for participants on a stable regimen of hypertonic saline (28 days on/28 days off), beginning or ending a cycle of hypertonic saline is allowed
- Changes in physiotherapy technique or schedule within 7 days prior to screening visit
- 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
- Pregnant or lactating females; a negative urine pregnancy test is required for all females of childbearing potential (unless surgically sterile), and confirmatory serum pregnancy test in the event of an initial positive urine test result
- Any serious or active medical or psychiatric illness (including drug or alcohol abuse), which in the opinion of the investigator, would interfere with treatment, assessment, or compliance with the protocol
- Presence of a condition or abnormality that would compromise the patient's safety or the quality of study data, in the opinion of the investigator
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Aztreonam for Inhalation Solution (AZLI) Aztreonam for Inhalation Solution (AZLI) Participants will receive one 28-day course of AZLI, then will be followed for a 24-week period (through Day 196).
- Primary Outcome Measures
Name Time Method Percentage of Participants With PA-negative Cultures at All Time Points After Cessation of Active Treatment (Evaluable Analysis Set) Day 28 to Day 196 The percentage of participants with PA-negative cultures at all time points after cessation of active treatment at Day 28 (assessed at Days 56, 112, and 196) was summarized for the Evaluable Analysis Set.
Percentage of Participants With PA-negative Cultures at All Time Points After Cessation of Active Treatment (Sensitivity Analysis Set) Day 28 to Day 196 The percentage of participants with PA-negative cultures at all time points after cessation of active treatment at Day 28 (assessed at Days 56, 112, and 196) was summarized for the Sensitivity Analysis Set.
- Secondary Outcome Measures
Name Time Method Change From Baseline in FEV1% Predicted Baseline to Days 28, 56, 112, and 196 Spirometry assessments were performed only in participants ≥ 6 years of age. Forced expiratory volume in 1 second (FEV1) % predicted was defined as FEV1 of the participant divided by the average FEV1 in the population for any person of similar age, sex and body composition.
Use of Additional (Non-study) Antipseudomonal Antibiotics Baseline to Day 196 The percentage of participants who used additional (non-study) antipseudomonal antibiotics (an indication of PA exacerbation) while on treatment and posttreatment was summarized.
Change From Baseline in CFQ-R RSS Score Baseline to Days 28, 56, 112, and 196 Respiratory symptoms (eg, coughing, congestion, wheezing) were assessed with the Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS) only in participants ≥ 6 years of age. The range of scores (units) is 0 to 100 with higher scores indicating fewer symptoms.
Percentage of Participants With PA-negative Cultures Days 28, 56, 112, and 196 The percentage of participants with a PA-negative culture was summarized at each visit.
Change From Baseline in Weight Baseline to Days 28, 56, 112, and 196 Change From Baseline in Height Baseline to Days 28, 56, 112, and 196 Change From Baseline in Body Mass Index (BMI) Baseline to Days 28, 56, 112, and 196 Pharmacokinetics (PK) Peak and Trough Plasma Concentrations of Aztreonam Day 1 (1 hour postdose) and Day 28 (immediately prior to dosing) The plasma concentration of aztreonam for participants \< 6 years of age was obtained 1 hour after the first dose of AZLI on Day 1 and immediately prior to the last dose of AZLI on Day 28.
Trial Locations
- Locations (58)
Nemours Children's Clinic- Jacksonville
🇺🇸Jacksonville, Florida, United States
Nemours Childrens Clinic Orlando
🇺🇸Orlando, Florida, United States
Children's Memorial Hospital
🇺🇸Chicago, Illinois, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Children's Mercy Hospital and Clinics
🇺🇸Kansas City, Missouri, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Saint Louis University
🇺🇸St. Louis, Missouri, United States
Akron Children's Hospital
🇺🇸Akron, Ohio, United States
Cohen Children's Medical Center of NY
🇺🇸Great Neck, New York, United States
UNC Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Toledo Children's Hospital CF Research Center
🇺🇸Toledo, Ohio, United States
PennState Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Pediatric Respiratory Department, Ghent University Hospital
🇧🇪Ghent, Belgium
CHU de Boredaux Hôpital des Enfants - Pellegrin CEDRE
🇫🇷Bordeaux, France
CRCM mixte / CHU ESTAING
🇫🇷Clermont Ferrand, France
CHI de Créteil Departement pediatrie
🇫🇷Creteil, France
Centre hospitalier Robert Bissons CRCM - service pédiatrie
🇫🇷Lisieux, France
Hopital Robert Debre
🇫🇷Paris, France
Centre de Ressources et de Compétences sur la Mucoviscidose ( CRCM), Roscoff, France
🇫🇷Roscoff, France
Charité Campus Virchow Klinikum, Universitätsmedizin Berlin, Klinik für Pädiatrie mit Schwerpunkt Pneumologie/Immunolgie Prof. Wahn
🇩🇪Berlin, Germany
Klinik fur Kinder- und Jugendmedizinim St Josef-Hopsital
🇩🇪Bochum, Germany
Universitätsklinikum Essen, Zentrum für Kinderheilkunde - Abteilung Allg. Kinderheilkunde/Neuropaediatrie
🇩🇪Erlangen, Germany
Universitaetsklinikum Bonn-Zentrum fuer Kinderheikunde
🇩🇪Essen, Germany
Christiane Herzog CF-Center, Goethe University Hospital
🇩🇪Frankfurt, Germany
Universitätsklinikum Gießen und Marburg GmbH
🇩🇪Giessen, Germany
Azienda Ospedaliero-Universitaria di Catania, Dipartimento di Pediatria, UO Broncopneumologia Pediatrica
🇮🇹Catania, Italy
Fondazione IRCCS, Ospedale Pediatrico, Bambino Gesu' di Roma
🇮🇹Rome, Italy
Division of Respiratory Medicine and Allergology, Department of Pediatrics, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
🇳🇱Rotterdam, Netherlands
ISPL Centrum Medyczne
🇵🇱Bialystok, Poland
Specjalistyczny Zespół Opieki Zdrowotnej nad Matką i Dzieckiem, Poradnia Leczenia Mukowiscydozy
🇵🇱Gdansk, Poland
Hospital infantil Universitario Niño Jesus, Servicio de Neumología Pediatrica
🇪🇸Madrid, Spain
Hospital Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Vall D' Hebron Pediatric Pneunmonology and Cystic Fibrosis Clinic
🇪🇸Barcelona, Spain
Hospital Infantil La Paz
🇪🇸Madrid, Spain
Hospital Materno-Infantil Carlos Haya, Servicio de Neumología Pediatrica
🇪🇸Malaga, Spain
Medizinische Universität Innsbruck Abt. für Kinder- und Jugendheilkunde, Pädiatrie III (Zystische Fibrose)
🇦🇹Innsbruck, Austria
Hôpital Universitaire des Enfants Reine Fabiola Brussels
🇧🇪Brussels, Belgium
Paediatrics, University Hospital Brussels (UZB)
🇧🇪Brussels, Belgium
Pediatric Pulmonology, Dept Pediatrics University Hospital Gasthuisberg
🇧🇪Leuven, Belgium
Longziekten Universitair Medisch (PEDIATRIC), Ultrecht
🇳🇱Utrecht, Netherlands
Instytut Gruźlicy i Chorób Płuc, Klinki Pneumologii i Mukowiscydozy
🇵🇱Rabka Zdroj, Poland
Instytut Matki i Dziecka Klinika Pediatrii
🇵🇱Warszawa, Poland
Cincinnati Children's Hospital
🇺🇸Cincinnati, Ohio, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Children's Hospital Boston
🇺🇸Boston, Massachusetts, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Cystic Fibrosis Centre Paediatric Department, A. Meyer Children Hospital Florence
🇮🇹Florence, Italy
Universita' Federico II di Napoli
🇮🇹Napoli, Italy
Centro Fibrosi Cistica di Verona, Azienda Ospedaliera Universitaria Integrata di Verona
🇮🇹Verona, Italy
Service pédiatrie II Hôpital Necker Enfants Malades
🇫🇷Paris, France
University Children's Hospital
🇩🇪Tubingen, Germany
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Vanderbilt Children's Hospital
🇺🇸Nashville, Tennessee, United States
St. Christopher's Hospital for Children
🇺🇸Philadelphia, Pennsylvania, United States