Clinical trial NCT00333385: Continuous Versus Short Infusions of Ceftazidime in Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Cystic Fibrosis
Pseudomonas Aeruginosa
Pulmonary Exacerbation
Keywords: Ceftazidime
Continuous infusion
Antibiotic course
Lead sponsor: Association Nationale pour les Traitements A Domicile, les Innovations et la Recherche
Sponsor class: OTHER
Collaborators: name: Vaincre la Mucoviscidose
name: GlaxoSmithKline
name: Baxter Healthcare Corporation
name: Roche Pharma AG
First posted: 2006-06-05
Enrollment: 120
Sex: ALL
Minimum age (years): 8
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The aim of this trial was to compare the safety and efficacy of courses of tobramycin and ceftazidime, administered intravenously as either thrice daily short infusions or 24 h continuous infusion, in cystic fibrosis patients with acute exacerbation of chronic pulmonary PA infection. In conventional treatment regimens, ceftazidime is administered in the form of thrice daily short infusions, but pharmacodynamic considerations suggest that continuous infusion could be more effective.

Detailed description: Each patient received two successive IV antibiotic courses during a period of pulmonary exacerbation. One of these courses was delivered as thrice daily 30-minute infusions of ceftazidime in 100 ml of 0.9% sodium chloride, and the other was delivered as a continuous infusion of ceftazidime in 230 ml of 0.9% sodium chloride, over 23 hours. The daily dose of ceftazidime was 200 mg/kg, with a maximum dose of 12 g. For ceftazidime continuous infusion, a loading dose of 60 mg/kg (maximum 2 g) was used. All patients also received tobramycin (10 mg/kg), in the form of one 30-minute infusion per day. Portable devices were used: Intermate® SV 200 (Baxter) for the 30-minute short infusions of ceftazidime and tobramycin, Infusor® LV10 (Baxter) for continuous infusion of ceftazidime.

Eligibility criteria: Inclusion Criteria:

* patients with cystic fibrosis older than 8 years
* with chronic Pseudomonas aeruginosa infection of the respiratory tract
* with at least 2 courses of IV antibiotic in the year before enrolment
* at the time of a pulmonary exacerbation

Exclusion Criteria:

* allergy to ceftazidime or tobramycin
* bronchial colonization with Burkholderia cepacia
* renal impairment
* history of lung transplantation

Primary outcomes:
measure: Change in forced expiratory volume in 1s (FEV1) between the beginning and the end of the IV antibiotic course, expressed as a percentage of the predicted normal value
Secondary outcomes:
measure: the interval between 2 successive IV antibiotic courses
measure: quality of life scores
measure: sputum collected at the beginning and the end of each antibiotic course
measure: plasma ceftazidime concentration at steady state (Css) for ceftazidime continuous infusion, and before (C trough), 30 minutes (Cmax) and 4 hours after (C4) the beginning of ceftazidime short infusion
measure: C-reactive protein, leukocytes and hepatic enzymes levels at the beginning and the end of each IV antibiotic course
Other outcomes:
Locations:
city: Grenoble
country: France
facility: CHU Grenoble
city: Lens
country: France
facility: Centre hospitalier Dr Schaffner
city: Lille
country: France
facility: Hopital Albert Calmette
city: Lille
country: France
facility: Hopital Jeanne de Flandre
city: Marseille
country: France
facility: Hopital Sainte Marguerite
city: Paris
country: France
facility: Assistance Publique des hopitaux de paris, Hopital Trousseau
city: Paris
country: France
facility: Assistance Publique des Hopitaux de Paris, Hopital Cochin
city: Paris
country: France
facility: Assistance Publique des Hopitaux de Paris, Hopital Necker
city: Paris
country: France
facility: Assistance Publique des Hopitaux de Paris, Hopital Robert Debré
city: Rennes
country: France
facility: Hopital Sud
city: Roscoff
country: France
facility: Centre Héliomarin
city: Strasbourg
country: France
facility: Hopital Hautepierre
city: Suresnes
country: France
facility: Hopital Foch
city: Toulouse
country: France
facility: Hopital Larrey
city: Vandoeuvre-les-Nancy
country: France
facility: Hopital de Brabois
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Dominique Hubert, MD
role: PRINCIPAL_INVESTIGATOR
References: