Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
PEI 0169/02
Study information
Scientific title
Acronym
FLA Vaccine TRIAL
Study hypothesis
Administration of a bivalent P. aeruginosa flagella vaccine to patients with cystic fibrosis (CF) would significantly lower the frequency of P. aeruginosa pulmonary infection by 66%.
Ethics approval
Informed consent was obtained from all patients or their parents, and the study protocol was approved by the institutional review boards at the participating hospitals, the biostatistician, the International Steering Committee, the Supervisory Board and the respective administrative bodies of the European countries Germany, Italy, France and Austria.
The study was conducted according to International Conference on Harmonisation (ICH)/Good Clinical Pratice (GCP) and CONSORT guidelines.
Study design
The phase III study was a randomised, double-blind, placebo-controlled, multi-centre trial.
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Cystic fibrosis
Intervention
For each patient a package of four pre-filled 1 ml syringes, numbered with the randomisation code, and containing either 40 µg flagella protein (20 µg flagella of subtype a0a1a2 from P. aeruginosa strain 1210 and 20 µg flagella of subtype b from P. aeruginosa strain 5142), 2 mg aluminium hydroxide and 0.1 mg thiomersal, or 2 mg aluminium hydroxide and 0.1 mg thiomersal only, was provided.
The 483 patients were randomised in blocks of 12 patients in a 1:1 ratio between vaccine and placebo using random numbers, generated by the algorithm of Wichmann and Hill, stratified by centre. The patients received the contents of three syringes by intramuscular injection during CF clinic visits, one syringe every four weeks and alternating between the right and left upper arm. After one year the content of a fourth syringe was injected in the left upper arm.
Intervention type
Drug
Phase
Phase III
Drug names
Pseudomonas aeruginosa flagella vaccine
Primary outcome measure
The lower frequency or complete absence of P. aeruginosa pulmonary infection in the vaccine group compared to the placebo group during the two-year observation period of the study. Infection was defined by having one or more P. aeruginosa positive throat swabs or positive serum antibody titres against the P. aeruginosa antigens alkaline proteinase, elastase and exotoxin A (primary endpoint one). The primary endpoint two was defined as three positive throat swabs and/or three positive serum antibody titres against the P. aeruginosa antigens alkaline proteinase, elastase and exotoxin A within a 12 month period during the study, to assess chronic P. aeruginosa infection in the patient groups.
Secondary outcome measures
Secondary criteria for efficacy were:
1. A difference between the vaccine and the placebo groups in specific serum antibody titres against the inoculated antigens;
2. The distribution of P. aeruginosa flagella subtype strains between the vaccine and the placebo groups.
Overall trial start date
06/05/1997
Overall trial end date
19/04/2003
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Cystic fibrosis that has been diagnosed according to conventional criteria
2. Patients aged between two and 18 years
3. No infection with P. aeruginosa as assessed by a negative throat swab culture and negative serum antibody titres against the P. aeruginosa antigens exotoxin A
4. Alkaline protease and elastase in enzyme-linked immunosorbent assays (ELISAs)
5. A forced expiratory volume in one second (FEV1) of at least 70% of the predicted value
6. A weight-to-height ratio of at least 90%
7. An oxygen saturation of at least 92%
Participant type
Patient
Age group
Child
Gender
Not Specified
Target number of participants
483
Participant exclusion criteria
1. A known allergy to thiomersal or mercury
2. A prolonged bleeding time or a pathological partial thromboplastin time (PTT) value
3. Were using immunosuppressive drugs such as systemic corticosteroids
4. Participating in other clinical studies
Recruitment start date
06/05/1997
Recruitment end date
19/04/2003
Locations
Countries of recruitment
Austria, France, Germany, Italy
Trial participating centre
Wilhelmstrasse 31
Tuebingen
72074
Germany
Funders
Funder type
Research organisation
Funder name
The study was supported by grants from:
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
The Society for the fight of Cystic Fibrosis (The Gesellschaft zur Bekämpfung der Mukoviszidose e.V.) (Germany)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Cystic Fibrosis Association (Vaincre la Mucoviscidose) (France)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
The Association for Cystic Fibrosis of Lombardia (LAssoziazione de la Fibrosi Cistica Lombardia) (Italy)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Hospital Meyer (Ospedale Meyer) (Italy)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Association for Cystic Fibrosis (Verband der Cystischen Fibrose) (Austria)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list