A double-blind, randomised, placebo-controlled phase III study of the efficacy of a bivalent Pseudomonas aeruginosa flagella vaccine in patients with cystic fibrosis
| ISRCTN | ISRCTN98785888 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN98785888 |
| Secondary identifying numbers | PEI 0169/02 |
- Submission date
- 17/10/2006
- Registration date
- 12/12/2006
- Last edited
- 08/09/2008
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Not provided at time of registration
Contact information
Prof Gerd Doering
Scientific
Scientific
Wilhelmstrasse 31
Tuebingen
72074
Germany
Study information
| 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 |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Scientific title | |
| Study acronym | FLA Vaccine TRIAL |
| Study objectives | 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(s) | 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. |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | 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 study start date | 06/05/1997 |
| Completion date | 19/04/2003 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 2 Years |
| Upper age limit | 18 Years |
| Sex | Not Specified |
| Target number of participants | 483 |
| Key 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% |
| Key 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 |
| Date of first enrolment | 06/05/1997 |
| Date of final enrolment | 19/04/2003 |
Locations
Countries of recruitment
- Austria
- France
- Germany
- Italy
Study participating centre
Wilhelmstrasse 31
Tuebingen
72074
Germany
72074
Germany
Sponsor information
The Society for the fight of Cystic Fibrosis (The Gesellschaft zur Bekämpfung der Mukoviszidose e.V.) (Germany)
Research organisation
Research organisation
In den Dauen 6
Bonn
53117
Germany
"ROR" |
https://ror.org/028ew8k17 |
|---|
Funders
Funder type
Research organisation
The study was supported by grants from:
No information available
The Society for the fight of Cystic Fibrosis (The Gesellschaft zur Bekämpfung der Mukoviszidose e.V.) (Germany)
No information available
Cystic Fibrosis Association (Vaincre la Mucoviscidose) (France)
No information available
The Association for Cystic Fibrosis of Lombardia (LAssoziazione de la Fibrosi Cistica Lombardia) (Italy)
No information available
Hospital Meyer (Ospedale Meyer) (Italy)
No information available
Association for Cystic Fibrosis (Verband der Cystischen Fibrose) (Austria)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
