Condition category
Nutritional, Metabolic, Endocrine
Date applied
17/10/2006
Date assigned
12/12/2006
Last edited
08/09/2008
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Gerd Doering

ORCID ID

Contact details

Wilhelmstrasse 31
Tuebingen
72074
Germany

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 measures

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

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

Sponsor information

Organisation

The Society for the fight of Cystic Fibrosis (The Gesellschaft zur Bekämpfung der Mukoviszidose e.V.) (Germany)

Sponsor details

In den Dauen 6
Bonn
53117
Germany

Sponsor type

Research organisation

Website

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 (L’Assoziazione 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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes