Pseudomonas Aeruginosa - Inhalation treatment, biomarkers and quality of life

• Register: EUCTR
• Last refreshed on: 2 October 2017
• Main ID: EUCTR2015-003662-87-DK
• Date of registration: 22/09/2015
• Prospective Registration: Yes
• Primary sponsor: Aarhus University Hospital, Department of Respiratory Medicine
• Public title: Pseudomonas Aeruginosa - Inhalation treatment, biomarkers and quality of life
• Scientific title: Pseudomonas Aeruginosa - Inhalation treatment, biomarkers and quality of life - Pseudomonas, Tazocin or Colistin
• Date of first enrolment: 13/11/2015
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-003662-87
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Denmark

Contacts

• Name: Department of Respiratory Medicine
• Affiliation: Aarhus University Hospital

• Name: Department of Respiratory Medicine
• Affiliation: Aarhus University Hospital

Key inclusion & exclusion criteria

Inclusion criteria:
In order to be eligible to participate in this study, the patient must meet all of the following criteria:
· Signed informed consent to participate in the study in accordance with local
regulations
· Diagnosed with a chronic pulmonary disease by lung functions test or CT
· Diagnosed with one positive sputum sample with PA during the last year
· Age 18 - 85 years inclusive
· Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study
procedures specified in the protocol.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70

Exclusion criteria:
A potential subject who meets any of the following criteria will be excluded from participation in this study:
· Prophylactic treatment with any other antibiotic
· Allergy to tazocin, ciprofloxacin or colistimethate-sodium
· Patients who are pregnant or planning a pregnancy
· Patients with any solid organ transplant
· Patients with cystic fibrosis
· Patients on assisted ventilation
· Bronchiectasis as a consequence of cystic fibrosis or focal endobronchial
lesion or otherwise curable causes (e.g. foreign body aspiration)
· Be considered "terminally ill" or listed for transplantation
· Actively treated Mycobacterium tuberculosis or other mycobacteria
· Patients in a condition or in a situation, which in the investigator's opinion
may put the subject at significant risk, may confound results or may interfere
significantly with the patient's participation in the study



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic pulmonary disease patients, except cystic fibrosis patients, with confirmed pulmonary infection by sputum sample positive for Pseudomonas Aeruginosa.
MedDRA version: 18.1 Level: LLT Classification code 10051190 Term: Pneumonia Pseudomonas aeruginosa System Organ Class: 100000004862
MedDRA version: 18.1 Level: LLT Classification code 10050700 Term: Chronic respiratory disease NOS System Organ Class: 100000004855

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Trade Name: colistimethate sodium (promixin)
Pharmaceutical Form: Inhalation vapour, powder
INN or Proposed INN: COLISTIMETHATE SODIUM
CAS Number: 8068-28-8
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 1000000-

Trade Name: Piperacillin with Tazobactam (tazocin)
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: PIPERACILLIN
Other descriptive name: PIPERACILLIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4000-
INN or Proposed INN: TAZOBACTAM
Other descriptive name: TAZOBACTAM
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Primary end point(s): 1: Number of positive Pseudomonas (PA) sputum cultures after treatment and 12, 26 and 52 weeks after end of treatment. If possible PCR for PA oprf gene.

2: Number of specific immune deficiencies and their relation to baseline clinical status and clinical outcome.

3: Number of precipitating antibodies during intervention and follow-up, measured 26 and 52 weeks after treatment.

Main Objective: Chronic pulmonary disease patients often gets bacterial pneumonia with the bacteria Pseudomonas Aeruginosa, often with severe morbidity and mortality as a result. It is well examined for patients with cystic fibrosis, but for non-cystic fibrosis chronic pulmonary disease patients our knowledge is sparse. The standard treatment at the moment is 14 days of a combination of intravenously and oral antibiotic. We will examine whether we can more effectively clear the infection with inhaled colistimethate and oral ciprofloxacin. Furthermore we will follow the patient with pulmonary function tests, sputum samples for relapse infections and clinical assessments.

Secondary Objective: Secondary end points is to examine the current and future immune status of the infected patient and to examine their experience of “quality of life” between the control and intervention group during 1 year of follow up. Further more we will examine whether we can make an assessment of the risk for the patient when they debut with their infection by means of biomarkers.

Timepoint(s) of evaluation of this end point: Each patient will be followed for a year. The trial will run for 2-3 years.

Secondary Outcome(s)

Secondary end point(s): 1: Relative change from baseline of FVC (% predicted), FEV1 (% predicted), DLCO and 6minuttes walking test (6MWT) at follow-up.
2: Subjective change in dyspnea, cough and quality of life after treatment and at follow-up.
3: Numbers of exacerbations and hospital admissions after treatment
4: Assess whether immune deficiencies can be used as a prognostic factor
5: Changes in immunoglobulins, interferon gamma and lymphocytes during follow-up
6: Number of pre-treatment precipitating antibodies and their relation to the number of cleared PA infections, change in lung function and dyspnea score at 12, 26 and 52 weeks after treatment.
7: Correlation between detected exotoxins, exoenzymes and TNFR75 on clinical outcome determined by the numbers of exacerbations, number of sputum eradications of PA, time to sputum eradication of PA, time to stabilization of pulmonary function, 6MWT and survival.
8: Correlation between detected plasma elastase and alkaline protease on clinical outcome determined by the numbers of exacerbations, number of sputum eradications of PA, time to sputum eradication of PA, time to stabilization of pulmonary function, 6MWT and survival.

Timepoint(s) of evaluation of this end point: Each patient will be followed for a year. The trial will run for 2-3 years.

Secondary ID(s)

Pseud-0708-MLJ

Source(s) of Monetary Support

Danish Lung Association