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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03460704




Registration number
NCT03460704
Ethics application status
Date submitted
14/02/2018
Date registered
9/03/2018
Date last updated
29/12/2023

Titles & IDs
Public title
Trial in Non-cystic Fibrosis Bronchiectasis Patients With Chronic Lung Infections Treated With Colistimethate Sodium.
Scientific title
Efficacy and Safety of 12 Months of Therapy With Inhaled Colistimethate Sodium in Subjects With Non-cystic Fibrosis Bronchiectasis Chronically Infected With P. Aeruginosa
Secondary ID [1] 0 0
2016-004558-13
Secondary ID [2] 0 0
Z7224L02
Universal Trial Number (UTN)
Trial acronym
PROMIS-II
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non Cystic Fibrosis Bronchiectasis 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - CMS
Other interventions - Placebo

Experimental: CMS (Colistimethate Sodium) - Inhaled colistimethate sodium twice daily. The active pharmaceutical ingredient consisting of pure CMS one million international units (MIU) / 80 mg of CMS / 33 mg colistin base activity (CBA) was provided as a powder for nebuliser solution in 10R Internation Organization for Standardization (ISO) glass vials.

Placebo Comparator: Placebo - Saline solution inhaled twice daily, provided and administered at the same way of the IMP.


Treatment: Drugs: CMS
1 MIU equivalent to 80 mg colistimethate sodium diluted in 1 mL saline solution 0.45%. Investigational Medicinal Product (IMP) glass vials were shrink wrapped in opaque white plastic and provided in boxes of 30 vials (two weeks of b.i.d. dosing).
The 1 MIU/ml CMS/0.45% saline solution was transferred from the glass vial into a specific nebuliser system fitted with a 0.3 mL medication chamber, for administration by inhalation. This delivered a nominal dose of 0.3 MIU/24 mg CMS (11 mg CBA) from the device.
The first dose of the IMP was administered at the site under the supervision of the site staff and subjects were instructed how to prepare and self-administer the IMP at home via a specific nebuliser system, b.i.d. (morning and evening) over aperiod of 12 month.
At least 10 minutes (min) before each administration, an inhaled short-acting bronchodilator (e.g. salbutamol/albuterol), supplied by the Sponsor, could be taken to improve tolerability.

Other interventions: Placebo
1 mL saline solution 0.45%. The placebo was made up of identical empty glass vials to which the same saline solution diluent was added in exactly the same way as the reconstitution of the active treatment by injecting the diluent through the rubber stopper. The glass vials were shrink wrapped with opaque white plastic to mantain the blind.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean Annual Non-cystic Fibrosis Bronchiectasis (NCFB) Pulmonary Exacerbation Rate
Timepoint [1] 0 0
12 months

Eligibility
Key inclusion criteria
1. are able and willing to give informed consent, following a detailed explanation of
partecipation in the protocol and signed consent obtained;

2. aged 18 years or older of either gender;

3. diagnosed with NCFB by computerised tomography (CT) or high-resolution CT(HRCT) as
recorded in the subject's notes and this is their predominant condition being treated;

4. had at least 2 NCFB pulmonary exacerbations requiring oral or inhaled antibiotics or 1
NCFB pulmonary exacerbation requiring intravenous antibiotics in the 12 months
preceding the Screening Visit (Visit 1) and had no pulmonary exacerbation with or
without treatment during the period between Visit 1 and Visit 2;

5. have a documented history of P. aeruginosa infection;

6. are clinically stable and have not required a change in pulmonary treatment for at
least 30 days before the Screening Visit (Visit 1);

7. have pre-bronchodilator FEV1 =25% of predicted;

8. had a positive sputum culture for P. aeruginosa from an adequate sample taken at the
Screening Visit (Visit 1) or during the screening period.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. known bronchiectasis as a consequence of cystic fibrosis (CF);

2. known history of hypogammaglobulinaemia requiring treatment with immunoglobulin,
unless fully replaced and considered immuno-competent by the Investigator;

3. myasthenia gravis or porphyria;

4. severe cardiovascular disease such as severe uncontrolled hypertension, ischaemic
heart disease or cardiac arrhythmia and any other conditions that would confound the
evaluation of safety, in the opinion of the Investigator;

5. had major surgery in the 3 months prior to the Screening Visit (Visit 1) or planned
inpatient major surgery during the study period;

6. receiving treatment for allergic bronchopulmonary aspergillosis (ABPA);

7. massive haemoptysis (greater than or equal to 300 mL or requiring blood transfusion)
in the preceding 4 weeks before Screening Visit (Visit 1) or between Visit 1 and Visit
2;

8. respiratory failure that would compromise patient safety or confound the evaluation of
safety or efficacy of the study in the opinion of the Investigator;

9. current active malignancy, except for basal cell carcinoma or squamous cell carcinoma
of the skin without metastases;

10. taking immunosuppressive medications (such as azathioprine, cyclosporine, tacrolimus,
sirolimus, mycophenolate, rituximab), and/or anti cytokine medications (such as
anti-IL-6 and anti-tumour alpha necrosis factor products) in the preceding year before
the Screening Visit (Visit 1);

11. known history of human immunodeficiency virus (HIV);

12. current treatment for non-tuberculous mycobacterial (NTM) lung disease or
tuberculosis;

13. known or suspected to be allergic or unable to tolerate colistimethate sodium
(intravenous or inhaled) or other polymixins, including evidence of bronchial
hyper-reactivity following inhaled colistimethate sodium;

14. treatment with long term (= 30 days) prednisone at a dose of greater than 15 mg a day
(or equivalent dose of any other corticosteroid) started within six months of the
Screening Visit (Visit 1);

15. new maintenance treatment with any oral macrolides ( (e.g.
azithromycin/erythromycin/clarithromycin) within 30 days of the Screening Visit (Visit
1) or started between Visit 1 and Visit 2;

16. use of any intravenous or intramuscular or oral or inhaled anti-pseudomonal antibiotic
(except chronic macrolides with a stable dose) within 30 days prior to the Screening
Visit (Visit 1) and between Visit 1 and Visit 2;

17. pregnant or breast feeding or plan to become pregnant over the next two years or of
child- bearing potential and unwilling to use a reliable method of contraception for
at least one month before randomisation and throughout their involvement in the trial;

18. significant abnormality in clinical evaluations and/or laboratory tests (physical
examination, vital signs, haematology, clinical chemistry, clinically relevant
impaired renal function, defined as serum creatinine levels =2.0x upper limit of
normal, ECG) endangering the safe participation of the patient in the study at the
Screening Visit (Visit 1) and during the study;

19. participated in another investigational, interventional trial within 30 days prior to
the Screening Visit (Visit 1);

20. in the opinion of the Investigator not suitable for inclusion for whatever reason.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/01/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/03/2022
Sample size
Target
Accrual to date
Final
287
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Zambon Investigative Site - Adelaide
Recruitment hospital [2] 0 0
Zambon investigative site - Concord
Recruitment hospital [3] 0 0
Zambon investigative site - Greenslopes
Recruitment hospital [4] 0 0
Zambon Investigative Site - Kent Town
Recruitment hospital [5] 0 0
Zambon Investigative Site - South Brisbane
Recruitment hospital [6] 0 0
Zambon investigative site - Spearwood
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
2139 - Concord
Recruitment postcode(s) [3] 0 0
4120 - Greenslopes
Recruitment postcode(s) [4] 0 0
5067 - Kent Town
Recruitment postcode(s) [5] 0 0
4101 - South Brisbane
Recruitment postcode(s) [6] 0 0
6163 - Spearwood
Recruitment outside Australia
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Lisboa

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Zambon SpA
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of the trial was to investigate the effect of the use of inhaled
colistimethate sodium (CMS), administered twice a day (b.i.d.) via a specific nebulizer for
12 months, compared to placebo in subjects with non-cystic fibrosis bronchiectasis (NCFB)
chronically infected with P. aeruginosa on the annualised frequency of pulmonary
exacerbations.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03460704
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Paola Castellani, MD
Address 0 0
Zambon S.p.A.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03460704