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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03093974




Registration number
NCT03093974
Ethics application status
Date submitted
9/03/2017
Date registered
28/03/2017

Titles & IDs
Public title
Efficacy and Safety of Inhaled CMS in Bronchiectasis Subjects With Chronic P. Aeruginosa Infection. (PROMIS-I)
Scientific title
Double-blind, Placebo-controlled, Clinical Trial on Efficacy and Safety of 12-months Therapy With Inhaled Colistimethate Sodium in the Treatment of Subjects With Non-cystic Fibrosis Bronchiectasis Chronically Infected With P. Aeruginosa
Secondary ID [1] 0 0
2015-002743-33
Secondary ID [2] 0 0
Z7224L01
Universal Trial Number (UTN)
Trial acronym
PROMIS-I
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 (Colimesthate 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 International 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 (\~10 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 a period of 12 months.

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 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 maintain 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 participation 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 NCFB 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 Screening Visit (Visit 1) or planned inpatient major surgery during the study period;
6. receiving treatment for allergic bronchopulmonary aspergillosis (ABPA);
7. had 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 previous evidence of bronchial hyperreactivity following inhaled colistimethate sodium;
14. treatment with long term (= 30 days) prednisone at a dose greater than 15 mg a day (or equivalent dose of any other corticosteroid) within six months of the Screening Visit (Visit 1)
15. new maintenance treatment with any oral macrolides (e.g. azithromycin/erythromycin/clarithromycin) started within 30 days of the Screening Visit (Visit 1) and between Visit 1 and Visit 2;
16. use of any intravenous or intramuscular or oral or inhaled antipseudomonal antibiotic (except chronic oral macrolide treatment with a stable dose) within 30 days prior to Screening Visit (Visit 1) and between Visit 1 and Visit 2;
17. pregnant or breast feeding or plan to become pregnant over the next year 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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/06/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/04/2021
Sample size
Target
Accrual to date
Final
377
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Zambon Investigative Site - Adelaide
Recruitment hospital [2] 0 0
Zambon Investigative Site - Chermside
Recruitment hospital [3] 0 0
Zambon Investigative Site - Concord
Recruitment hospital [4] 0 0
Zambon Investigative Site - Frankston
Recruitment hospital [5] 0 0
Zambon Investigative Site - Greenslopes
Recruitment hospital [6] 0 0
Zambon Investigative Site - Melbourne
Recruitment hospital [7] 0 0
Zambon Investigative Site - Nedlands
Recruitment hospital [8] 0 0
Zambon Investigative Site - New Lambton Heights
Recruitment hospital [9] 0 0
Zambon Investigative Site - South Brisbane
Recruitment hospital [10] 0 0
Zambon Investigative Site - Spearwood
Recruitment hospital [11] 0 0
Zambon Investigative Site - Westmead
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
5042 - Adelaide
Recruitment postcode(s) [3] 0 0
4032 - Chermside
Recruitment postcode(s) [4] 0 0
NSW 2134 - Concord
Recruitment postcode(s) [5] 0 0
VIC 3199 - Frankston
Recruitment postcode(s) [6] 0 0
4120 - Greenslopes
Recruitment postcode(s) [7] 0 0
3004 - Melbourne
Recruitment postcode(s) [8] 0 0
WA 6009 - Nedlands
Recruitment postcode(s) [9] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [10] 0 0
4101 - South Brisbane
Recruitment postcode(s) [11] 0 0
6163 - Spearwood
Recruitment postcode(s) [12] 0 0
NSW 2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Gent
Country [2] 0 0
Belgium
State/province [2] 0 0
Roeselare
Country [3] 0 0
Germany
State/province [3] 0 0
Berlin
Country [4] 0 0
Germany
State/province [4] 0 0
Essen
Country [5] 0 0
Germany
State/province [5] 0 0
Frankfurt am Main
Country [6] 0 0
Germany
State/province [6] 0 0
Hamburg
Country [7] 0 0
Germany
State/province [7] 0 0
Hannover
Country [8] 0 0
Germany
State/province [8] 0 0
Lübeck
Country [9] 0 0
Germany
State/province [9] 0 0
Muenchen
Country [10] 0 0
Germany
State/province [10] 0 0
München
Country [11] 0 0
Germany
State/province [11] 0 0
Münster
Country [12] 0 0
Greece
State/province [12] 0 0
Athens
Country [13] 0 0
Israel
State/province [13] 0 0
Haifa
Country [14] 0 0
Israel
State/province [14] 0 0
Jerusalem
Country [15] 0 0
Israel
State/province [15] 0 0
Kfar Saba
Country [16] 0 0
Israel
State/province [16] 0 0
Petah Tikva
Country [17] 0 0
Israel
State/province [17] 0 0
Re?ovot
Country [18] 0 0
Israel
State/province [18] 0 0
Tsrifin
Country [19] 0 0
Italy
State/province [19] 0 0
TO
Country [20] 0 0
Italy
State/province [20] 0 0
Bari
Country [21] 0 0
Italy
State/province [21] 0 0
Brescia
Country [22] 0 0
Italy
State/province [22] 0 0
Foggia
Country [23] 0 0
Italy
State/province [23] 0 0
Milano
Country [24] 0 0
Italy
State/province [24] 0 0
Monza
Country [25] 0 0
Italy
State/province [25] 0 0
Palermo
Country [26] 0 0
Italy
State/province [26] 0 0
Pavia
Country [27] 0 0
Italy
State/province [27] 0 0
Pisa
Country [28] 0 0
Italy
State/province [28] 0 0
Roma
Country [29] 0 0
Netherlands
State/province [29] 0 0
Groningen
Country [30] 0 0
New Zealand
State/province [30] 0 0
Auckland
Country [31] 0 0
New Zealand
State/province [31] 0 0
Christchurch
Country [32] 0 0
New Zealand
State/province [32] 0 0
Dunedin
Country [33] 0 0
New Zealand
State/province [33] 0 0
Hamilton West
Country [34] 0 0
Portugal
State/province [34] 0 0
Aveiro
Country [35] 0 0
Portugal
State/province [35] 0 0
Braga
Country [36] 0 0
Portugal
State/province [36] 0 0
Coimbra
Country [37] 0 0
Portugal
State/province [37] 0 0
Guimarães
Country [38] 0 0
Portugal
State/province [38] 0 0
Lisboa
Country [39] 0 0
Portugal
State/province [39] 0 0
Loures
Country [40] 0 0
Portugal
State/province [40] 0 0
Porto
Country [41] 0 0
Portugal
State/province [41] 0 0
Vila Nova De Gaia
Country [42] 0 0
Spain
State/province [42] 0 0
A Coruña
Country [43] 0 0
Spain
State/province [43] 0 0
Barcelona
Country [44] 0 0
Spain
State/province [44] 0 0
Lleida
Country [45] 0 0
Spain
State/province [45] 0 0
Madrid
Country [46] 0 0
Spain
State/province [46] 0 0
Santander
Country [47] 0 0
Spain
State/province [47] 0 0
Sevilla
Country [48] 0 0
Spain
State/province [48] 0 0
Torrejón de Ardoz
Country [49] 0 0
Spain
State/province [49] 0 0
Usansolo
Country [50] 0 0
Spain
State/province [50] 0 0
Valencia
Country [51] 0 0
Switzerland
State/province [51] 0 0
Saint Gallen
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Cambridge
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Cardiff
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Dundee
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Edinburgh
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Gillingham
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Glasgow
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Kirkcaldy
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Liverpool
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Llanelli
Country [61] 0 0
United Kingdom
State/province [61] 0 0
London
Country [62] 0 0
United Kingdom
State/province [62] 0 0
Manchester
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Newcastle upon Tyne
Country [64] 0 0
United Kingdom
State/province [64] 0 0
Worcester

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03093974