The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03093974
Ethics application status
Date submitted
9/03/2017
Date registered
28/03/2017
Date last updated
18/02/2019

Titles & IDs
Public title
Long Term Efficacy and Safety of Inhaled Colistimethate Sodium in Bronchiectasis Subjects With Chronic Pseudomonas Aeruginosa Infection.
Scientific title
A Double-blind, Placebo-controlled, Multi-centre, Clinical Trial to Investigate the Efficacy and Safety of 12 Months of Therapy With Inhaled Colistimethate Sodium in the Treatment of Subjects With Non-cystic Fibrosis Bronchiectasis Chronically Infected With Pseudomonas Aeruginosa (P. Aeruginosa)
Secondary ID [1] 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
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
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Colistimethate Sodium
Treatment: Drugs - Saline Solution

Experimental: treatment - Inhaled colistimethate sodium twice daily

Placebo Comparator: Saline solution - inhaled placebo twice daily


Treatment: Drugs: Colistimethate Sodium
1 M units equivalent to 80 mg colistimethate sodium diluted in 1 mL saline solution 0.45%

Treatment: Drugs: Saline Solution
1 ml saline solution 0.45%

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Annualized Pulmonary Exacerbation rate - Annual mean NCFB pulmonary exacerbation rate
Timepoint [1] 0 0
12 months
Secondary outcome [1] 0 0
Time to first pulmonary exacerbation - Time (in days) from the first dose of IMP until the first pulmonary exacerbation;
Timepoint [1] 0 0
12 months
Secondary outcome [2] 0 0
Annualised number of pulmonary exacerbation-free days - Number of exacerbation-free days
Timepoint [2] 0 0
12 months
Secondary outcome [3] 0 0
Number of severe NCFB pulmonary exacerbations, - Severe NCFB pulmonary exacerbations are defined as those requiring intravenous antibiotics and/or hospitalisation;
Timepoint [3] 0 0
12 months
Secondary outcome [4] 0 0
Time to first severe pulmonary exacerbation - Time (in days) from first dose of IMP until the first severe pulmonary exacerbation
Timepoint [4] 0 0
12 months
Secondary outcome [5] 0 0
Quality of life (SGRQ) - Quality of life (QoL) as measured by the total score of the Saint George's Respiratory Questionnaire (SGRQ)
Timepoint [5] 0 0
12 months
Secondary outcome [6] 0 0
Quality of Life (QOL-B) - change from baseline in total score Quality of Life - Bronchiectasis (QOL B) questionnaire
Timepoint [6] 0 0
12 months
Secondary outcome [7] 0 0
Days of work absence - Number of days of work absence due to NCFB pulmonary exacerbations
Timepoint [7] 0 0
12 months
Secondary outcome [8] 0 0
P. aeruginosa density - the mean change in log10 colony forming units (CFU)/g sputum from baseline (Visit 2) to Day 28 of treatment (Visit 3) as well as to Visits 5 (6 months) to 7 (12 months), inclusive
Timepoint [8] 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;

4. had at least 2 NCFB pulmonary exacerbations requiring oral 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 =30% of predicted;

8. had a positive sputum culture for P. aeruginosa from an adequate sample taken at the
Screening Visit (Visit 1).
Minimum age
18 Years
Maximum age
No limit
Gender
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, porphyria or myeloproliferative disease;

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. predominant lung condition being chronic obstructive pulmonary disease (COPD), asthma
or interstitial lung disease in the opinion of the Investigator;

9. respiratory failure requiring long term oxygen therapy or non-invasive ventilation;

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

11. taking immunosuppressive medications (such as azathioprine, methotrexate,
ciclosporine, 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);

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

13. current diagnosis or current treatment for non-tuberculous mycobacterium (NTM)
pulmonary disease or Mycobacterium tuberculosis infection.

14. known to be intolerant to inhaled beta-2 agonists (bronchodilators);

15. 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;

16. 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)

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

18. 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);

19. 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;

20. 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;

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

22. 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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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 - 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 2139 - 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
NSW 2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Bruxelles
Country [2] 0 0
Belgium
State/province [2] 0 0
Roeselare
Country [3] 0 0
Belgium
State/province [3] 0 0
Sint-Niklaas
Country [4] 0 0
Germany
State/province [4] 0 0
Berlin
Country [5] 0 0
Germany
State/province [5] 0 0
Donaustauf
Country [6] 0 0
Germany
State/province [6] 0 0
Essen
Country [7] 0 0
Germany
State/province [7] 0 0
Frankfurt am Main
Country [8] 0 0
Germany
State/province [8] 0 0
Frankfurt
Country [9] 0 0
Germany
State/province [9] 0 0
Hamburg
Country [10] 0 0
Germany
State/province [10] 0 0
Hannover
Country [11] 0 0
Germany
State/province [11] 0 0
Lübeck
Country [12] 0 0
Germany
State/province [12] 0 0
Muenchen
Country [13] 0 0
Germany
State/province [13] 0 0
München
Country [14] 0 0
Germany
State/province [14] 0 0
Münster
Country [15] 0 0
Greece
State/province [15] 0 0
Athens
Country [16] 0 0
Israel
State/province [16] 0 0
Haifa
Country [17] 0 0
Israel
State/province [17] 0 0
Jerusalem
Country [18] 0 0
Israel
State/province [18] 0 0
Kfar Saba
Country [19] 0 0
Israel
State/province [19] 0 0
Petah Tikva
Country [20] 0 0
Israel
State/province [20] 0 0
Re?ovot
Country [21] 0 0
Israel
State/province [21] 0 0
Tsrifin
Country [22] 0 0
Italy
State/province [22] 0 0
TO
Country [23] 0 0
Italy
State/province [23] 0 0
Arezzo
Country [24] 0 0
Italy
State/province [24] 0 0
Brescia
Country [25] 0 0
Italy
State/province [25] 0 0
Cassano Delle Murge
Country [26] 0 0
Italy
State/province [26] 0 0
Foggia
Country [27] 0 0
Italy
State/province [27] 0 0
Monza
Country [28] 0 0
Italy
State/province [28] 0 0
Padova
Country [29] 0 0
Italy
State/province [29] 0 0
Palermo
Country [30] 0 0
Italy
State/province [30] 0 0
Parma
Country [31] 0 0
Italy
State/province [31] 0 0
Pavia
Country [32] 0 0
Italy
State/province [32] 0 0
Pisa
Country [33] 0 0
Italy
State/province [33] 0 0
Roma
Country [34] 0 0
Netherlands
State/province [34] 0 0
Groningen
Country [35] 0 0
New Zealand
State/province [35] 0 0
Auckland
Country [36] 0 0
New Zealand
State/province [36] 0 0
Christchurch
Country [37] 0 0
New Zealand
State/province [37] 0 0
Dunedin
Country [38] 0 0
New Zealand
State/province [38] 0 0
Hamilton West
Country [39] 0 0
Portugal
State/province [39] 0 0
Aveiro
Country [40] 0 0
Portugal
State/province [40] 0 0
Braga
Country [41] 0 0
Portugal
State/province [41] 0 0
Coimbra
Country [42] 0 0
Portugal
State/province [42] 0 0
Creixomil
Country [43] 0 0
Portugal
State/province [43] 0 0
Lisboa
Country [44] 0 0
Portugal
State/province [44] 0 0
Loures
Country [45] 0 0
Portugal
State/province [45] 0 0
Porto
Country [46] 0 0
Portugal
State/province [46] 0 0
Vila Nova De Gaia
Country [47] 0 0
Spain
State/province [47] 0 0
A Coruña
Country [48] 0 0
Spain
State/province [48] 0 0
Barcelona
Country [49] 0 0
Spain
State/province [49] 0 0
Galdakao
Country [50] 0 0
Spain
State/province [50] 0 0
Lleida
Country [51] 0 0
Spain
State/province [51] 0 0
Madrid
Country [52] 0 0
Spain
State/province [52] 0 0
Santander
Country [53] 0 0
Spain
State/province [53] 0 0
Sevilla
Country [54] 0 0
Spain
State/province [54] 0 0
Torrejón de Ardoz
Country [55] 0 0
Spain
State/province [55] 0 0
Valencia
Country [56] 0 0
Switzerland
State/province [56] 0 0
Basel
Country [57] 0 0
Switzerland
State/province [57] 0 0
Saint Gallen
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Cambridge
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Cardiff
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Dundee
Country [61] 0 0
United Kingdom
State/province [61] 0 0
Edinburgh
Country [62] 0 0
United Kingdom
State/province [62] 0 0
Exeter
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Gillingham
Country [64] 0 0
United Kingdom
State/province [64] 0 0
Glasgow
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Kirkcaldy
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Liverpool
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Llanelli
Country [68] 0 0
United Kingdom
State/province [68] 0 0
London
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Newcastle upon Tyne
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Southampton
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Worcester

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

Ethics approval
Ethics application status

Summary
Brief summary
The primary objectives of the trial is to investigate the effect of the use of inhaled
colistimethate sodium, administered twice daily via the I-neb for 12 months, compared to
placebo in subjects with non-cystic fibrosis bronchiectasis (NCFB) chronically infected with
P. aeruginosa on the frequency of pulmonary exacerbations.
Trial website
https://clinicaltrials.gov/show/NCT03093974
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Luca Raiteri, MD
Address 0 0
Zambon SpA
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Michela Meroni, MSc
Address 0 0
Country 0 0
Phone 0 0
+39.02.6652.4208
Fax 0 0
Email 0 0
clinicaltrials@zambongroup.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03093974