Clinical trial NCT03093974: Efficacy and Safety of Inhaled CMS in Bronchiectasis Subjects With Chronic P. Aeruginosa Infection. (PROMIS-I)
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non Cystic Fibrosis Bronchiectasis
Keywords: Colistimethate Sodium
CMS
Lead sponsor: Zambon SpA
Sponsor class: INDUSTRY
First posted: 2017-03-28
Enrollment: 377
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The objective of the trial was to investigate the effect of the use of inhaled CMS, administered b.i.d. via a specific nebuliser for 12 months, compared to placebo in subjects with NCFB chronically infected with P. aeruginosa on the annualised frequency of pulmonary exacerbations.

Detailed description: This was a randomised, multi-centre, double-blind, placebo-controlled, parallel group interventional trial in subjects with NCFB and chronic P. aeruginosa infection. Subjects were randomised to CMS or placebo in a 1:1 ratio. The study consisted of seven clinic visits over one year with a follow-up phone call two weeks after discontinuation of treatment. Additional clinic visits, where feasible,and weekly phone calls were conducted during or after pulmonary exacerbations (or any episodes of pneumonia) until resolution.

All planned and unscheduled visits were preferably performed at sites, whenever possible. If on site visits after Visit 2 could not be performed at site due to COVID-19, remote visits (e.g., by telephone) were permitted. Mandatory on site visits were kept for Screening Visit (Visit 1) and Randomisation (Visit 2). If the final visit (Visit 7) had to be conducted remotely, then subjects were asked to return to the clinic for on-site assessments at the earliest opportunity.

Eligibility criteria: 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.

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.

Primary outcomes:
measure: Mean Annual Non-cystic Fibrosis Bronchiectasis (NCFB) Pulmonary Exacerbation Rate
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Zambon Investigative Site
city: Adelaide
country: Australia
facility: Zambon Investigative Site
city: Chermside
country: Australia
facility: Zambon Investigative Site
city: Concord
country: Australia
facility: Zambon Investigative Site
city: Frankston
country: Australia
facility: Zambon Investigative Site
city: Greenslopes
country: Australia
facility: Zambon Investigative Site
city: Melbourne
country: Australia
facility: Zambon Investigative Site
city: Nedlands
country: Australia
facility: Zambon Investigative Site
city: New Lambton Heights
country: Australia
facility: Zambon Investigative Site
city: South Brisbane
country: Australia
facility: Zambon Investigative Site
city: Spearwood
country: Australia
facility: Zambon Investigative Site
city: Westmead
country: Australia
facility: Zambon Investigative Site
city: Gent
country: Belgium
facility: Zambon Investigative Site
city: Roeselare
country: Belgium
facility: Zambon Investigative Site
city: Berlin
country: Germany
facility: Zambon Investigative Site
city: Berlin
country: Germany
facility: Zambon Investigative Site
city: Essen
country: Germany
facility: Zambon Investigative Site
city: Frankfurt am Main
country: Germany
facility: Zambon Investigative Site
city: Frankfurt am Main
country: Germany
facility: Zambon Investigative Site
city: Hamburg
country: Germany
facility: Zambon Investigative Site
city: Hannover
country: Germany
facility: Zambon Investigative Site
city: Lübeck
country: Germany
facility: Zambon Investigative Site
city: Muenchen
country: Germany
facility: Zambon Investigative Site
city: München
country: Germany
facility: Zambon Investigative Site
city: Münster
country: Germany
facility: Zambon Investigative Site
city: Athens
country: Greece
facility: Zambon Investigative Site
city: Haifa
country: Israel
facility: Zambon Investigative Site
city: Jerusalem
country: Israel
facility: Zambon Investigative Site
city: Kfar Saba
country: Israel
facility: Zambon Investigative Site
city: Petah Tikva
country: Israel
facility: Zambon Investigative Site
city: Reẖovot
country: Israel
facility: Zambon Investigative Site
city: Tsrifin
country: Israel
facility: Zambon Investigative Site
city: Orbassano
country: Italy
facility: Zambon Investigative Site
state: TO
city: Bari
country: Italy
facility: Zambon Investigative Site
city: Brescia
country: Italy
facility: Zambon Investigative Site
city: Foggia
country: Italy
facility: Zambon Investigative Site
city: Milano
country: Italy
facility: Zambon Investigative Site
city: Monza
country: Italy
facility: Zambon Investigative Site
city: Palermo
country: Italy
facility: Zambon Investigative Site
city: Palermo
country: Italy
facility: Zambon Investigative Site
city: Pavia
country: Italy
facility: Zambon Investigative Site
city: Pisa
country: Italy
facility: Zambon Investigative Site
city: Roma
country: Italy
facility: Zambon Investigative Site
city: Groningen
country: Netherlands
facility: Zambon Investigative Site
city: Auckland
country: New Zealand
facility: Zambon Investigative Site
city: Auckland
country: New Zealand
facility: Zambon Investigative Site
city: Christchurch
country: New Zealand
facility: Zambon Investigative Site
city: Dunedin
country: New Zealand
facility: Zambon Investigative Site
city: Hamilton West
country: New Zealand
facility: Zambon Investigative Site
city: Aveiro
country: Portugal
facility: Zambon Investigative Site
city: Braga
country: Portugal
facility: Zambon Investigative Site
city: Coimbra
country: Portugal
facility: ZambonInvestigative Site
city: Guimarães
country: Portugal
facility: Zambon Investigative Site
city: Lisboa
country: Portugal
facility: Zambon Investigative site
city: Loures
country: Portugal
facility: Zambon Investigative Site
city: Porto
country: Portugal
facility: Zambon Investigative Site
city: Porto
country: Portugal
facility: Zambon Investigative Site
city: Vila Nova De Gaia
country: Portugal
facility: Zambon Investigative Site
city: A Coruña
country: Spain
facility: Zambon Investigative Site
city: Barcelona
country: Spain
facility: Zambon Investigative Site
city: Barcelona
country: Spain
facility: Zambon Investigative Site
city: Barcelona
country: Spain
facility: Zambon Investigative Site
city: Lleida
country: Spain
facility: Zambon Investigative Site
city: Madrid
country: Spain
facility: Zambon Investigative Site
city: Madrid
country: Spain
facility: Zambon Investigative Site
city: Santander
country: Spain
facility: Zambon Investigative Site
city: Sevilla
country: Spain
facility: Zambon Investigative Site
city: Torrejón de Ardoz
country: Spain
facility: Zambon Investigative Site
city: Usansolo
country: Spain
facility: Zambon Investigative Site
city: Valencia
country: Spain
facility: Zambon Investigative Site
city: Valencia
country: Spain
facility: Zambon Investigative Site
city: Saint Gallen
country: Switzerland
facility: Zambon Investigative Site
city: Cambridge
country: United Kingdom
facility: Zambon Investigative Site
city: Cardiff
country: United Kingdom
facility: Zambon Investigative Site
city: Dundee
country: United Kingdom
facility: Zambon Investigative site
city: Edinburgh
country: United Kingdom
facility: Zambon Investigative Site
city: Gillingham
country: United Kingdom
facility: Zambon Investigative Site
city: Glasgow
country: United Kingdom
facility: Zambon Investigative Site
city: Kirkcaldy
country: United Kingdom
facility: Zambon Investigative Site
city: Liverpool
country: United Kingdom
facility: Zambon Investigational site
city: Llanelli
country: United Kingdom
facility: Zambon Investigative Site
city: London
country: United Kingdom
facility: Zambon Investigative Site
city: Manchester
country: United Kingdom
facility: Zambon investigative Site
city: Newcastle upon Tyne
country: United Kingdom
facility: Zambon Investigative Site
city: Worcester
country: United Kingdom
facility: Zambon Investigative Site
Study officials:
References: