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Combined Dry Powder Tobramycin and Nebulized Colistin Inhalation in CF Patients (CotoCFII)

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 evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03341741
Recruitment Status : Completed
First Posted : November 14, 2017
Last Update Posted : November 14, 2017
Sponsor:
Information provided by (Responsible Party):
University Hospital Tuebingen

Tracking Information
First Submitted Date  ICMJE November 3, 2017
First Posted Date  ICMJE November 14, 2017
Last Update Posted Date November 14, 2017
Actual Study Start Date  ICMJE March 11, 2014
Actual Primary Completion Date December 19, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 8, 2017)
Amount of P. aeruginosa in sputum [ Time Frame: 30 days ]
The primary endpoint will be the difference of P. aeruginosa cfu/ml in sputum with combined therapy with Tobramycin/Colistin compared to colistin mono-therapy. The analysis will be adjusted for baseline values of each cycle and parametric (paired t-Test) or non-parametric (sign test) methods will be used as appropriate.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: November 8, 2017)
  • Course of P.aeruginosa amount in sputum [ Time Frame: 112 days ]
    Course of P. aeruginosa in sputum measured as cfu/ml during the study
  • Course of forced vital capacity (FVC) absolute amount [ Time Frame: 112 days ]
    Course of FVC absolute in litres during the study
  • Course of FVC relative amount [ Time Frame: 112 days ]
    Course of FVC relative (percent of expected amount for given body height and gender) during the study
  • Course of FEV1 absolute amount [ Time Frame: 112 days ]
    Course of FEV1 absolute in litres during the study
  • Course of FEV1 relative amount [ Time Frame: 112 days ]
    Course of FEV1 relative (percent of expected amount for given body height and gender) during the study
  • Course of MEF25-75 absolute amount [ Time Frame: 112 days ]
    Course of MEF25-75 absolute in litres during the study
  • Course of MEF25-75 relative amount [ Time Frame: 112 days ]
    Course of MEF25-75 relative (percent of expected amount for given body height and gender) during the study
  • Course of proinflammatory cytokine IL1ß amount [ Time Frame: 112 days ]
    Course of proinflammatory cytokine IL1ß amount in sputum [pg/ml] during the study
  • Course of proinflammatory cytokine IL6 amount [ Time Frame: 112 days ]
    Course of proinflammatory cytokine IL6 amount in sputum [pg/ml] during the study
  • Course of proinflammatory cytokine IL8 amount [ Time Frame: 112 days ]
    Course of proinflammatory cytokine IL8 amount in sputum [pg/ml] during the study
  • Course of antiinflammatory cytokine IL10 amount [ Time Frame: 112 days ]
    Course of antiinflammatory cytokine IL10 amount in sputum [pg/ml] during the study
  • Course of proinflammatory cytokine TNFa amount [ Time Frame: 112 days ]
    Course of proinflammatory cytokine TNFa amount in sputum [pg/ml] during the study
  • Course of proinflammatory cytokine GM-CSF amount [ Time Frame: 112 days ]
    Course of proinflammatory cytokine GM-CSF amount in sputum [pg/ml] during the study
  • Course of DNA amount in sputum [ Time Frame: 112 days ]
    Course of DNA amount {pg/ml] in sputum during the study
  • Course of leukocyte amount in sputum [ Time Frame: 112 days ]
    Course of leukocyte amount [pg/ml] in sputum during the study
  • Exacerbation [ Time Frame: 112 days ]
    Number of exacerbations during the study
  • Antibiotics [ Time Frame: 112 days ]
    Use of antibiotics during the study
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combined Dry Powder Tobramycin and Nebulized Colistin Inhalation in CF Patients
Official Title  ICMJE Combined Dry Powder Tobramycin and Nebulized Colistin Inhalation in CF Patients
Brief Summary To assess whether the inhalative combination of Tobramycin/Colistin is more effective in reducing Pseudomonas colony forming units (CFUs) and improvement of lung function than Colistin in mono-therapy.
Detailed Description

Cystic fibrosis (CF), the most common autosomal recessive disorder in Western countries, is caused by mutations of the cystic fibrosis transmembrane conductance regulator molecule (CFTR) and affects approximately 40.000 patients in Europe. The majority of CF patients develop chronic pulmonary infections with Pseudomonas aeruginosa. These are normally treated with single antibiotics, administered orally, intravenously or inhalatively. Once the infection becomes chronic, eradication of the pathogen is not any more possible due to biofilm formation of the pathogen and increasing resistance. However, inhalative antibiotic combination therapy might be more efficient than single antibiotic therapy in chronically infected CF patients. This notion is supported by previous in vitro and animal studies using Tobramycin/Colistin combination therapy. Importantly, a pilot study in five CF patients who inhaled consecutively Colistin and Tobramycin solutions for 4 week, revealed a decrease of log10 2.52 ± 2.5 cfu of P. aeruginosa in sputum specimens during the course of the treatment compared to baseline values (p=0.027). The treatment was shown to be safe and well tolerated. However, forced expiratory volume in 1 sec (FEV1) did not differ significantly.

Taking advantage of the new development of dry powder inhalation (DPI) antibiotics, specifically TOBI© Podhaler, a larger randomised trial has been performed in which the combined TOBI© Podhaler and Colistin treatment is compared to the monotherapy with Colistin.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
randomized, open label clinical study
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cystic Fibrosis With Pulmonary Manifestations
Intervention  ICMJE
  • Drug: Tobramycin Powder
    TOBI®Podhaler 2 x 112 mg daily for 2 x 28 days (on/off);
    Other Name: TOBI®Podhaler
  • Drug: Colistin
    Colistin solution 2 x daily 1 Mega continuously
    Other Name: Colistin solution
Study Arms  ICMJE
  • Experimental: Tobramycin powder / Colistin
    TOBI®Podhaler 2 x 112 mg daily for 2 x 28 days (on/off); and Colistin solution 2 x daily 1 Mega continuously for 112 days
    Interventions:
    • Drug: Tobramycin Powder
    • Drug: Colistin
  • Active Comparator: Colistin
    Colistin solution 2 x daily 1 Mega continuously for at least 30 days
    Intervention: Drug: Colistin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 8, 2017)
26
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 25, 2016
Actual Primary Completion Date December 19, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Cystic Fibrosis is verified;
  2. Patient is 12 years or older;
  3. FEV1 is higher than 25% and lower than 100%;
  4. The patients' lung is colonised with P. aeruginosa chronically (≥6 months);
  5. P. aeruginosa must be sensitive for Tobramycin or Colistin;
  6. Pretreated with Colistin >2 months;
  7. Last i.v. antibiotic treatment ≥2 weeks;
  8. Informed consent is given by patients/legal representatives

Exclusion Criteria:

  1. Clinical deterioration is present (exacerbation symptoms);
  2. Last Tobramycin inhalation treatment ≤ 2 weeks;
  3. Renal dysfunction (creatinine <1.5 fold of normal, glomerular filtration rate (GFR) <80%) at baseline
  4. auditoria or vestibular dysfunction, hearing loss
  5. Intolerances against Tobramycin, Colistin or Polymyxin B
  6. Myasthenia gravis
  7. Porphyria
  8. Pregnancy and nursing
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03341741
Other Study ID Numbers  ICMJE Coto V3.0
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party University Hospital Tuebingen
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University Hospital Tuebingen
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University Hospital Tuebingen
Verification Date October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP