Comparison of the Tolerability of Two Formulations of Hypertonic Saline in Cystic Fibrosis Patients

Study Overview
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Brief Summary
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The purpose of this study is to compare the tolerability and acceptability of a formulation containing Hypertonic saline 7% (HS) alone and a formulation containing HS and Hyaluronic acid 0.1% in a population of Cystic Fibrosis (CF) patients who already showed poor tolerance to HS.

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Other: Inhalable Hypertonic saline 7% + Hyaluronan 0.1%
* Other: Inhalable Hypertonic saline 7%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of Cystic Fibrosis (genotyping and sweat test) > 8 year-old clinically and therapeutically stable disease in the last 30 days; Forced Expiratory Volume in one second (FEV1) ≥ 50% of predicted value; intolerance (cough, throat irritation, saltiness) to previous administration of 5.8% hypertonic saline solution. Exclusion Criteria: decrease in FEV1 >15% after first inhalation of hypertonic saline; Burkholderia cepacia infection; infective exacerbation requiring antibiotic treatment in the 15 days preceding enrolment; patient non compliant to standard therapy; Lung transplant; Patient unable to perform reproducible spirometry; Intolerance to β2 bronchodilators; Concurrent enrolment in other clinical trials; Plasmatic creatinine and transaminases more than twice the normal values.

Ages Eligible for Study
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Minimum Age: 8 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: group A<br> | Other: Inhalable Hypertonic saline 7% + Hyaluronan 0.1%<br>* Administration of Inhalable Hypertonic saline 7% + Hyaluronan 0.1% 5 ml twice a day, after bronchodilator for one month.<br>|
| Experimental: group B<br> | Other: Inhalable Hypertonic saline 7%<br>* Administration of Inhalable Hypertonic saline 7% 5 ml twice a day, after bronchodilator for one month.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the judgement on global pleasure of the inhalation between the two treatment groups | A judgment on acceptability and global pleasure of the inhalation was weekly reported by patients on a diary, expressed on a 1-10 scale: a score lower than 6 was considered unfavourable. | The outcome measure was assessed at day 1, day 7, day 14, day 21, and day 28 of the four-weeks treatment period. For each time-point we operated a comparison between the two groups. | 
| Comparison of the symptom cough between the two treatment groups | A judgement on the symptom cough, one of the most important causes of HS intolerance and poor compliance to HS treatment, was weekly reported by patients on a diary, as assessed on a scale of four grades (absent, mild, moderate, severe). | The outcome measure was assessed at day 1, day 7, day 14, day 21, and day 28 of the four-weeks treatment period. For each time-point we operated a comparison between the two groups. | 
| Comparison of the sensation of saltiness between the two treatment groups | A judgement on the sensation of saltiness, one of the most important causes of HS intolerance and poor compliance to HS treatment, was weekly reported by patients on a diary, as assessed on a scale of four grades (absent, mild, moderate, severe). | The outcome measure was assessed at day 1, day 7, day 14, day 21, and day 28 of the four-weeks treatment period. For each time-point we operated a comparison between the two groups. | 
| Comparison of the sensation of throat irritation between the two treatment groups | A judgement on the sensation of throat irritation, one of the most important causes of HS intolerance and poor compliance to HS treatment, was weekly reported by patients on a diary, as assessed on a scale of four grades (absent, mild, moderate, severe). | The outcome measure was assessed at day 1, day 7, day 14, day 21, and day 28 of the four-weeks treatment period. For each time-point we operated a comparison between the two groups. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Delta FEV1 between the two treatment groups | Secondary outcome was the effect on respiratory function. A sequence of spirometries was performed as follows. A spirometry was performed in basal conditions, then 400 ug of salbutamol were administered and spirometry was performed again after 15 minutes. Whitin 30 minutes, the first dose of the randomized formulation was administered for 15 minutes and a third spirometry was performed 30 minutes after the inhalation. This sequence was repeated 4 weeks later, with the administration of the last dose of treatment. Delta FEV1 was calculated as follows: [(FEV1 after randomized solution inhalation - FEV1 after bronchodilator)/FEV1 after bronchodilator]x 100. Delta FEV1 was the outcome measure used to compare the two groups of treatment both at the first dose of the four-weeks treatment and at the end (last dose)of the four-weeks treatment. | day 1 and day 28 of the four-weeks treatment |