Parameters to Assess Response to Intra-Venous Antibiotic Treatment for Pulmonary Exacerbations in Cystic Fibrosis

Study Overview
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Brief Summary
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Cystic fibrosis (CF) is a multisystem disease characterized by viscid secretions in multiple organ systems. Lung infection and damage account for most of the disease burden. Acute changes in respiratory signs and symptoms termed Pulmonary Exacerbations require treatment with intravenous antibiotics and hospital admission. These episodes cause substantial disruption to people's lives and impact on lung function, quality of life and lifespan. Current treatment regimes require improvement but further study is needed to identify who might benefit from a different approach. This observational study aims to assess if multi-dimensional measurements taken during treatment correspond with later treatment response. This may allow us to personalise treatment more effectively in the future and to better understand how individuals respond to treatment.

Detailed Description
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Pulmonary Exacerbations in CF require treatment with intravenous (IV) antibiotics and hospital admission for between 10-21 days. These episodes cause substantial disruption to people's lives and impact on lung function, quality of life and lifespan.Robust evidence to support current treatment approaches is lacking with awareness that current regimes could be optimised. As yet there is no model for predicting how patients with CF will respond to IV antibiotic treatment- other than clinical judgement and lung function response.This is due to lack of robust measures to identify clinical response at the time of treatment and safely predict later clinical outcomes. The heterogeneity of the 21st Century CF population means a multi-dimensional composite measure is needed. This study has therefore been designed to provide an overall picture of people's response including clinical, biochemical and patient related outcome measures. Using multi-dimensional assessment we hope the measures assessed in this study will give a better picture of how people feel and how they respond to treatment.

Official Title
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Parameters to Assess Response to Intra-Venous Antibiotic Treatment for Pulmonary Exacerbations in Cystic Fibrosis

Conditions
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Cystic Fibrosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients attending the adult service with a confirmed diagnosis of CF by sweat test or genotype Able to provide written informed consent Able to understand and comply with protocol requirements and instructions Confirmed Pulmonary Exacerbation requiring treatment with intravenous antibiotics using defined criteria (Physician and patient agreed need for admission for intravenous antibiotic treatment) Exclusion Criteria: Previous recipient of a lung or other solid organ transplant Inability to complete questionnaires Current enrolment in other investigational medicinal product randomised trial Admission for reasons other than pulmonary exacerbation of CF

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adults with Cystic Fibrosis<br>All Adults with a confirmed diagnosis of Cystic Fibrosis being admitted for Intra-Venous Antibiotic Treatment of a Pulmonary Exacerbation This study is observational so no intervention will be carried out. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Expiratory Volume in 1 second (FEV1) | Lung function Measure | Change in lung function between baseline and day 0, Day 5 and Day 14 of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Failure defined by need for further IV antibiotic treatment within 30 days | The number of participants requiring a further course of IV antibiotics within 30 days | Need for a further course of IV antibiotics within 30 days of treatment completion | 
| Change in Respiratory Symptoms | Change in Respiratory Symptoms assessed by CF-Respiratory Symptom Diary | Change between Day 0, day 5 and day 14 of treatment | 
| Physical activity levels (step count, distance walked, Lightly active minutes, Moderate velocity physical activity (MVPA) and Exercise) | Change in Physical Activity Levels measured by consumable wearable device | Change between Day 0, day 5 and day 14 of treatment | 
| Sleep parameters measured by consumable wearable device | Change in time in bed, time asleep and time awake/restless (mins) | Change between Day 0, day 5 and day 14 of treatment | 
| Change in serum inflammatory marker (C-Reactive Protein) | Change in serum inflammatory marker (CRP) | Change between Day 0, day 5 and day 14 of treatment | 
| Change in sputum inflammatory markers | Change in sputum (Interleukins, Tumour Necrosis Factor-Alpha, Calprotectin and Human Mobility Growth Box Protein -1) inflammatory markers (measured in pg/ml) | Change between Day 0, day 5 and day 14 of treatment | 
| Change in microbiological growth measured by culture | Change in microbiological growth measured by culture | Change between Day 0, day 5 and day 14 of treatment | 
| Change in microbiological community composition measured by microbiota analysis | Change in microbiological relative abundance, dominance, evenness, diversity and richness | Change between Day 0, day 5 and day 14 of treatment | 
| Change in 24 hour sputum volume | Change in 24 hour sputum volume (mls) | Change between Day 0, day 5 and day 14 of treatment | 
| Time to next exacerbation | Time to next exacerbation | Time to next course of intravenous antibiotics within 12 month follow up period (study end) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystic Fibrosis, Pulmonary Exacerbation, Antibiotics, Outcome measures