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

Completed

• Conditions: Cystic Fibrosis

• Registration Number: NCT04016571
• Lead Sponsor: Belfast Health and Social Care Trust

Brief Summary

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

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.

Study Timeline

• Study Start: 2016-12-01
• Primary Completion: 2018-08-10
• Study First Submitted: 2019-01-18
• Study Completion: 2019-03-01
• Study First Submitted QC: 2019-07-10
• Study First Posted: 2019-07-11
• Status Verified: 2020-08
• Last Update Submitted: 2020-08-04
• Last Update Posted: 2020-08-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 31

Inclusion Criteria

1. Patients attending the adult service with a confirmed diagnosis of CF by sweat test or genotype
2. Able to provide written informed consent
3. Able to understand and comply with protocol requirements and instructions
4. Confirmed Pulmonary Exacerbation requiring treatment with intravenous antibiotics using defined criteria (Physician and patient agreed need for admission for intravenous antibiotic treatment)

Exclusion Criteria

1. Previous recipient of a lung or other solid organ transplant
2. Inability to complete questionnaires
3. Current enrolment in other investigational medicinal product randomised trial
4. Admission for reasons other than pulmonary exacerbation of CF

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Forced Expiratory Volume in 1 second (FEV1)	Change in lung function between baseline and day 0, Day 5 and Day 14 of treatment	Lung function Measure

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Belfast Regional Adult CF Centre; 🇬🇧 Belfast, United Kingdom