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

Cystic Fibrosis Clinical Trial

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Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04016571
• Other study ID #: IRAS 210802
• Status: Completed
• Start date: December 1, 2016
• Est. completion date: March 1, 2019

Study information

• Verified date: August 2020
• Source: Belfast Health and Social Care Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: March 1, 2019
• Est. primary completion date: August 10, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Locations

Country	Name	City	State
United Kingdom	Belfast Regional Adult CF Centre	Belfast

Sponsors (2)

Lead Sponsor	Collaborator
Belfast Health and Social Care Trust	Queen's University, Belfast

Country where clinical trial is conducted

United Kingdom, 

References & Publications (13)

Britto MT, Kotagal UR, Hornung RW, Atherton HD, Tsevat J, Wilmott RW. Impact of recent pulmonary exacerbations on quality of life in patients with cystic fibrosis. Chest. 2002 Jan;121(1):64-72. — View Citation

Collaco JM, Green DM, Cutting GR, Naughton KM, Mogayzel PJ Jr. Location and duration of treatment of cystic fibrosis respiratory exacerbations do not affect outcomes. Am J Respir Crit Care Med. 2010 Nov 1;182(9):1137-43. doi: 10.1164/rccm.201001-0057OC. Epub 2010 Jun 25. — View Citation

de Boer K, Vandemheen KL, Tullis E, Doucette S, Fergusson D, Freitag A, Paterson N, Jackson M, Lougheed MD, Kumar V, Aaron SD. Exacerbation frequency and clinical outcomes in adult patients with cystic fibrosis. Thorax. 2011 Aug;66(8):680-5. doi: 10.1136/thx.2011.161117. Epub 2011 Jun 15. — View Citation

Flume PA, Mogayzel PJ Jr, Robinson KA, Goss CH, Rosenblatt RL, Kuhn RJ, Marshall BC; Clinical Practice Guidelines for Pulmonary Therapies Committee. Cystic fibrosis pulmonary guidelines: treatment of pulmonary exacerbations. Am J Respir Crit Care Med. 2009 Nov 1;180(9):802-8. doi: 10.1164/rccm.200812-1845PP. Epub 2009 Sep 3. Review. — View Citation

Goss CH, Edwards TC, Ramsey BW, Aitken ML, Patrick DL. Patient-reported respiratory symptoms in cystic fibrosis. J Cyst Fibros. 2009 Jul;8(4):245-52. doi: 10.1016/j.jcf.2009.04.003. Epub 2009 May 29. — View Citation

Heltshe SL, Goss CH, Thompson V, Sagel SD, Sanders DB, Marshall BC, Flume PA. Short-term and long-term response to pulmonary exacerbation treatment in cystic fibrosis. Thorax. 2016 Mar;71(3):223-9. doi: 10.1136/thoraxjnl-2014-206750. Epub 2015 Apr 24. — View Citation

Heltshe SL, Goss CH. Optimising treatment of CF pulmonary exacerbation: a tough nut to crack. Thorax. 2016 Feb;71(2):101-2. doi: 10.1136/thoraxjnl-2015-208057. — View Citation

McCourt F, O'Neill B, Logan I, Abbott J, Plant B, McCrum-Gardner E, McKeown S, Stuart Elborn J, Bradley JM. Indicators of pulmonary exacerbation in cystic fibrosis: A Delphi survey of patients and health professionals. J Cyst Fibros. 2015 Jan;14(1):90-6. doi: 10.1016/j.jcf.2014.06.007. Epub 2014 Aug 12. — View Citation

Sanders DB, Bittner RC, Rosenfeld M, Hoffman LR, Redding GJ, Goss CH. Failure to recover to baseline pulmonary function after cystic fibrosis pulmonary exacerbation. Am J Respir Crit Care Med. 2010 Sep 1;182(5):627-32. doi: 10.1164/rccm.200909-1421OC. Epub 2010 May 12. — View Citation

Shoki AH, Mayer-Hamblett N, Wilcox PG, Sin DD, Quon BS. Systematic review of blood biomarkers in cystic fibrosis pulmonary exacerbations. Chest. 2013 Nov;144(5):1659-1670. doi: 10.1378/chest.13-0693. Review. — View Citation

Smith DJ, Badrick AC, Zakrzewski M, Krause L, Bell SC, Anderson GJ, Reid DW. Pyrosequencing reveals transient cystic fibrosis lung microbiome changes with intravenous antibiotics. Eur Respir J. 2014 Oct;44(4):922-30. doi: 10.1183/09031936.00203013. Epub 2014 Jul 17. — View Citation

VanDevanter DR, O'Riordan MA, Blumer JL, Konstan MW. Assessing time to pulmonary function benefit following antibiotic treatment of acute cystic fibrosis exacerbations. Respir Res. 2010 Oct 6;11:137. doi: 10.1186/1465-9921-11-137. — View Citation

VanDevanter DR, Pasta DJ, Konstan MW. Treatment and demographic factors affecting time to next pulmonary exacerbation in cystic fibrosis. J Cyst Fibros. 2015 Nov;14(6):763-9. doi: 10.1016/j.jcf.2015.02.007. Epub 2015 Mar 6. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change in 24 hour sputum volume	Change in 24 hour sputum volume (mls)	Change between Day 0, day 5 and day 14 of treatment
Secondary	Time to next exacerbation	Time to next exacerbation	Time to next course of intravenous antibiotics within 12 month follow up period (study end)