Wessex Asthma Cohort of Difficult Asthma

NCT ID: NCT03996590

Last Updated: 2024-01-19

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 566 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-04-22
• Study Completion Date: 2050-12-31

Brief Summary

Asthma is now widely recognised to be a heterogeneous disease. The last two decades have seen the identification of a number of biological targets and development of various novel therapies. Despite this, asthma still represents a significant health and economic burden worldwide. Why some individuals should continue to suffer remains unclear.

The Wessex Asthma Cohort of Difficult Asthma (WATCH) is an ongoing 'real-life', prospective study of patients in the University Hospital Southampton Foundation Trust (UHSFT) Difficult Asthma service. Research data capture is aligned with the extensive clinical characterisation required of a commissioned National Health Service (NHS) Specialist Centre for Severe Asthma. Data acquisition includes detailed clinical, health and disease-related questionnaires, anthropometry, allergy and lung function testing, radiological imaging (in a small subset) and collection of biological samples (blood, urine and sputum). Prospective data are captured in parallel to clinical follow up appointments, with data entered into a bespoke database.

The pragmatic ongoing nature of the WATCH study allows comprehensive assessment of the real world clinical spectrum seen in a Specialist Asthma Centre and allows a longitudinal perspective of deeply phenotyped patients. It is anticipated that the WATCH cohort would act as a vehicle for potential collaborative asthma studies and will build upon our understanding of mechanisms underlying difficult asthma.

Detailed Description

Asthma is estimated to affect 5.2 million people in the United Kingdom (UK), half of whom experience severe symptoms at some point in their lives, and 500,000 of whom may be unresponsive to currently available therapies (Asthma UK; "living on a knife edge" 2004). Severe Asthma probably accounts for 80% of asthma-related health expenditure (Chung KF, Eur Res Mon 2003, 23: 313). In this regard it is estimated to directly cost the NHS (National Health Service) £1 billion per year but also poses considerable hidden societal costs through disability, missed schooling and lost work days.

While Severe Asthma is a significant health-economic problem, the availability of effective treatments in clinical practice remains limited. However there is a growing realisation of the heterogeneity of asthma, which is not a single condition, but composed of numerous potential phenotypes (Wenzel S Nat Med 2012 18(5):716-25) some of which may show association to more severe disease status. In this regard recent adoption of unbiased statistical techniques such as cluster analysis has consistently demonstrated presence of severe asthma clusters in both adult and paediatric populations. These clinical phenotypes may show specific pathophysiological associations leading to classification of endotypes. Accompanying this growing understanding of the diverse nature of asthma is the realisation that there are also a diverse range of treatment responses dependent on the underlying nature of an individual's disease. This naturally leads to the concept of personalised therapy regimes for patients with Severe Asthma that better target their individual disease. Omalizumab is the first biological asthma treatment to meet that need in patients with severe allergic asthma. Numerous potential biological agents are in development that show promise in targeting patients with particular disease phenotypes/ endotypes such as mepolizumab, lebrikizumab and dupilimumab.

The organisation of Clinical Services for Severe Asthma is undergoing major change with the initiation of Specialised Commissioning of such Services by NHS England in 2014. A core requirement for Specialist Centres being Commissioned under this process will be the maintenance of accurate clinical disease registers which link to the BTS Difficult Asthma Registry and support collaborative research studies in the future.

The Difficult Asthma Clinics at Southampton and Portsmouth currently care for 1000 and 400 patients with problematic disease respectively. The two asthma services already collaborate as the Wessex Asthma Network to provide education across the Wessex region. Both services in their roles as Commissioned Specialist Clinical Centre for Severe Asthma receive regional referrals from a wide geographical area. We intend to initiate a comprehensively assessed Difficult Asthma Cohort by inviting all patients in our clinics to participate and contribute data gained through their clinical assessment. This would support ongoing contribution to research via the BTS Difficult Asthma Registry. In addition, a real-life clinical characterisation of Difficult Asthma would provide the basis for a better understanding of the nature of that disease relevant to clinical practice. It would also provide opportunity to develop a better endotype defined understanding of Difficult Asthma that facilitates stratified development of more effective treatment strategies. The Cohort will become a resource for future therapeutic studies in Difficult Asthma with Cohort participants being invited to consent separately into those studies based upon their characterisation through the Cohort.

Conditions

Asthma

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• All patients referred to the Adult or Transitional Regional Asthma Clinics at participating hospitals.
• On high-dose therapies, with or without the addition of continuous or frequent use of oral steroids (or steroid sparing therapies), as defined by the BTS (British Thoracic Society) Adult Asthma Management Guidelines (2016).

Exclusion Criteria

• Asthma patients who are not referred to the Adult or Transitional Regional Asthma Clinics at participating hospitals.
• Any patients who are not on high-dose therapies, with or without the addition of continuous or frequent use of oral steroids (or steroid sparing therapies), as per the BTS (British Thoracic Society) Adult Asthma Management Guidelines (2016).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

Boehringer Ingelheim

INDUSTRY

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Owlstone Ltd

INDUSTRY

Sponsor Role: collaborator

National Institute for Health Research, United Kingdom

OTHER_GOV

Sponsor Role: collaborator

University Hospital Southampton NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ramesh J Kurukulaaratchy, DM FRCP

Role: PRINCIPAL_INVESTIGATOR

University Hospital Southampton NHS Foundation Trust

Locations

Portsmouth Hospitals NHS Trust

Portsmouth, Hamsphire, United Kingdom

University Hospital Southampton NHS Foundation Trust

Southampton, Hamsphire, United Kingdom

Isle of Wight NHS Trust

Newport, Isle Of Wight, United Kingdom

Countries

United Kingdom

References

Smith DH, Malone DC, Lawson KA, Okamoto LJ, Battista C, Saunders WB. A national estimate of the economic costs of asthma. Am J Respir Crit Care Med. 1997 Sep;156(3 Pt 1):787-93. doi: 10.1164/ajrccm.156.3.9611072.

Reference Type: BACKGROUND

PMID: 9309994 (View on PubMed)

Barnes PJ, Jonsson B, Klim JB. The costs of asthma. Eur Respir J. 1996 Apr;9(4):636-42. doi: 10.1183/09031936.96.09040636.

Reference Type: BACKGROUND

PMID: 8726924 (View on PubMed)

Masoli M, Fabian D, Holt S, Beasley R; Global Initiative for Asthma (GINA) Program. The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy. 2004 May;59(5):469-78. doi: 10.1111/j.1398-9995.2004.00526.x. No abstract available.

Reference Type: BACKGROUND

PMID: 15080825 (View on PubMed)

Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med. 2012 May 4;18(5):716-25. doi: 10.1038/nm.2678.

Reference Type: BACKGROUND

PMID: 22561835 (View on PubMed)

Moore WC, Meyers DA, Wenzel SE, Teague WG, Li H, Li X, D'Agostino R Jr, Castro M, Curran-Everett D, Fitzpatrick AM, Gaston B, Jarjour NN, Sorkness R, Calhoun WJ, Chung KF, Comhair SA, Dweik RA, Israel E, Peters SP, Busse WW, Erzurum SC, Bleecker ER; National Heart, Lung, and Blood Institute's Severe Asthma Research Program. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med. 2010 Feb 15;181(4):315-23. doi: 10.1164/rccm.200906-0896OC. Epub 2009 Nov 5.

Reference Type: BACKGROUND

PMID: 19892860 (View on PubMed)

Haldar P, Pavord ID, Shaw DE, Berry MA, Thomas M, Brightling CE, Wardlaw AJ, Green RH. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med. 2008 Aug 1;178(3):218-224. doi: 10.1164/rccm.200711-1754OC. Epub 2008 May 14.

Reference Type: BACKGROUND

PMID: 18480428 (View on PubMed)

Weatherall M, Travers J, Shirtcliffe PM, Marsh SE, Williams MV, Nowitz MR, Aldington S, Beasley R. Distinct clinical phenotypes of airways disease defined by cluster analysis. Eur Respir J. 2009 Oct;34(4):812-8. doi: 10.1183/09031936.00174408. Epub 2009 Apr 8.

Reference Type: BACKGROUND

PMID: 19357143 (View on PubMed)

Fitzpatrick AM, Teague WG, Meyers DA, Peters SP, Li X, Li H, Wenzel SE, Aujla S, Castro M, Bacharier LB, Gaston BM, Bleecker ER, Moore WC; National Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program. Heterogeneity of severe asthma in childhood: confirmation by cluster analysis of children in the National Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program. J Allergy Clin Immunol. 2011 Feb;127(2):382-389.e1-13. doi: 10.1016/j.jaci.2010.11.015. Epub 2010 Dec 31.

Reference Type: BACKGROUND

PMID: 21195471 (View on PubMed)

Just J, Gouvis-Echraghi R, Rouve S, Wanin S, Moreau D, Annesi-Maesano I. Two novel, severe asthma phenotypes identified during childhood using a clustering approach. Eur Respir J. 2012 Jul;40(1):55-60. doi: 10.1183/09031936.00123411. Epub 2012 Jan 20.

Reference Type: BACKGROUND

PMID: 22267763 (View on PubMed)

Lotvall J, Akdis CA, Bacharier LB, Bjermer L, Casale TB, Custovic A, Lemanske RF Jr, Wardlaw AJ, Wenzel SE, Greenberger PA. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol. 2011 Feb;127(2):355-60. doi: 10.1016/j.jaci.2010.11.037.

Reference Type: BACKGROUND

PMID: 21281866 (View on PubMed)

Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, Ortega H, Chanez P. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012 Aug 18;380(9842):651-9. doi: 10.1016/S0140-6736(12)60988-X.

Reference Type: BACKGROUND

PMID: 22901886 (View on PubMed)

Corren J, Lemanske RF, Hanania NA, Korenblat PE, Parsey MV, Arron JR, Harris JM, Scheerens H, Wu LC, Su Z, Mosesova S, Eisner MD, Bohen SP, Matthews JG. Lebrikizumab treatment in adults with asthma. N Engl J Med. 2011 Sep 22;365(12):1088-98. doi: 10.1056/NEJMoa1106469. Epub 2011 Aug 3.

Reference Type: BACKGROUND

PMID: 21812663 (View on PubMed)

Wenzel S, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, Wang L, Kirkesseli S, Rocklin R, Bock B, Hamilton J, Ming JE, Radin A, Stahl N, Yancopoulos GD, Graham N, Pirozzi G. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013 Jun 27;368(26):2455-66. doi: 10.1056/NEJMoa1304048. Epub 2013 May 21.

Reference Type: BACKGROUND

PMID: 23688323 (View on PubMed)

Mistry H, Ajsivinac Soberanis HM, Kyyaly MA, Azim A, Barber C, Knight D, Newell C, Haitchi HM, Wilkinson T, Howarth P, Seumois G, Vijayanand P, Arshad SH, Kurukulaaratchy RJ. The Clinical Implications of Aspergillus Fumigatus Sensitization in Difficult-To-Treat Asthma Patients. J Allergy Clin Immunol Pract. 2021 Dec;9(12):4254-4267.e10. doi: 10.1016/j.jaip.2021.08.038. Epub 2021 Sep 14.

Reference Type: DERIVED

PMID: 34534722 (View on PubMed)

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Document Type: Informed Consent Form

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Other Identifiers

RHM MED1216

Identifier Type: -

Identifier Source: org_study_id