Snowden, J.A. orcid.org/0000-0001-6819-3476, Hawkey, C., Hind, D. orcid.org/0000-0002-6409-4793 et al. (17 more authors) (2019) Autologous stem cell transplantation in refractory Crohn’s disease – low intensity therapy evaluation (ASTIClite): study protocols for a multicentre, randomised controlled trial and observational follow up study. BMC Gastroenterology, 19 (1). 82. ISSN 1471-230X
Abstract
Background
Intestinal inflammation in Crohn’s disease (CD) is caused by mucosal immune system reactivity to luminal antigen and results in debilitating symptoms, reduced quality of life, impaired work productivity and significant health care costs. Not all patients respond to conventional and biologic therapies, with chronic inflammation ensuing. Although surgical resection may be required, disease frequently returns and surgery may not be an option, or may be declined. Case reports suggest potential benefit after haematopoietic stem cell transplant (HSCT) for patients with refractory CD.
The ASTIC trial asked whether HSCT could cure CD. Few patients achieved the primary endpoint of clinical remission for 3 months, off all medication with no evidence of active disease, and there were a high number of adverse events (AEs) and serious adverse events (SAEs), including one patient death. However, beneficial effects were observed in some aspects of disease activity. The ASTIClite trial will investigate these potential benefits and safety using a lower intensity regimen than ASTIC.
Methods
Ninety-nine participants will be recruited from secondary care IBD centres in the UK into a multicentre, randomised controlled trial (RCT, ASTIClite) and an observational follow-up, and randomised to autologous HSCT versus standard care (ratio 2:1).
The primary endpoint is treatment success at week 48, defined as mucosal healing without surgery or death. Secondary endpoints relating to efficacy, safety and mechanistic analyses will be evaluated at week 8, 14, 24, 32, 40 and 48.
Long-term safety of the low intensity HSCT regimen forms the primary endpoint for the EBMT follow-up study and will be assessed annually for 4–7 years.
Discussion
ASTIClite will compare HSCTlite with standard care with respect to safety, efficacy and quality of life, and capture outcomes allowing findings to be generalised to current clinical practice in the UK. It will also provide significant mechanistic insights into the immunological consequences of HSCTlite and its impact on treatment outcomes. The observational follow-up will provide information, which is currently unavailable for this population.
Trial registration
The ASTIClite RCT was registered on 31st October 2017 (ISRCTN17160440) and the EBMT follow-up study on 19th January 2018 (ISRCTN31981313).
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
Keywords: | Autologous stem cell transplant; Crohn’s disease; Observational study; Randomised controlled trial |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Health and Related Research (Sheffield) > ScHARR - Sheffield Centre for Health and Related Research The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number National Institute for Health Research 15/178/09 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 04 Jul 2019 09:35 |
Last Modified: | 04 Jul 2019 22:19 |
Status: | Published |
Publisher: | BioMed Central |
Refereed: | Yes |
Identification Number: | 10.1186/s12876-019-0992-2 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:147140 |