The HAVEN study—hydroxychloroquine in ANCA vasculitis evaluation—a multicentre, randomised, double-blind, placebo-controlled trial: study protocol and statistical analysis plan

on behalf of the HAVEN study group; Annastazia E. Learoyd; Lauren Arnold; Fiona Reid; Nicholas Beckley-Hoelscher; Alina Casian; Shirish Sangle; Neil Morton; Louise Nel; Angela Cape; Susan John; Sangmi Kim; Dharshene Shivapatham; Raashid Luqmani; David Jayne; James Galloway; Abdel Douiri; David D’Cruz

doi:10.1186/s13063-023-07108-3

The HAVEN study—hydroxychloroquine in ANCA vasculitis evaluation—a multicentre, randomised, double-blind, placebo-controlled trial: study protocol and statistical analysis plan

on behalf of the HAVEN study group, Annastazia E. Learoyd^*, Lauren Arnold, Fiona Reid, Nicholas Beckley-Hoelscher, Alina Casian, Shirish Sangle, Neil Morton, Louise Nel, Angela Cape, Susan John, Sangmi Kim, Dharshene Shivapatham, Raashid Luqmani, David Jayne, James Galloway, Abdel Douiri, David D’Cruz

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Patients with non-severe ANCA-associated vasculitis (AAV) are often prescribed immunosuppressive medications that are associated with severe side effects and a reduced quality of life. There is an unmet need for safer effective treatments for these patients. Hydroxychloroquine is being explored due to its effect in similar autoimmune conditions such as systemic lupus erythematosus. Methods: Double-blind, placebo-controlled multicentre trial recruiting 76 patients across 20 sites. Participants will be randomised 1:1 to hydroxychloroquine or placebo in addition to standard of care immunosuppressive therapies over the course of 52 weeks. A phase II selection design will be used to determine hdroxychloroquine’s efficacy, using prednisolone dosage and Birmingham Vasculitis Activity Score as a measure of disease activity. Secondary outcomes will explore other elements of AAV progression, including disease flares and time to remission. Discussion: This trial aims to explore Hydroxychloroquine as a treatment for patients with AAV. If effective, the need for immunosuppressive treatments such as prednisolone could be reduced. Hydroxychloroquine is safer, cheaper and has fewer adverse effects than conventional immunosuppressive treatments. This could improve patient outcomes while saving money for the NHS. Trial registration: ISRCTN: ISRCTN79334891. Registered 07 June 2021. EudraCT: 2018-001268-40. Registered 13 September 2019. Clinicaltrials.gov: NCT04316494. Registered 20 March 2020.

Original language	English
Article number	261
Journal	Trials
Volume	24
Issue number	1
Early online date	6 Apr 2023
DOIs	https://doi.org/10.1186/s13063-023-07108-3
Publication status	E-pub ahead of print - 6 Apr 2023

Keywords

AAV
ANCA
Auto-immune conditions
Hydroxychloroquine
Prednisolone
Vasculitis

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10.1186/s13063-023-07108-3

Cite this

on behalf of the HAVEN study group, Learoyd, A. E., Arnold, L., Reid, F., Beckley-Hoelscher, N., Casian, A., Sangle, S., Morton, N., Nel, L., Cape, A., John, S., Kim, S., Shivapatham, D., Luqmani, R., Jayne, D., Galloway, J., Douiri, A., & D’Cruz, D. (2023). The HAVEN study—hydroxychloroquine in ANCA vasculitis evaluation—a multicentre, randomised, double-blind, placebo-controlled trial: study protocol and statistical analysis plan. Trials, 24(1), [261]. https://doi.org/10.1186/s13063-023-07108-3

@article{1ef65a59b49349a8bb045eb7f6d6ee55,

title = "The HAVEN study—hydroxychloroquine in ANCA vasculitis evaluation—a multicentre, randomised, double-blind, placebo-controlled trial: study protocol and statistical analysis plan",

abstract = "Background: Patients with non-severe ANCA-associated vasculitis (AAV) are often prescribed immunosuppressive medications that are associated with severe side effects and a reduced quality of life. There is an unmet need for safer effective treatments for these patients. Hydroxychloroquine is being explored due to its effect in similar autoimmune conditions such as systemic lupus erythematosus. Methods: Double-blind, placebo-controlled multicentre trial recruiting 76 patients across 20 sites. Participants will be randomised 1:1 to hydroxychloroquine or placebo in addition to standard of care immunosuppressive therapies over the course of 52 weeks. A phase II selection design will be used to determine hdroxychloroquine{\textquoteright}s efficacy, using prednisolone dosage and Birmingham Vasculitis Activity Score as a measure of disease activity. Secondary outcomes will explore other elements of AAV progression, including disease flares and time to remission. Discussion: This trial aims to explore Hydroxychloroquine as a treatment for patients with AAV. If effective, the need for immunosuppressive treatments such as prednisolone could be reduced. Hydroxychloroquine is safer, cheaper and has fewer adverse effects than conventional immunosuppressive treatments. This could improve patient outcomes while saving money for the NHS. Trial registration: ISRCTN: ISRCTN79334891. Registered 07 June 2021. EudraCT: 2018-001268-40. Registered 13 September 2019. Clinicaltrials.gov: NCT04316494. Registered 20 March 2020.",

keywords = "AAV, ANCA, Auto-immune conditions, Hydroxychloroquine, Prednisolone, Vasculitis",

author = "{on behalf of the HAVEN study group} and Learoyd, {Annastazia E.} and Lauren Arnold and Fiona Reid and Nicholas Beckley-Hoelscher and Alina Casian and Shirish Sangle and Neil Morton and Louise Nel and Angela Cape and Susan John and Sangmi Kim and Dharshene Shivapatham and Raashid Luqmani and David Jayne and James Galloway and Abdel Douiri and David D{\textquoteright}Cruz",

note = "Funding Information: This trial is funded by the Medical Research Council (Grant Ref: MR/R006253/1). The funder has had no direct involvement in the trial design or writing of the report nor will they be involved in the analysis, management, interpretation and publication of the data. Funding Information: This research was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust and King{\textquoteright}s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Funding Information: AEL and AD also acknowledge funding support from the NIHR Applied Research Collaboration (ARC) South London at King{\textquoteright}s College Hospital NHS Foundation Trust and the Royal College of Physicians. Funding Information: This research was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust and King{\textquoteright}s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. AEL and AD also acknowledge funding support from the NIHR Applied Research Collaboration (ARC) South London at King{\textquoteright}s College Hospital NHS Foundation Trust and the Royal College of Physicians. We would like to acknowledge all of the members of the research teams at participating sites, as well as the members of the DMC (Professor Ariane Herrick, Professor Caroline Dore and Professor Ed Vital) and TSC (Professor Michael Ehrenstein, Mr Nigel Davies, James Hancocks, Professor Justin Mason, Dr Sanjeev Patel and Dr Gayathri Rajakaruna) for their involvement in the HAVEN trial. We would also like to acknowledge John Mills, chair of the Vasculitis UK charity, and the charity members who helped guide our COVID-19 response. We would also like to thank every patient who has participated in the trial for giving up their time for us. It is intended that the results of the trial will be reported and disseminated at international conferences and in peer-reviewed scientific journals. The chief investigator will ensure that the results are analysed, written up, reported and disseminated upon completion of the trial. Patients recruited to the trial will receive a summarised version of the results at their request. Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = apr,

day = "6",

doi = "10.1186/s13063-023-07108-3",

language = "English",

volume = "24",

journal = "Trials",

issn = "1745-6215",

publisher = "BioMed Central",

number = "1",

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on behalf of the HAVEN study group, Learoyd, AE, Arnold, L, Reid, F, Beckley-Hoelscher, N, Casian, A, Sangle, S, Morton, N, Nel, L, Cape, A, John, S, Kim, S, Shivapatham, D, Luqmani, R, Jayne, D, Galloway, J , Douiri, A & D’Cruz, D 2023, 'The HAVEN study—hydroxychloroquine in ANCA vasculitis evaluation—a multicentre, randomised, double-blind, placebo-controlled trial: study protocol and statistical analysis plan', Trials, vol. 24, no. 1, 261. https://doi.org/10.1186/s13063-023-07108-3

The HAVEN study—hydroxychloroquine in ANCA vasculitis evaluation—a multicentre, randomised, double-blind, placebo-controlled trial : study protocol and statistical analysis plan. / on behalf of the HAVEN study group; Learoyd, Annastazia E.; Arnold, Lauren et al.

In: Trials, Vol. 24, No. 1, 261, 06.04.2023.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - The HAVEN study—hydroxychloroquine in ANCA vasculitis evaluation—a multicentre, randomised, double-blind, placebo-controlled trial

T2 - study protocol and statistical analysis plan

AU - on behalf of the HAVEN study group

AU - Learoyd, Annastazia E.

AU - Arnold, Lauren

AU - Reid, Fiona

AU - Beckley-Hoelscher, Nicholas

AU - Casian, Alina

AU - Sangle, Shirish

AU - Morton, Neil

AU - Nel, Louise

AU - Cape, Angela

AU - John, Susan

AU - Kim, Sangmi

AU - Shivapatham, Dharshene

AU - Luqmani, Raashid

AU - Jayne, David

AU - Galloway, James

AU - Douiri, Abdel

AU - D’Cruz, David

N1 - Funding Information: This trial is funded by the Medical Research Council (Grant Ref: MR/R006253/1). The funder has had no direct involvement in the trial design or writing of the report nor will they be involved in the analysis, management, interpretation and publication of the data. Funding Information: This research was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Funding Information: AEL and AD also acknowledge funding support from the NIHR Applied Research Collaboration (ARC) South London at King’s College Hospital NHS Foundation Trust and the Royal College of Physicians. Funding Information: This research was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. AEL and AD also acknowledge funding support from the NIHR Applied Research Collaboration (ARC) South London at King’s College Hospital NHS Foundation Trust and the Royal College of Physicians. We would like to acknowledge all of the members of the research teams at participating sites, as well as the members of the DMC (Professor Ariane Herrick, Professor Caroline Dore and Professor Ed Vital) and TSC (Professor Michael Ehrenstein, Mr Nigel Davies, James Hancocks, Professor Justin Mason, Dr Sanjeev Patel and Dr Gayathri Rajakaruna) for their involvement in the HAVEN trial. We would also like to acknowledge John Mills, chair of the Vasculitis UK charity, and the charity members who helped guide our COVID-19 response. We would also like to thank every patient who has participated in the trial for giving up their time for us. It is intended that the results of the trial will be reported and disseminated at international conferences and in peer-reviewed scientific journals. The chief investigator will ensure that the results are analysed, written up, reported and disseminated upon completion of the trial. Patients recruited to the trial will receive a summarised version of the results at their request. Publisher Copyright: © 2023, The Author(s).

PY - 2023/4/6

Y1 - 2023/4/6

N2 - Background: Patients with non-severe ANCA-associated vasculitis (AAV) are often prescribed immunosuppressive medications that are associated with severe side effects and a reduced quality of life. There is an unmet need for safer effective treatments for these patients. Hydroxychloroquine is being explored due to its effect in similar autoimmune conditions such as systemic lupus erythematosus. Methods: Double-blind, placebo-controlled multicentre trial recruiting 76 patients across 20 sites. Participants will be randomised 1:1 to hydroxychloroquine or placebo in addition to standard of care immunosuppressive therapies over the course of 52 weeks. A phase II selection design will be used to determine hdroxychloroquine’s efficacy, using prednisolone dosage and Birmingham Vasculitis Activity Score as a measure of disease activity. Secondary outcomes will explore other elements of AAV progression, including disease flares and time to remission. Discussion: This trial aims to explore Hydroxychloroquine as a treatment for patients with AAV. If effective, the need for immunosuppressive treatments such as prednisolone could be reduced. Hydroxychloroquine is safer, cheaper and has fewer adverse effects than conventional immunosuppressive treatments. This could improve patient outcomes while saving money for the NHS. Trial registration: ISRCTN: ISRCTN79334891. Registered 07 June 2021. EudraCT: 2018-001268-40. Registered 13 September 2019. Clinicaltrials.gov: NCT04316494. Registered 20 March 2020.

AB - Background: Patients with non-severe ANCA-associated vasculitis (AAV) are often prescribed immunosuppressive medications that are associated with severe side effects and a reduced quality of life. There is an unmet need for safer effective treatments for these patients. Hydroxychloroquine is being explored due to its effect in similar autoimmune conditions such as systemic lupus erythematosus. Methods: Double-blind, placebo-controlled multicentre trial recruiting 76 patients across 20 sites. Participants will be randomised 1:1 to hydroxychloroquine or placebo in addition to standard of care immunosuppressive therapies over the course of 52 weeks. A phase II selection design will be used to determine hdroxychloroquine’s efficacy, using prednisolone dosage and Birmingham Vasculitis Activity Score as a measure of disease activity. Secondary outcomes will explore other elements of AAV progression, including disease flares and time to remission. Discussion: This trial aims to explore Hydroxychloroquine as a treatment for patients with AAV. If effective, the need for immunosuppressive treatments such as prednisolone could be reduced. Hydroxychloroquine is safer, cheaper and has fewer adverse effects than conventional immunosuppressive treatments. This could improve patient outcomes while saving money for the NHS. Trial registration: ISRCTN: ISRCTN79334891. Registered 07 June 2021. EudraCT: 2018-001268-40. Registered 13 September 2019. Clinicaltrials.gov: NCT04316494. Registered 20 March 2020.

KW - AAV

KW - ANCA

KW - Auto-immune conditions

KW - Hydroxychloroquine

KW - Prednisolone

KW - Vasculitis

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U2 - 10.1186/s13063-023-07108-3

DO - 10.1186/s13063-023-07108-3

M3 - Article

C2 - 37024906

AN - SCOPUS:85151893355

SN - 1745-6215

VL - 24

JO - Trials

JF - Trials

IS - 1

M1 - 261

ER -

The HAVEN study—hydroxychloroquine in ANCA vasculitis evaluation—a multicentre, randomised, double-blind, placebo-controlled trial: study protocol and statistical analysis plan

Abstract

Keywords

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