Prevention of relapses with levamisole as adjuvant therapy in children with a first episode of idiopathic nephrotic syndrome: Study protocol for a double blind, randomised placebo-controlled trial (the LEARNS study)

Floor Veltkamp, Djera H. Khan, Christa Reefman, Susan Veissi, Hedy A. van Oers, Elena Levtchenko, Ron A. A. Mathôt, Sandrine Florquin, Joanna A. E. van Wijk, Michiel F. Schreuder, Lotte Haverman, Antonia H. M. Bouts

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Introduction: Idiopathic nephrotic syndrome (INS) is characterised by a high relapse rate up to 80% after initial response to standard therapy with corticosteroids. Steroid toxicity is common and causes a great burden of disease that negatively influences the health-related quality of life (HRQoL). Recently, studies have shown that levamisole, an anthelminthic drug, significantly improves relapse-free survival in children with frequent relapses or steroid dependency. Compared with other steroid-sparing drugs, levamisole has relatively few side effects. We hypothesise that adding levamisole to standard therapy with corticosteroids in children with a first episode of INS will prevent relapses, decrease cumulative dosage of steroids used and improve HRQoL. This paper presents the study protocol for the LEARNS study (LEvamisole as Adjuvant therapy to Reduce relapses of Nephrotic Syndrome). Methods and analysis: An international, double-blind, placebo-controlled randomised trial will be conducted in 20 participating hospitals in the Netherlands and Belgium. Participants (n=92) with a first episode of INS, aged 2-16 years, who achieve remission after 4 weeks of oral prednisolone will be randomly assigned (1:1) to receive either levamisole 2.5 mg/kg alternate day or placebo added to prednisolone (18-week tapering schedule) for a total of 24 weeks. Follow-up will be until 2 years after first presentation. Additionally, parents and/or children will fill out five HRQoL questionnaires. Primary outcome of the LEARNS study is occurrence of relapses within 12 months after first presentation. Secondary outcomes include time to first relapse, cumulative steroid dose after 2 years, safety parameters and quality of life scores. Ethics and dissemination: The trial was approved by the Medical Ethical Committee. Results of the study will be published in a peer-reviewed journal.
Original languageEnglish
Article numbere027011
JournalBMJ Open
Volume9
Issue number8
DOIs
Publication statusPublished - 2019

Cite this

Veltkamp, Floor ; Khan, Djera H. ; Reefman, Christa ; Veissi, Susan ; van Oers, Hedy A. ; Levtchenko, Elena ; Mathôt, Ron A. A. ; Florquin, Sandrine ; van Wijk, Joanna A. E. ; Schreuder, Michiel F. ; Haverman, Lotte ; Bouts, Antonia H. M. / Prevention of relapses with levamisole as adjuvant therapy in children with a first episode of idiopathic nephrotic syndrome: Study protocol for a double blind, randomised placebo-controlled trial (the LEARNS study). In: BMJ Open. 2019 ; Vol. 9, No. 8.
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title = "Prevention of relapses with levamisole as adjuvant therapy in children with a first episode of idiopathic nephrotic syndrome: Study protocol for a double blind, randomised placebo-controlled trial (the LEARNS study)",
abstract = "Introduction: Idiopathic nephrotic syndrome (INS) is characterised by a high relapse rate up to 80{\%} after initial response to standard therapy with corticosteroids. Steroid toxicity is common and causes a great burden of disease that negatively influences the health-related quality of life (HRQoL). Recently, studies have shown that levamisole, an anthelminthic drug, significantly improves relapse-free survival in children with frequent relapses or steroid dependency. Compared with other steroid-sparing drugs, levamisole has relatively few side effects. We hypothesise that adding levamisole to standard therapy with corticosteroids in children with a first episode of INS will prevent relapses, decrease cumulative dosage of steroids used and improve HRQoL. This paper presents the study protocol for the LEARNS study (LEvamisole as Adjuvant therapy to Reduce relapses of Nephrotic Syndrome). Methods and analysis: An international, double-blind, placebo-controlled randomised trial will be conducted in 20 participating hospitals in the Netherlands and Belgium. Participants (n=92) with a first episode of INS, aged 2-16 years, who achieve remission after 4 weeks of oral prednisolone will be randomly assigned (1:1) to receive either levamisole 2.5 mg/kg alternate day or placebo added to prednisolone (18-week tapering schedule) for a total of 24 weeks. Follow-up will be until 2 years after first presentation. Additionally, parents and/or children will fill out five HRQoL questionnaires. Primary outcome of the LEARNS study is occurrence of relapses within 12 months after first presentation. Secondary outcomes include time to first relapse, cumulative steroid dose after 2 years, safety parameters and quality of life scores. Ethics and dissemination: The trial was approved by the Medical Ethical Committee. Results of the study will be published in a peer-reviewed journal.",
author = "Floor Veltkamp and Khan, {Djera H.} and Christa Reefman and Susan Veissi and {van Oers}, {Hedy A.} and Elena Levtchenko and Math{\^o}t, {Ron A. A.} and Sandrine Florquin and {van Wijk}, {Joanna A. E.} and Schreuder, {Michiel F.} and Lotte Haverman and Bouts, {Antonia H. M.}",
year = "2019",
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language = "English",
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Prevention of relapses with levamisole as adjuvant therapy in children with a first episode of idiopathic nephrotic syndrome: Study protocol for a double blind, randomised placebo-controlled trial (the LEARNS study). / Veltkamp, Floor; Khan, Djera H.; Reefman, Christa; Veissi, Susan; van Oers, Hedy A.; Levtchenko, Elena; Mathôt, Ron A. A.; Florquin, Sandrine; van Wijk, Joanna A. E.; Schreuder, Michiel F.; Haverman, Lotte; Bouts, Antonia H. M.

In: BMJ Open, Vol. 9, No. 8, e027011, 2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Prevention of relapses with levamisole as adjuvant therapy in children with a first episode of idiopathic nephrotic syndrome: Study protocol for a double blind, randomised placebo-controlled trial (the LEARNS study)

AU - Veltkamp, Floor

AU - Khan, Djera H.

AU - Reefman, Christa

AU - Veissi, Susan

AU - van Oers, Hedy A.

AU - Levtchenko, Elena

AU - Mathôt, Ron A. A.

AU - Florquin, Sandrine

AU - van Wijk, Joanna A. E.

AU - Schreuder, Michiel F.

AU - Haverman, Lotte

AU - Bouts, Antonia H. M.

PY - 2019

Y1 - 2019

N2 - Introduction: Idiopathic nephrotic syndrome (INS) is characterised by a high relapse rate up to 80% after initial response to standard therapy with corticosteroids. Steroid toxicity is common and causes a great burden of disease that negatively influences the health-related quality of life (HRQoL). Recently, studies have shown that levamisole, an anthelminthic drug, significantly improves relapse-free survival in children with frequent relapses or steroid dependency. Compared with other steroid-sparing drugs, levamisole has relatively few side effects. We hypothesise that adding levamisole to standard therapy with corticosteroids in children with a first episode of INS will prevent relapses, decrease cumulative dosage of steroids used and improve HRQoL. This paper presents the study protocol for the LEARNS study (LEvamisole as Adjuvant therapy to Reduce relapses of Nephrotic Syndrome). Methods and analysis: An international, double-blind, placebo-controlled randomised trial will be conducted in 20 participating hospitals in the Netherlands and Belgium. Participants (n=92) with a first episode of INS, aged 2-16 years, who achieve remission after 4 weeks of oral prednisolone will be randomly assigned (1:1) to receive either levamisole 2.5 mg/kg alternate day or placebo added to prednisolone (18-week tapering schedule) for a total of 24 weeks. Follow-up will be until 2 years after first presentation. Additionally, parents and/or children will fill out five HRQoL questionnaires. Primary outcome of the LEARNS study is occurrence of relapses within 12 months after first presentation. Secondary outcomes include time to first relapse, cumulative steroid dose after 2 years, safety parameters and quality of life scores. Ethics and dissemination: The trial was approved by the Medical Ethical Committee. Results of the study will be published in a peer-reviewed journal.

AB - Introduction: Idiopathic nephrotic syndrome (INS) is characterised by a high relapse rate up to 80% after initial response to standard therapy with corticosteroids. Steroid toxicity is common and causes a great burden of disease that negatively influences the health-related quality of life (HRQoL). Recently, studies have shown that levamisole, an anthelminthic drug, significantly improves relapse-free survival in children with frequent relapses or steroid dependency. Compared with other steroid-sparing drugs, levamisole has relatively few side effects. We hypothesise that adding levamisole to standard therapy with corticosteroids in children with a first episode of INS will prevent relapses, decrease cumulative dosage of steroids used and improve HRQoL. This paper presents the study protocol for the LEARNS study (LEvamisole as Adjuvant therapy to Reduce relapses of Nephrotic Syndrome). Methods and analysis: An international, double-blind, placebo-controlled randomised trial will be conducted in 20 participating hospitals in the Netherlands and Belgium. Participants (n=92) with a first episode of INS, aged 2-16 years, who achieve remission after 4 weeks of oral prednisolone will be randomly assigned (1:1) to receive either levamisole 2.5 mg/kg alternate day or placebo added to prednisolone (18-week tapering schedule) for a total of 24 weeks. Follow-up will be until 2 years after first presentation. Additionally, parents and/or children will fill out five HRQoL questionnaires. Primary outcome of the LEARNS study is occurrence of relapses within 12 months after first presentation. Secondary outcomes include time to first relapse, cumulative steroid dose after 2 years, safety parameters and quality of life scores. Ethics and dissemination: The trial was approved by the Medical Ethical Committee. Results of the study will be published in a peer-reviewed journal.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/31375606

U2 - 10.1136/bmjopen-2018-027011

DO - 10.1136/bmjopen-2018-027011

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JO - BMJ Open

JF - BMJ Open

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