Please use this identifier to cite or link to this item: http://cmuir.cmu.ac.th/jspui/handle/6653943832/76954
Title: ODYSSEY clinical trial design: a randomised global study to evaluate the efficacy and safety of dolutegravir-based antiretroviral therapy in HIV-positive children, with nested pharmacokinetic sub-studies to evaluate pragmatic WHO-weight-band based dolutegravir dosing
Authors: Cecilia L. Moore
Anna Turkova
Hilda Mujuru
Adeodata Kekitiinwa
Abbas Lugemwa
Cissy M. Kityo
Linda N. Barlow-Mosha
Tim R. Cressey
Avy Violari
Ebrahim Variava
Mark F. Cotton
Moherndran Archary
Alexandra Compagnucci
Thanyawee Puthanakit
Osee Behuhuma
Yacine Saϊdi
James Hakim
Pauline Amuge
Lorna Atwine
Victor Musiime
David M. Burger
Clare Shakeshaft
Carlo Giaquinto
Pablo Rojo
Diana M. Gibb
Deborah Ford
Shabinah Ali
Abdel Babiker
Chiara Borg
Anne Marie Borges Da Silva
Joanna Calvert
Joshua Gasa
Nasir Jamil
Sarah Lensen
Emma Little
Fatima Mohamed
Samuel Montero
Cecilia L. Moore
Rachel Oguntimehin
Anna Parker
Reena Patel
Tasmin Phillips
Tatiana Sarfati
Karen Scott
Moira Spyer
Margaret Thomason
Rebecca Turner
Nadine Van Looy
Ellen White
Kaya Widuch
Helen Wilkes
Ben Wynne
Tiziana Grossele
Daniel Gomez-Pena
Davide Bilardi
Giulio Vecchia
Yacine Saidi
Yoann Riault
Alexandra Coelho
Laura Picault
Christelle Kouakam
Suwalai Chalermpantmetagul
Dujrudee Chinwong
Gonzague Jourdain
Rukchanok Peongjakta
Pra ornsuda Sukrakanchana
Wasna Sirirungsi
Janet Seeley
Sarah Bernays
Magda Conway
Nigel Klein
Eleni Nastouli
Anita De Rossi
Maria Angeles Munoz Fernandez
David Burger
Pauline Bollen
Angela Colbers
Hylke Waalewijn
Elizabeth Kaudha
Annet Nanduudu
Emmanuel Mujyambere
Paul Ocitti Labeja
Charity Nankunda
Juliet Ategeka
Peter Erim
Collin Makanga
Esther Nambi
Edridah Keminyeto
Deogratiuos Tukwasibwe
Shafic Makumbi
Emily Ninsiima
Mercy Tukamushaba
Rogers Ankunda
Ian Natuhurira
Miriam Kasozi
Baker Rubinga
Adeodata R. Kekitiinwa
Dickson Bbuye
Justine Nalubwama
Winnie Akobye
Authors: Cecilia L. Moore
Anna Turkova
Hilda Mujuru
Adeodata Kekitiinwa
Abbas Lugemwa
Cissy M. Kityo
Linda N. Barlow-Mosha
Tim R. Cressey
Avy Violari
Ebrahim Variava
Mark F. Cotton
Moherndran Archary
Alexandra Compagnucci
Thanyawee Puthanakit
Osee Behuhuma
Yacine Saϊdi
James Hakim
Pauline Amuge
Lorna Atwine
Victor Musiime
David M. Burger
Clare Shakeshaft
Carlo Giaquinto
Pablo Rojo
Diana M. Gibb
Deborah Ford
Shabinah Ali
Abdel Babiker
Chiara Borg
Anne Marie Borges Da Silva
Joanna Calvert
Joshua Gasa
Nasir Jamil
Sarah Lensen
Emma Little
Fatima Mohamed
Samuel Montero
Cecilia L. Moore
Rachel Oguntimehin
Anna Parker
Reena Patel
Tasmin Phillips
Tatiana Sarfati
Karen Scott
Moira Spyer
Margaret Thomason
Rebecca Turner
Nadine Van Looy
Ellen White
Kaya Widuch
Helen Wilkes
Ben Wynne
Tiziana Grossele
Daniel Gomez-Pena
Davide Bilardi
Giulio Vecchia
Yacine Saidi
Yoann Riault
Alexandra Coelho
Laura Picault
Christelle Kouakam
Suwalai Chalermpantmetagul
Dujrudee Chinwong
Gonzague Jourdain
Rukchanok Peongjakta
Pra ornsuda Sukrakanchana
Wasna Sirirungsi
Janet Seeley
Sarah Bernays
Magda Conway
Nigel Klein
Eleni Nastouli
Anita De Rossi
Maria Angeles Munoz Fernandez
David Burger
Pauline Bollen
Angela Colbers
Hylke Waalewijn
Elizabeth Kaudha
Annet Nanduudu
Emmanuel Mujyambere
Paul Ocitti Labeja
Charity Nankunda
Juliet Ategeka
Peter Erim
Collin Makanga
Esther Nambi
Edridah Keminyeto
Deogratiuos Tukwasibwe
Shafic Makumbi
Emily Ninsiima
Mercy Tukamushaba
Rogers Ankunda
Ian Natuhurira
Miriam Kasozi
Baker Rubinga
Adeodata R. Kekitiinwa
Dickson Bbuye
Justine Nalubwama
Winnie Akobye
Keywords: Medicine
Issue Date: 1-Dec-2021
Abstract: Background: Dolutegravir (DTG)-based antiretroviral therapy (ART) is highly effective and well-tolerated in adults and is rapidly being adopted globally. We describe the design of the ODYSSEY trial which evaluates the efficacy and safety of DTG-based ART compared with standard-of-care in children and adolescents. The ODYSSEY trial includes nested pharmacokinetic (PK) sub-studies which evaluated pragmatic World Health Organization (WHO) weight-band-based DTG dosing and opened recruitment to children < 14 kg while dosing was in development. Methods: ODYSSEY (Once-daily DTG based ART in Young people vS. Standard thErapY) is an open-label, randomised, non-inferiority, basket trial comparing the efficacy and safety of DTG + 2 nucleos(t) ides (NRTIs) versus standard-of-care (SOC) in HIV-infected children < 18 years starting first-line ART (ODYSSEY A) or switching to second-line ART (ODYSSEY B). The primary endpoint is clinical or virological failure by 96 weeks. Results: Between September 2016 and June 2018, 707 children weighing ≥14 kg were enrolled; including 311 ART-naïve children and 396 children starting second-line. 47% of children were enrolled in Uganda, 21% Zimbabwe, 20% South Africa, 9% Thailand, 4% Europe. 362 (51%) participants were male; median age [range] at enrolment was 12.2 years [2.9–18.0]. 82 (12%) children weighed 14 to < 20 kg, 135 (19%) 20 to < 25 kg, 206 (29%) 25 to < 35 kg, 284 (40%) ≥35 kg. 128 (18%) had WHO stage 3 and 60 (8%) WHO stage 4 disease. Challenges encountered include: (i) running the trial across high- to low-income countries with differing frequencies of standard-of-care viral load monitoring; (ii) evaluating pragmatic DTG dosing in PK sub-studies alongside FDA- and EMA-approved dosing and subsequently transitioning participants to new recommended doses; (iii) delays in dosing information for children weighing 3 to < 14 kg and rapid recruitment of ART-naïve older/heavier children, which led to capping recruitment of participants weighing ≥35 kg in ODYSSEY A and extending recruitment (above 700) to allow for ≥60 additional children weighing between 3 to < 14 kg with associated PK; (iv) a safety alert associated with DTG use during pregnancy, which required a review of the safety plan for adolescent girls. Conclusions: By employing a basket design, to include ART-naïve and -experienced children, and nested PK sub-studies, the ODYSSEY trial efficiently evaluates multiple scientific questions regarding dosing and effectiveness of DTG-based ART in children. Trial registration: NCT, NCT02259127, registered 7th October 2014; EUDRACT, 2014–002632-14, registered 18th June 2014 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002632-14/ES); ISRCTN, ISRCTN91737921, registered 4th October 2014.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85100093150&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/76954
ISSN: 14712334
Appears in Collections:CMUL: Journal Articles

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