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COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial

OBJECTIVES: The main goal of the COVIDENZA trial is to evaluate if inhibition of testosterone signalling by enzalutamide can improve the outcome of patients hospitalised for COVID-19. The hypothesis is based on the observation that the majority of patients in need of intensive care are male, and the...

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Autores principales: Welén, Karin, Överby, Anna K, Ahlm, Clas, Freyhult, Eva, Robinsson, David, Henningsson, Anna Jonsson, Stranne, Johan, Bremell, Daniel, Angelin, Martin, Lindquist, Elisabeth, Buckland, Robert, Carlsson, Camilla Thellenberg, Pauksens, Karlis, Bill-Axelsson, Anna, Akre, Olof, Ryden, Cecilia, Wagenius, Magnus, Bjartell, Anders, Nilsson, Anna C., Styrke, Johan, Repo, Johanna, Balkhed, Åse Östholm, Niward, Katarina, Gisslén, Magnus, Josefsson, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961321/
https://www.ncbi.nlm.nih.gov/pubmed/33726804
http://dx.doi.org/10.1186/s13063-021-05137-4
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author Welén, Karin
Överby, Anna K
Ahlm, Clas
Freyhult, Eva
Robinsson, David
Henningsson, Anna Jonsson
Stranne, Johan
Bremell, Daniel
Angelin, Martin
Lindquist, Elisabeth
Buckland, Robert
Carlsson, Camilla Thellenberg
Pauksens, Karlis
Bill-Axelsson, Anna
Akre, Olof
Ryden, Cecilia
Wagenius, Magnus
Bjartell, Anders
Nilsson, Anna C.
Styrke, Johan
Repo, Johanna
Balkhed, Åse Östholm
Niward, Katarina
Gisslén, Magnus
Josefsson, Andreas
author_facet Welén, Karin
Överby, Anna K
Ahlm, Clas
Freyhult, Eva
Robinsson, David
Henningsson, Anna Jonsson
Stranne, Johan
Bremell, Daniel
Angelin, Martin
Lindquist, Elisabeth
Buckland, Robert
Carlsson, Camilla Thellenberg
Pauksens, Karlis
Bill-Axelsson, Anna
Akre, Olof
Ryden, Cecilia
Wagenius, Magnus
Bjartell, Anders
Nilsson, Anna C.
Styrke, Johan
Repo, Johanna
Balkhed, Åse Östholm
Niward, Katarina
Gisslén, Magnus
Josefsson, Andreas
author_sort Welén, Karin
collection PubMed
description OBJECTIVES: The main goal of the COVIDENZA trial is to evaluate if inhibition of testosterone signalling by enzalutamide can improve the outcome of patients hospitalised for COVID-19. The hypothesis is based on the observation that the majority of patients in need of intensive care are male, and the connection between androgen receptor signalling and expression of TMPRSS2, an enzyme important for SARS-CoV-2 host cell internalization. TRIAL DESIGN: Hospitalised COVID-19 patients will be randomised (2:1) to enzalutamide plus standard of care vs. standard of care designed to identify superiority. PARTICIPANTS: Included participants, men or women above 50 years of age, must be hospitalised for PCR confirmed COVID-19 symptoms and not in need of immediate mechanical ventilation. Major exclusion criteria are breast-feeding or pregnant women, hormonal treatment for prostate or breast cancer, treatment with immunosuppressive drugs, current symptomatic unstable cardiovascular disease (see Additional file 1 for further details). The trial is registered at Umeå University Hospital, Region Västerbotten, Sweden and 8 hospitals are approved for inclusion in Sweden. INTERVENTION AND COMPARATOR: Patients randomised to the treatment arm will be treated orally with 160 mg (4x40 mg) enzalutamide (Xtandi®) daily, for five consecutive days. The study is not placebo controlled. The comparator is standard of care treatment for patients hospitalised with COVID-19. MAIN OUTCOMES: The primary endpoints of the study are (time to) need of mechanical ventilation or discharge from hospital as assessed by a clinical 7-point ordinal scale (up to 30 days after inclusion). RANDOMISATION: Randomisation was stratified by center and sex. Each strata was randomized separately with block size six with a 2:1 allocation ratio (enzalutamide + “standard of care”: “standard of care”). The randomisation list, with consecutive subject numbers, was generated by an independent statistician using the PROC PLAN procedure of SAS version 9.4 software (SAS Institute, Inc, Cary, North Carolina) BLINDING (MASKING): This is an open-label trial. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The trial is designed to have three phases. The first, an exploration phase of 45 participants (30 treatment and 15 control) will focus on safety and includes a more extensive laboratory assessment as well as more frequent safety evaluation. The second prolongation phase, includes the first 100 participants followed by an interim analysis to define the power of the study. The third phase is the continuation of the study up to maximum 600 participants included in total. TRIAL STATUS: The current protocol version is COVIDENZA v2.0 as of September 10, 2020. Recruitment started July 29, 2020 and is presently in safety pause after the first exploration phase. Recruitment is anticipated to be complete by 31 December 2021. TRIAL REGISTRATION: Eudract number 2020-002027-10 ClinicalTrials.gov Identifier: NCT04475601, registered June 8, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-021-05137-4.
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spelling pubmed-79613212021-03-16 COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial Welén, Karin Överby, Anna K Ahlm, Clas Freyhult, Eva Robinsson, David Henningsson, Anna Jonsson Stranne, Johan Bremell, Daniel Angelin, Martin Lindquist, Elisabeth Buckland, Robert Carlsson, Camilla Thellenberg Pauksens, Karlis Bill-Axelsson, Anna Akre, Olof Ryden, Cecilia Wagenius, Magnus Bjartell, Anders Nilsson, Anna C. Styrke, Johan Repo, Johanna Balkhed, Åse Östholm Niward, Katarina Gisslén, Magnus Josefsson, Andreas Trials Letter OBJECTIVES: The main goal of the COVIDENZA trial is to evaluate if inhibition of testosterone signalling by enzalutamide can improve the outcome of patients hospitalised for COVID-19. The hypothesis is based on the observation that the majority of patients in need of intensive care are male, and the connection between androgen receptor signalling and expression of TMPRSS2, an enzyme important for SARS-CoV-2 host cell internalization. TRIAL DESIGN: Hospitalised COVID-19 patients will be randomised (2:1) to enzalutamide plus standard of care vs. standard of care designed to identify superiority. PARTICIPANTS: Included participants, men or women above 50 years of age, must be hospitalised for PCR confirmed COVID-19 symptoms and not in need of immediate mechanical ventilation. Major exclusion criteria are breast-feeding or pregnant women, hormonal treatment for prostate or breast cancer, treatment with immunosuppressive drugs, current symptomatic unstable cardiovascular disease (see Additional file 1 for further details). The trial is registered at Umeå University Hospital, Region Västerbotten, Sweden and 8 hospitals are approved for inclusion in Sweden. INTERVENTION AND COMPARATOR: Patients randomised to the treatment arm will be treated orally with 160 mg (4x40 mg) enzalutamide (Xtandi®) daily, for five consecutive days. The study is not placebo controlled. The comparator is standard of care treatment for patients hospitalised with COVID-19. MAIN OUTCOMES: The primary endpoints of the study are (time to) need of mechanical ventilation or discharge from hospital as assessed by a clinical 7-point ordinal scale (up to 30 days after inclusion). RANDOMISATION: Randomisation was stratified by center and sex. Each strata was randomized separately with block size six with a 2:1 allocation ratio (enzalutamide + “standard of care”: “standard of care”). The randomisation list, with consecutive subject numbers, was generated by an independent statistician using the PROC PLAN procedure of SAS version 9.4 software (SAS Institute, Inc, Cary, North Carolina) BLINDING (MASKING): This is an open-label trial. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The trial is designed to have three phases. The first, an exploration phase of 45 participants (30 treatment and 15 control) will focus on safety and includes a more extensive laboratory assessment as well as more frequent safety evaluation. The second prolongation phase, includes the first 100 participants followed by an interim analysis to define the power of the study. The third phase is the continuation of the study up to maximum 600 participants included in total. TRIAL STATUS: The current protocol version is COVIDENZA v2.0 as of September 10, 2020. Recruitment started July 29, 2020 and is presently in safety pause after the first exploration phase. Recruitment is anticipated to be complete by 31 December 2021. TRIAL REGISTRATION: Eudract number 2020-002027-10 ClinicalTrials.gov Identifier: NCT04475601, registered June 8, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-021-05137-4. BioMed Central 2021-03-16 /pmc/articles/PMC7961321/ /pubmed/33726804 http://dx.doi.org/10.1186/s13063-021-05137-4 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.
spellingShingle Letter
Welén, Karin
Överby, Anna K
Ahlm, Clas
Freyhult, Eva
Robinsson, David
Henningsson, Anna Jonsson
Stranne, Johan
Bremell, Daniel
Angelin, Martin
Lindquist, Elisabeth
Buckland, Robert
Carlsson, Camilla Thellenberg
Pauksens, Karlis
Bill-Axelsson, Anna
Akre, Olof
Ryden, Cecilia
Wagenius, Magnus
Bjartell, Anders
Nilsson, Anna C.
Styrke, Johan
Repo, Johanna
Balkhed, Åse Östholm
Niward, Katarina
Gisslén, Magnus
Josefsson, Andreas
COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial
title COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial
title_full COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial
title_fullStr COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial
title_full_unstemmed COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial
title_short COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial
title_sort covidenza - a prospective, multicenter, randomized phase ii clinical trial of enzalutamide treatment to decrease the morbidity in patients with corona virus disease 2019 (covid-19): a structured summary of a study protocol for a randomised controlled trial
topic Letter
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961321/
https://www.ncbi.nlm.nih.gov/pubmed/33726804
http://dx.doi.org/10.1186/s13063-021-05137-4
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