BMJ Open (Nov 2019)

Effect of high-dose vitamin D3 on 28-day mortality in adult critically ill patients with severe vitamin D deficiency: a study protocol of a multicentre, placebo-controlled double-blind phase III RCT (the VITDALIZE study)

  • Dhruv Parekh,
  • David Thickett,
  • Gemma Slinn,
  • Peter Brocklehurst,
  • Danny Mcauley,
  • Maria Wittmann,
  • Teresa Melody,
  • Jaimin Patel,
  • Gavin Perkins,
  • Markus Kredel,
  • Peter Kranke,
  • Christian Stoppe,
  • Lars Hummitzsch,
  • Norbert Weiler,
  • Karin Amrein,
  • Sabine Westphal,
  • Jean-Charles Preiser,
  • Andrea Berghold,
  • Regina Riedl,
  • Philipp Eller,
  • Peter Schellongowski,
  • Patrick Meybohm,
  • Corinna Marschalek,
  • Rene Schmutz,
  • Martin Clodi,
  • Michael Resl,
  • Mario Krasser,
  • Matthias Michlmayr,
  • Johann Reisinger,
  • Alexandra Schiller,
  • Nicolas Dominik Verheyen,
  • Dirk von Lewinski,
  • Marlene Sandra Deininger,
  • Andreas Muench,
  • Holger Simonis,
  • Paul Zajic,
  • Ines Lindenau,
  • Alexander Holl,
  • Alexander Pichler,
  • Tadeja Urbanic Purkart,
  • Katharina Ritsch,
  • Simon Schmidt,
  • Romuald Bellmann,
  • Anna Brandtner,
  • Adelheid Ditlbacher,
  • Julia Hasslacher,
  • Michael Joannidis,
  • Andreas Peer,
  • Klemens Zotter,
  • Christoph Martin Biedermann,
  • Andreas Valentin,
  • Franz Wimmer,
  • Susanne Demschar,
  • Markus Koestenberger,
  • Rudolf Likar,
  • Stefan Neuwersch,
  • Michael Pogatschnigg,
  • Brigitte Trummer,
  • Martin Duenser,
  • Jens Meier,
  • Johann Kainz,
  • Romana Sommer,
  • Otmar Schindler,
  • Alexander Lehr,
  • Guenter Mesaric,
  • Yasmin Tinawi,
  • Norbert Watzinger,
  • Randolf Hammerl,
  • Peter Krippl,
  • Stefan Langner,
  • Martin Lux,
  • Matthias Unteregger,
  • Gerwig Fruehauf,
  • Barbara Gruber,
  • Bertram Harzl,
  • Viktor Wutzl,
  • Juergen Berghofer,
  • Nadine Fuch,
  • Gilbert Hainzl,
  • Isolde Pessentheiner,
  • Michael Zink,
  • Petra Hoernler,
  • Ernst Trampitsch,
  • Jakob Muehlbacher,
  • Philipp Riss,
  • Roman Ullrich,
  • Martin Bernardi,
  • Michael Hiesmayr,
  • Katharina Kovac,
  • Cecilia Veraar,
  • Bernhard Zapletal,
  • Elisabeth Lobmeyr,
  • Esther Tiller,
  • Georg Hinterholzer,
  • Daniel Mydza,
  • Sabine Schmaldienst,
  • Maxime van Cutsem,
  • Marianne Blockmans,
  • Alain D’hondt,
  • Vincent Fraipont,
  • Sophie Jacquet,
  • Caroline Abbenhuijs,
  • Katarina Helenarova,
  • Romain Courcelle,
  • Dominique Durand,
  • Amedee Ego,
  • Amina Khaldi,
  • Itesa Nancy Matumikina,
  • Kai Zacharowski,
  • Simone Lindau,
  • Philipp Helmer,
  • Gunnar Elke,
  • Guenther Zick,
  • Tobias Becher,
  • Dirk Schaedler,
  • Matthias Kott,
  • Barbara Vogt,
  • Ingmar Lautenschlaeger,
  • Georg Fuernau,
  • Christian Putensen,
  • Stefan Ehrentraut,
  • Barbara Kapfer,
  • Thomas Felbinger,
  • Ines Kaufmann,
  • Bjoern Andrew Rempiss,
  • Claudia Spiess,
  • Stefan Schaller,
  • Tobias Schlesinger,
  • Magdalena Sitter,
  • Jan Stumpner,
  • Nico Schlegel,
  • Christoph Schimmer,
  • Ekkehard Kunze,
  • Thomas Kerz,
  • Dominik Wesp,
  • Axel Neule,
  • Florian Ringel,
  • Mario Maggiorini,
  • Stephan Jakob,
  • Joerg Schefold,
  • Rebekah Wale,
  • Marlies Ostermann,
  • Matthew Morgan,
  • Mervyn Singer,
  • Matthew Rowland

DOI
https://doi.org/10.1136/bmjopen-2019-031083
Journal volume & issue
Vol. 9, no. 11

Abstract

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Introduction Observational studies have demonstrated an association between vitamin D deficiency and increased risk of morbidity and mortality in critically ill patients. Cohort studies and pilot trials have suggested promising beneficial effects of vitamin D replacement in the critical ill, at least in patients with severe vitamin D deficiency. As vitamin D is a simple, low-cost and safe intervention, it has potential to improve survival in critically ill patients.Methods and analysis In this randomised, placebo-controlled, double-blind, multicentre, international trial, 2400 adult patients with severe vitamin D deficiency (25-hydroxyvitamin D≤12 ng/mL) will be randomised in a 1:1 ratio by www.randomizer.at to receive a loading dose of 540 000 IU cholecalciferol within 72 hours after intensive care unit (ICU) admission, followed by 4000 IU daily for 90 days or placebo. Hypercalcaemia may occur as a side effect, but is monitored by regular checks of the calcium level. The primary outcome is all-cause mortality at 28 days after randomisation. Secondary outcomes are: ICU, hospital, 90-day and 1-year mortality; hospital and ICU length of stay, change in organ dysfunction on day 5 as measured by Sequential Organ Function Assessment (SOFA) score, number of organ failures; hospital and ICU readmission until day 90; discharge destination, self-reported infections requiring antibiotics until day 90 and health-related quality of life. Recruitment status is ongoing.Ethics and dissemination National ethical approval was obtained by the Ethics Committee of the University of Graz for Austria, Erasme University Brussels (Belgium) and University Hospital Frankfurt (Germany), and will further be gained according to individual national processes. On completion, results will be published in a peer-reviewed scientific journal. The study findings will be presented at national and international meetings with abstracts online.Trial registration NCT03188796, EudraCT-No: 2016-002460-13.