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Adjunctive treatment with oral dexamethasone in non-ICU patients hospitalised with community-acquired pneumonia: A randomised clinical trial

Esther Wittermans, Stefan MT Vestjens, Simone MC Spoorenberg, Willem L Blok, Jan C Grutters, Rob Janssen, Ger T Rijkers, Frank WJM Smeenk, Paul Voorn, Ewoudt MW van de Garde, Willem Jan W Bos, The Santeon-CAP study group
European Respiratory Journal 2021; DOI: 10.1183/13993003.02535-2020
Esther Wittermans
1Department of Internal Medicine, St. Antonius Hospital, Nieuwegein, the Netherlands
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  • For correspondence: e.wittermans@antoniusziekenhuis.nl
Stefan MT Vestjens
1Department of Internal Medicine, St. Antonius Hospital, Nieuwegein, the Netherlands
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Simone MC Spoorenberg
1Department of Internal Medicine, St. Antonius Hospital, Nieuwegein, the Netherlands
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Willem L Blok
2Department of Internal Medicine, OLVG, Amsterdam, the Netherlands
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Jan C Grutters
3Department of Pulmonology, St. Antonius Hospital, Nieuwegein, the Netherlands
4Division of Heart and Lungs, University Medical Centre Utrecht, Utrecht, the Netherlands
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Rob Janssen
5Department of Pulmonology, Canisius Wilhelmina Hospital, Nijmegen, the Netherlands
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  • ORCID record for Rob Janssen
Ger T Rijkers
6Department of Science University College Roosevelt, Middelburg, the Netherlands
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Frank WJM Smeenk
7Department of Pulmonology, Catharina Hospital, Eindhoven, the Netherlands
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Paul Voorn
8Department of Medical Microbiology and Immunology, St. Antonius Hospital, Nieuwegein, the Netherlands
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Ewoudt MW van de Garde
9Department of Clinical Pharmacology, St. Antonius Hospital, the Netherlands
10Division of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Utrecht University, Utrecht, the Netherlands
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Willem Jan W Bos
1Department of Internal Medicine, St. Antonius Hospital, Nieuwegein, the Netherlands
11Department of Internal Medicine – division Nephrology, Leiden University Medical Centre, Leiden, the Netherlands
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Abstract

Background Adjunctive intravenous corticosteroid treatment has shown to reduce length of stay (LOS) in adults hospitalised with community-acquired pneumonia (CAP). We aimed to assess the effect of oral dexamethasone on LOS and whether this effect is disease severity dependent.

Methods In this multicentre, stratified randomised, double-blind, placebo-controlled trial, immunocompetent adults with CAP were randomly assigned (1:1 ratio) to receive oral dexamethasone (6 mg once daily) or placebo for 4 days in four teaching hospitals in the Netherlands. Randomisation (blocks of four) was stratified by CAP severity (pneumonia severity index class I–III and IV-V). The primary outcome was LOS. This study is registered with ClinicalTrials.gov (NCT01743755).

Results Between December 2012 and November 2018, 401 patients were randomised to receive dexamethasone (n=203) or placebo (n=198). Median LOS was shorter in the dexamethasone group (4.5 days (95% CI 4.0–5.0)) than in the placebo group (5.0 days (95% CI 4.6–5.4); p=0.033). Within both CAP severity subgroups, differences in LOS between treatment groups were not statistically significant. Secondary ICU admission rate was lower in the dexamethasone arm (5 (3%) versus 14 (7%), p=0.030), 30-day mortality did not differ between groups. In the dexamethasone group rate of hospital readmission tended to be higher (20 (10%) versus 9 (5%); p=0.051) and hyperglycaemia (14 (7%) versus 1 (1%); p=0.001) was more prevalent.

Conclusion Oral dexamethasone reduced LOS and ICU admission rate in adults hospitalised with CAP. It remains unclear for which patients the risk-benefit ratio is optimal.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflict of interest: Dr. Wittermans has nothing to disclose.

Conflict of interest: Dr. Vestjesn has nothing to disclose.

Conflict of interest: Dr. Spoorenberg has nothing to disclose.

Conflict of interest: Dr. Blok has nothing to disclose.

Conflict of interest: Dr. Grutters has nothing to disclose.

Conflict of interest: Dr. Janssen has nothing to disclose.

Conflict of interest: Dr. Rijkers has nothing to disclose.

Conflict of interest: Dr. Smeenk has nothing to disclose.

Conflict of interest: Dr. Voorn has nothing to disclose.

Conflict of interest: Dr. van de Garde has nothing to disclose.

Conflict of interest: Dr. Bos reports grants from Zilveren Kruis Insurance, outside the submitted work;.

  • Received July 3, 2020.
  • Accepted December 27, 2020.
  • ©The authors 2021. For reproduction rights and permissions contact permissions{at}ersnet.org
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Adjunctive treatment with oral dexamethasone in non-ICU patients hospitalised with community-acquired pneumonia: A randomised clinical trial
Esther Wittermans, Stefan MT Vestjens, Simone MC Spoorenberg, Willem L Blok, Jan C Grutters, Rob Janssen, Ger T Rijkers, Frank WJM Smeenk, Paul Voorn, Ewoudt MW van de Garde, Willem Jan W Bos, The Santeon-CAP study group
European Respiratory Journal Jan 2021, 2002535; DOI: 10.1183/13993003.02535-2020

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Adjunctive treatment with oral dexamethasone in non-ICU patients hospitalised with community-acquired pneumonia: A randomised clinical trial
Esther Wittermans, Stefan MT Vestjens, Simone MC Spoorenberg, Willem L Blok, Jan C Grutters, Rob Janssen, Ger T Rijkers, Frank WJM Smeenk, Paul Voorn, Ewoudt MW van de Garde, Willem Jan W Bos, The Santeon-CAP study group
European Respiratory Journal Jan 2021, 2002535; DOI: 10.1183/13993003.02535-2020
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