Corticosteroid Treatment for Community-Acquired Pneumonia - The STEP Trial

NCT00973154 | Completed Phase 3 DMC

• 1 other identifier: STEP
• Study Type: interventional
• Target: 800
• Locations: 1 country
• Sites: 7

Brief Summary

Background: An intact hypothalami-pituitary-adrenal (HPA) axis with an effective intracellular anti-inflammatory activity of glucocorticoids is indispensable for host survival during stress upon exposure to an infectious agent. Community-acquired pneumonia (CAP) is characterized by significant mortality and increased circulating inflammatory cytokines. Despite adequate antimicrobial therapy mortality rates for CAP have not changed over several decades. The use of corticosteroids in patients with CAP is inconclusive. Study aim: To compare a 7 days treatment with prednisone and placebo in patients with community-acquired pneumonia with respect to time to clinical stability. Study hypothesis: The investigators hypothesize that use of corticosteroids will lead to a 25% relative risk reduction for death and clinical instability. Study type: randomized double blind intervention study Patients: 800 patients with community-acquired pneumonia

Conditions

Community-acquired Pneumonia

Keywords

Pneumonia; Corticosteroids; clinical stability

Outcome Measures

Primary Outcomes (1)

• Time to clinical stability

  30 days

Secondary Outcomes (1)

• Side effects of corticosteroids, mortality, recurrence

  30 days

Study Arms (2)

Prednisone

ACTIVE COMPARATOR

Drug

Drug: Prednisone

Placebo

PLACEBO COMPARATOR

Drug: Prednisone

Interventions

Prednisone DRUG

50mg per day of prednisone orally for 7 days versus placebo

Placebo; Prednisone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients 18 years of age or older admitted for hospitalization from the community or a nursing home with CAP.
• CAP will be defined by a new infiltrate on chest radiograph and the presence of one or several of the following acute respiratory signs or symptoms:
• cough
• sputum production
• dyspnea
• core body temperature \>38.0° C
• auscultatory findings of abnormal breath sounds and rales
• leukocyte count \>10 or \<4 x 109 cells L-1 (1)

You may not qualify if:

• Patients or family members unable to give written informed consent, e.g. with severe dementia.
• Patients with active intravenous drug use.
• Severe immunosuppression (e.g. patients infected with human immunodeficiency virus infection and a CD4 count below 350 x 109/L, patients on immunosuppressive therapy after solid organ transplantation and neutropenic patients with neutrophil count \< 500 x 109/L and patients under chemotherapy with neutrophils 500-1000 x 109/L with an expected decrease to values \< 500 x 109/L); patients with cystic fibrosis as well as patients with active tuberculosis.
• Patients with acute burn injury
• Patients with acute gastrointestinal bleeding within 3 months of the current hospitalization
• Patients with an acute concomitant condition requiring more than 0.5mg/kg/d prednisone equivalent
• Pregnancy or breast feeding
• Patients with known adrenal insufficiency

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Kantonsspital Aarau: collaborator
• Kantonsspital Liestal: collaborator

Study Sites (7)

Medizinische Klinik, Kantonsspital Liestal

Liestal, Basel-Landschaft, 4410, Switzerland

Location

Medicine Interne, Hôpital du Jura, site de Delémont

Delémont, Canton of Jura, 2800, Switzerland

Location

Kantonsspital Aarau

Aarau, Switzerland

Location

University Hospital Basel

Basel, 4031, Switzerland

Location

Inselspital

Bern, Switzerland

Location

Bruderholzspital

Bruderholz, Switzerland

Location

Bürgerspital

Solothurn, Switzerland

Location

Related Publications (10)

• Blum CA, Roethlisberger EA, Cesana-Nigro N, Winzeler B, Rodondi N, Blum MR, Briel M, Mueller B, Christ-Crain M, Schuetz P. Adjunct prednisone in community-acquired pneumonia: 180-day outcome of a multicentre, double-blind, randomized, placebo-controlled trial. BMC Pulm Med. 2023 Dec 11;23(1):500. doi: 10.1186/s12890-023-02794-w.

  PMID: 38082273 DERIVED

• Borisov AN, Blum CA, Christ-Crain M, Ebrahimi F. No obesity paradox in patients with community-acquired pneumonia - secondary analysis of a randomized controlled trial. Nutr Diabetes. 2022 Mar 23;12(1):12. doi: 10.1038/s41387-022-00190-7.

  PMID: 35322019 DERIVED

• Sailer CO, Refardt J, Blum CA, Schnyder I, Molina-Tijeras JA, Fenske W, Christ-Crain M. Validity of different copeptin assays in the differential diagnosis of the polyuria-polydipsia syndrome. Sci Rep. 2021 May 12;11(1):10104. doi: 10.1038/s41598-021-89505-9.

  PMID: 33980941 DERIVED

• Potasso L, Sailer CO, Blum CA, Cesana-Nigro N, Schuetz P, Mueller B, Christ-Crain M. Mild to moderate hyponatremia at discharge is associated with increased risk of recurrence in patients with community-acquired pneumonia. Eur J Intern Med. 2020 May;75:44-49. doi: 10.1016/j.ejim.2019.12.009. Epub 2020 Jan 15.

  PMID: 31952985 DERIVED

• Popovic M, Cesana-Nigro N, Winzeler B, Thomann R, Schutz P, Muller B, Christ-Crain M, Blum CA. Estimation of treatment allocation in a randomised, double-blinded, placebo-controlled trial. Swiss Med Wkly. 2019 Jul 24;149:w20114. doi: 10.4414/smw.2019.20114. eCollection 2019 Jul 15.

  PMID: 31340056 DERIVED

• Blum CA, Schuetz P, Nigro N, Winzeler B, Arici B, Refardt J, Urwyler SA, Rodondi N, Blum MR, Briel M, Mueller B, Christ-Crain M. Cosyntropin testing does not predict response to glucocorticoids in community-acquired pneumonia in a randomized controlled trial. Clin Endocrinol (Oxf). 2019 Sep;91(3):374-382. doi: 10.1111/cen.13907. Epub 2019 Jan 9.

  PMID: 30485501 DERIVED

• Popovic M, Blum CA, Nigro N, Mueller B, Schuetz P, Christ-Crain M. Benefit of adjunct corticosteroids for community-acquired pneumonia in diabetic patients. Diabetologia. 2016 Dec;59(12):2552-2560. doi: 10.1007/s00125-016-4091-4. Epub 2016 Sep 10.

  PMID: 27614658 DERIVED

• Wirz SA, Blum CA, Schuetz P, Albrich WC, Noppen C, Mueller B, Christ-Crain M, Tarr PE; STEP Study Group. Pathogen- and antibiotic-specific effects of prednisone in community-acquired pneumonia. Eur Respir J. 2016 Oct;48(4):1150-1159. doi: 10.1183/13993003.00474-2016. Epub 2016 Jul 28.

  PMID: 27471201 DERIVED

• Blum CA, Nigro N, Briel M, Schuetz P, Ullmer E, Suter-Widmer I, Winzeler B, Bingisser R, Elsaesser H, Drozdov D, Arici B, Urwyler SA, Refardt J, Tarr P, Wirz S, Thomann R, Baumgartner C, Duplain H, Burki D, Zimmerli W, Rodondi N, Mueller B, Christ-Crain M. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2015 Apr 18;385(9977):1511-8. doi: 10.1016/S0140-6736(14)62447-8. Epub 2015 Jan 19.

  PMID: 25608756 DERIVED

• Blum CA, Nigro N, Winzeler B, Suter-Widmer I, Schuetz P, Briel M, Bingisser R, Zimmerli W, Ullmer E, Elsaesser H, Tarr P, Wirz S, Thomann R, Hofmann E, Rodondi N, Duplain H, Burki D, Mueller B, Christ-Crain M. Corticosteroid treatment for community-acquired pneumonia--the STEP trial: study protocol for a randomized controlled trial. Trials. 2014 Jun 28;15:257. doi: 10.1186/1745-6215-15-257.

  PMID: 24974155 DERIVED

MeSH Terms

Conditions

Community-Acquired Pneumonia; Pneumonia

Interventions

Prednisone

Condition Hierarchy (Ancestors)

Community-Acquired Infections; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Mirjam Christ-Crain, MD

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med. Leitende Aerztin

Study Record Dates

• First Submitted: September 7, 2009
• First Posted: September 9, 2009
• Study Start: December 1, 2009
• Primary Completion: July 1, 2014
• Study Completion: December 1, 2014
• Last Updated: April 21, 2015

Record last verified: 2014-05

Locations

CH (7)