Corticosteroid Treatment for Community-Acquired Pneumonia - The STEP Trial

NCT ID: NCT00973154

Last Updated: 2015-04-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 800 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2014-12-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Prednisone

Drug

Group Type: ACTIVE_COMPARATOR

Prednisone

Intervention Type: DRUG

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

Placebo

Group Type: PLACEBO_COMPARATOR

Prednisone

Intervention Type: DRUG

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

Interventions

Prednisone

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients 18 years of age or older admitted for hospitalization from the community or a nursing home with CAP.

2. 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)

Exclusion Criteria

1. Patients or family members unable to give written informed consent, e.g. with severe dementia.

2. Patients with active intravenous drug use.

3. 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.

4. Patients with acute burn injury

5. Patients with acute gastrointestinal bleeding within 3 months of the current hospitalization

6. Patients with an acute concomitant condition requiring more than 0.5mg/kg/d prednisone equivalent

7. Pregnancy or breast feeding

8. Patients with known adrenal insufficiency

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kantonsspital Aarau

OTHER

Sponsor Role: collaborator

Kantonsspital Liestal

OTHER

Sponsor Role: collaborator

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Mirjam Christ-Crain

Prof. Dr. med. Leitende Aerztin

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mirjam Christ-Crain, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Basel, Switzerland

Locations

Medizinische Klinik, Kantonsspital Liestal

Liestal, Basel-Landschaft, Switzerland

Medicine Interne, Hôpital du Jura, site de Delémont

Delémont, Canton of Jura, Switzerland

Kantonsspital Aarau

Aarau, , Switzerland

University Hospital Basel

Basel, , Switzerland

Inselspital

Bern, , Switzerland

Bruderholzspital

Bruderholz, , Switzerland

Bürgerspital

Solothurn, , Switzerland

Countries

Switzerland

References

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.

Reference Type: DERIVED

PMID: 38082273 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35322019 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33980941 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31952985 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31340056 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30485501 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27614658 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27471201 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25608756 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24974155 (View on PubMed)

Other Identifiers

STEP

Identifier Type: -

Identifier Source: org_study_id