Clinical trial NCT03745664: Corticosteroids and Myocardial Injury in CAP (COLOSSEUM TRIAL)
Official title: Effect of Corticosteroids On MyocardiaL Injury Among Patients Hospitalized for Community-AcquirEd PneUMonia - COLOSSEUM TRIAL
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Community-acquired Pneumonia
Keywords: corticosteroids
Lead sponsor: University of Roma La Sapienza
Sponsor class: OTHER
Collaborators: name: Azienda Policlinico Umberto I
First posted: 2018-11-19
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 3, multicenter, double-blind, placebo-controlled, randomized, intervention trial
Primary purpose: TREATMENT

Brief summary: Community-acquired pneumonia (CAP) is often complicated by elevation of cardiac troponin, a marker of myocardial injury, that can be isolated or associated to myocardial infarction (MI). A retrospective study showed that corticosteroid treatment lowers incidence of MI during the hospital-stay.

The aim of this clinical trial is to examine whether in-hospital treatment with iv methylprednisolone (20 mg b.i.d) may reduce myocardial injury, as assessed by serum high-sensitivity cardiac T Troponin) and eventually cardiovascular events during a short- and long-term follow-up in patients hospitalized CAP.

Detailed description: Background. Community-acquired pneumonia (CAP) is often complicated by elevation of cardiac troponin, a marker of myocardial injury, that can be isolated or associated to myocardial infarction (MI). A retrospective study showed that corticosteroid treatment lowers incidence of MI during the hospital-stay. No data exist so far on the effect of corticosteroids on myocardial injury in CAP patients.

Study design. Double-blind randomized placebo-controlled trial. One hundred twenty-two eligible patients will be randomized to a week treatment with iv methylprednisolone (20 mg b.i.d) or placebo from hospital admission. Serum hs-cTnT will be measured at admission and every day until up 3 days from admission. ECG will be monitored every day until discharge. After dismission, all patients will be followed-up 2 years.

Aims of the study. Primary objective of the study is to evaluate if methylprednisolone is able to reduce myocardial injury, as assessed by serum high-sensitivity cardiac T Troponin (hs-cTnT), in a cohort of patients hospitalized for CAP.

Secondary aims are to evaluate the potential effect of methylprednisolone on cardiovascular events during hospitalization, at 30 day from hospital admission and during 2 years' follow-up. The trial will also examine whether the potential protective effects of methylprednisolone might be due to platelet activation down-regulation.

Eligibility criteria: Inclusion Criteria:

Hospitalization for community-acquired pneumonia

Exclusion Criteria:

1. Use of corticosteroids in the previous 30 days
2. Health Care-Associated Pneumonia
3. Reported severe immunosuppression (human immunodeficiency virus infection, immunosuppressive conditions or medications)
4. Preexisting medical condition with a life expectancy of less than 3 months
5. Uncontrolled diabetes mellitus
6. Gastritis with or without major gastrointestinal bleeding within 3 months
7. Any condition requiring acute treatment with glucocorticoids

Primary outcomes:
measure: High sensitivity cardiac T troponin (myocardial injury biomarker)
timeFrame: 7 days
Secondary outcomes:
measure: Serum TxB2 (biomarker of platelet activation)
timeFrame: 7 days
measure: sP-selectin (biomarker of platelet activation).
timeFrame: 7 days
measure: sCD40L (biomarker of platelet activation).
timeFrame: 7 days
measure: High-sensitivity C-Reactive Protein
timeFrame: 7 days
measure: Serum sNOX2-dp (biomarker of oxidative stress)
timeFrame: 7 days
measure: Serum F2-isoprostanes (biomarker of oxidative stress)
timeFrame: 7 days
measure: Urinary F2-isoprostanes (biomarker of oxidative stress)
timeFrame: 7 days
measure: Cardiovascular events during hospitalization.
timeFrame: 7 days
measure: Major adverse cardiac and cerebrovascular events (MACCE) at 30 days.
timeFrame: 30 days
measure: Major adverse cardiac and cerebrovascular events (MACCE) during a a long-term follow-up.
timeFrame: 2 years
measure: Short-term mortality
timeFrame: 30 days
measure: Long-term mortality
timeFrame: 2 years
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Sapienza University of Rome
Study officials:
affiliation: University of Roma La Sapienza
name: Francesco Violi, MD
role: STUDY_CHAIR
affiliation: University of Roma La Sapienza
name: Roberto Cangemi
role: STUDY_DIRECTOR
References:
citation: Cangemi R, Casciaro M, Rossi E, Calvieri C, Bucci T, Calabrese CM, Taliani G, Falcone M, Palange P, Bertazzoni G, Farcomeni A, Grieco S, Pignatelli P, Violi F; SIXTUS Study Group; SIXTUS Study Group. Platelet activation is associated with myocardial infarction in patients with pneumonia. J Am Coll Cardiol. 2014 Nov 4;64(18):1917-25. doi: 10.1016/j.jacc.2014.07.985. Epub 2014 Oct 27.
citation: Cangemi R, Falcone M, Taliani G, Calvieri C, Tiseo G, Romiti GF, Bertazzoni G, Farcomeni A, Violi F; SIXTUS Study Group. Corticosteroid Use and Incident Myocardial Infarction in Adults Hospitalized for Community-acquired Pneumonia. Ann Am Thorac Soc. 2019 Jan;16(1):91-98. doi: 10.1513/AnnalsATS.201806-419OC.
citation: Cangemi R, Carnevale R, Nocella C, Calvieri C, Cammisotto V, Novo M, Castellani V, D'Amico A, Zerbinati C, Stefanini L, Violi F; SIXTUS Study Group. Glucocorticoids impair platelet thromboxane biosynthesis in community-acquired pneumonia. Pharmacol Res. 2018 May;131:66-74. doi: 10.1016/j.phrs.2018.03.014. Epub 2018 Mar 22.
citation: Liverani E, Banerjee S, Roberts W, Naseem KM, Perretti M. Prednisolone exerts exquisite inhibitory properties on platelet functions. Biochem Pharmacol. 2012 May 15;83(10):1364-73. doi: 10.1016/j.bcp.2012.02.006. Epub 2012 Feb 16.