Corticosteroids and Myocardial Injury in CAP (COLOSSEUM TRIAL)

Community-acquired Pneumonia Clinical Trial

— COLOSSEUM  

Official title:

Effect of Corticosteroids On MyocardiaL Injury Among Patients Hospitalized for Community-AcquirEd PneUMonia - COLOSSEUM TRIAL

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03745664
• Other study ID #: COLOSSEUM trial - Rif 5133
• Status: Recruiting
• Phase: Phase 3
• Start date: January 10, 2021
• Est. completion date: September 1, 2024

Study information

• Verified date: September 2021
• Source: University of Roma La Sapienza
• Contact: Francesco Violi, MD
• Phone: 064461933
• Email: francesco.violi[@]uniroma1.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 122
• Est. completion date: September 1, 2024
• Est. primary completion date: May 16, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Community-acquired Pneumonia
• Pneumonia

Intervention

Drug:
• Methylprednisolone Sodium Succinate
During hospitalization, 40 mg of methylprednisolone (20 mg/ml) will be given intravenously twice a day (20 mg every 12 hours).
• Saline Solution for Injection
During hospitalization, 2 ml of Saline Solution for Injection will be given intravenously twice a day (2 ml every 12 hours).

Locations

Country	Name	City	State
Italy	Sapienza University of Rome	Rome

Sponsors (2)

Lead Sponsor	Collaborator
University of Roma La Sapienza	Azienda Policlinico Umberto I

Country where clinical trial is conducted

Italy, 

References & Publications (4)

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. Erratum in: Pharmacol Res. 2018 Sep;135:268. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	High sensitivity cardiac T troponin (myocardial injury biomarker)	Primary endpoint of the study will be a significant reduction of hs-cTnT increase. Hs-cTnT will be measured . Hs-cTnT levels will be measured by the Elecsys 2010 (Roche Diagnostics, Indianapolis, IN) in a dedicated core laboratory.	7 days
Secondary	Serum TxB2 (biomarker of platelet activation)	Serum Thromboxane (Tx) B2 will be measured on blood samples obtained at admission, after 72 hours and at hospital discharge (within 7 days).	7 days
Secondary	sP-selectin (biomarker of platelet activation).	Plasma sP-selectin will be measured on blood samples obtained at admission, after 72 hours and at hospital discharge (within 7 days).	7 days
Secondary	sCD40L (biomarker of platelet activation).	Plasma sCD40L will be measured on blood sample obtained at admission, after 72 hours and at hospital discharge (within 7 days).	7 days
Secondary	High-sensitivity C-Reactive Protein	Serum high-sensitivity C-Reactive Protein will be measured in blood samples obtained at admission, after 72 hours and at hospital discharge (within 7 days).	7 days
Secondary	Serum sNOX2-dp (biomarker of oxidative stress)	Serum sNOX2-dp will be measured on blood samples obtained at admission, after 72 hours and at hospital discharge (within 7 days). Blood levels of soluble NOX2-derived peptide (sNOX2-dp), a marker of NADPH oxidase activation, will be detected by ELISA as previously described (Pignatelli P et al Arterioscler Thromb Vasc Biol 2010;30:360-7).	7 days
Secondary	Serum F2-isoprostanes (biomarker of oxidative stress)	Serum F2-isoprostane (8-iso-PGF2a -III) will be measured by the enzyme immunoassay method in blood samples obtained at admission, after 72 horus and at hospital discharge (within 7 days).	7 days
Secondary	Urinary F2-isoprostanes (biomarker of oxidative stress)	F2-isoprostanes will be measured in urine samples collected at admission, after 72 horus and at hospital discharge (within 7 days).	7 days
Secondary	Cardiovascular events during hospitalization.	This composite outcome will consist in any of the following events during hospitalization: acute myocardial infarction, new or worsening heart failure, new onset atrial fibrillation, stroke, cardiovascular death.	7 days
Secondary	Major adverse cardiac and cerebrovascular events (MACCE) at 30 days.	This composite outcome will consist in any of the following events during a 30-days follow-up: cardiovascular death, myocardial infarction and stroke.	30 days
Secondary	Major adverse cardiac and cerebrovascular events (MACCE) during a a long-term follow-up.	This composite outcome will consist in any of the following events during a 2-years f follow-up: cardiovascular death, myocardial infarction and stroke.	2 years
Secondary	Short-term mortality	Death for any cause during a 30-days follow-up	30 days
Secondary	Long-term mortality	Death for any cause during a2 years follow-up	2 years