Corticosteroids and Myocardial Injury in CAP (COLOSSEUM TRIAL)

NCT ID: NCT03745664

Last Updated: 2021-09-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

122 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-10

Study Completion Date

2024-09-01

Brief Summary

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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

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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.

Conditions

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Community-acquired Pneumonia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Phase 3, multicenter, double-blind, placebo-controlled, randomized, intervention trial
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Doctors, staff and any primary care provider/s involved in the participant's non-trial management will be blinded to the group allocations. Individual participants will be not told their group allocation until the end of their involvement in the trial and after the completion of the trial

Study Groups

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Treatment group

Methylprednisolone Sodium Succinate (20mg/ml) will be given at the dose of 40 mg/day (20 mg x 2/day).

The treatment will last 7 days (or the time of hospitalization if the patient is discharged in a period less or more than 7 days).

Group Type ACTIVE_COMPARATOR

Methylprednisolone Sodium Succinate

Intervention Type DRUG

During hospitalization, 40 mg of methylprednisolone (20 mg/ml) will be given intravenously twice a day (20 mg every 12 hours).

Placebo group

Saline Solution for Injection will be given ath the dose of 2 ml/day. The treatment placebo will last 7 days (or the time of hospitalization if the patient is discharged in a period less or more than 7 days).

Group Type PLACEBO_COMPARATOR

Saline Solution for Injection

Intervention Type DRUG

During hospitalization, 2 ml of Saline Solution for Injection will be given intravenously twice a day (2 ml every 12 hours).

Interventions

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Methylprednisolone Sodium Succinate

During hospitalization, 40 mg of methylprednisolone (20 mg/ml) will be given intravenously twice a day (20 mg every 12 hours).

Intervention Type DRUG

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).

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Azienda Policlinico Umberto I

OTHER

Sponsor Role collaborator

University of Roma La Sapienza

OTHER

Sponsor Role lead

Responsible Party

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Francesco Violi

Prof. Francesco Violi

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Francesco Violi, MD

Role: STUDY_CHAIR

University of Roma La Sapienza

Roberto Cangemi

Role: STUDY_DIRECTOR

University of Roma La Sapienza

Locations

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Sapienza University of Rome

Rome, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Francesco Violi, MD

Role: CONTACT

064461933 ext. +39

Roberto Cangemi, MD, PhD

Role: CONTACT

3358093936 ext. +39

Facility Contacts

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Francesco Violi, Full Prof

Role: primary

+39-06-4461933

Lorenzo Loffredo, MD

Role: backup

+39-06-49970103

References

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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.

Reference Type BACKGROUND
PMID: 25444147 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30188173 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29577968 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22366284 (View on PubMed)

Other Identifiers

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COLOSSEUM trial - Rif 5133

Identifier Type: -

Identifier Source: org_study_id

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