Community-acquired PneumoniaPhase 3COLOSSEUMNCT03745664
Corticosteroids and Myocardial Injury in CAP (COLOSSEUM TRIAL)
A Phase 3 study testing Methylprednisolone Sodium Succinate and Saline Solution for Injection in people with Community-acquired Pneumonia, run by University of Roma La Sapienza at 1 site in Italy.
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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Community-acquired Pneumonia
- What is being tested?
- Methylprednisolone Sodium Succinate and Saline Solution for Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 122 participants
- Where
- 1 siteItaly
- Study dates
- 10 Jan 2021to 1 Sep 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Hospitalization for community-acquired pneumonia
Who cannot join
- Use of corticosteroids in the previous 30 days
- Health Care-Associated Pneumonia
- Reported severe immunosuppression (human immunodeficiency virus infection, immunosuppressive conditions or medications)
- Preexisting medical condition with a life expectancy of less than 3 months
- Uncontrolled diabetes mellitus
- Gastritis with or without major gastrointestinal bleeding within 3 months
- Any condition requiring acute treatment with glucocorticoids
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Sapienza University of Rome
Rome, 00161
Francesco Violi, Full Prof, +39-06-4461933, francesco.violi@uniroma1.it
Lorenzo Loffredo, MD, +39-06-49970103, lorenzo.loffredo@uniroma1.it
About this study
Official title: Effect of Corticosteroids On MyocardiaL Injury Among Patients Hospitalized for Community-AcquirEd PneUMonia - COLOSSEUM TRIAL
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.
Read the 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.
- Conditions
- Community-acquired Pneumonia
- Being tested
- Methylprednisolone Sodium Succinate, Saline Solution for Injection
- Keywords
- corticosteroids
- Medical subject headings
- Community-Acquired Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylprednisolone Sodium SuccinateDrug
During hospitalization, 40 mg of methylprednisolone (20 mg/ml) will be given intravenously twice a day (20 mg every 12 hours).
Saline Solution for InjectionDrug
During hospitalization, 2 ml of Saline Solution for Injection will be given intravenously twice a day (2 ml every 12 hours).
| Study group | Role | What they receive |
|---|---|---|
| Treatment group | Active comparator | 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). Receives: Drug: Methylprednisolone Sodium Succinate |
| Placebo group | Placebo comparator | 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). Receives: Drug: Saline Solution for Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 7 days
Secondary outcomes (12)
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).
Measured: 7 days
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).
Measured: 7 days
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).
Measured: 7 days
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).
Measured: 7 days
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).
Measured: 7 days
Serum F2-isoprostanes (biomarker of oxidative stress)
Serum F2-isoprostane (8-iso-PGF2α -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).
Measured: 7 days
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).
Measured: 7 days
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.
Measured: 7 days
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.
Measured: 30 days
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.
Measured: 2 years
Short-term mortality
Death for any cause during a 30-days follow-up
Measured: 30 days
Long-term mortality
Death for any cause during a2 years follow-up
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2018
- Study start10 Jan 2021
- Primary completion16 May 2023 (estimated)
- Study completion1 Sep 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Community-acquired PneumoniaStudies of the same condition, open and under way.
- More trials run by University of Roma La SapienzaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Phase 3, multicenter, double-blind, placebo-controlled, randomized, intervention trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 122 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Roma La Sapienza
- Sponsor type
- University, hospital or other
- Collaborators
- Azienda Policlinico Umberto I
- Responsible party
- Principal investigator, Francesco Violi, University of Roma La Sapienza
- Investigators
- Francesco Violi, MD, Study chair, University of Roma La SapienzaRoberto Cangemi, Study director, University of Roma La Sapienza
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03745664
- Sponsor's protocol ID
- COLOSSEUM trial - Rif 5133
- Acronym
- COLOSSEUM
- Status last verified
- Sep 2021
- First submitted
- 14 Nov 2018
- Last updated
- 30 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 25444147Cangemi 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.
PubMed 30188173Cangemi 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.
PubMed 29577968Liverani 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.
PubMed 22366284
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Corticosteroids On MyocardiaL Injury Among Patients Hospitalized for Community-AcquirEd PneUMonia - COLOSSEUM TRIAL
- ClinicalTrials.gov ID
- NCT03745664
- Acronym / sponsor ID
- COLOSSEUM / COLOSSEUM trial - Rif 5133
- Conditions
- Community-acquired Pneumonia
- Keywords
- corticosteroids
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 122 participants (estimated)
- Lead sponsor
- University of Roma La SapienzaUniversity, hospital or other
- Collaborators
- Azienda Policlinico Umberto I
- Study start
- 10 Jan 2021 (actual)
- Primary completion
- 16 May 2023 (estimated)
- Study completion
- 1 Sep 2024 (estimated)
- First posted
- 19 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Phase 3, multicenter, double-blind, placebo-controlled, randomized, intervention trial
| Arm | Type | Receives |
|---|---|---|
| Treatment group | Active comparator | Drug: Methylprednisolone Sodium SuccinateMethylprednisolone 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). |
| Placebo group | Placebo comparator | Drug: Saline Solution for InjectionSaline 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). |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Hospitalization for community-acquired pneumonia
Key exclusion criteria (7 listed)
- Use of corticosteroids in the previous 30 days
- Health Care-Associated Pneumonia
- Reported severe immunosuppression (human immunodeficiency virus infection, immunosuppressive conditions or medications)
- Preexisting medical condition with a life expectancy of less than 3 months
- Uncontrolled diabetes mellitus
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methylprednisolone Sodium SuccinateDuring hospitalization, 40 mg of methylprednisolone (20 mg/ml) will be given intravenously twice a day (20 mg every 12 hours). | Drug | Treatment group |
| Saline Solution for InjectionDuring hospitalization, 2 ml of Saline Solution for Injection will be given intravenously twice a day (2 ml every 12 hours). | Drug | Placebo group |
Primary outcome
High sensitivity cardiac T troponin (myocardial injury biomarker)
Time frame: 7 days
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.
12 secondary outcomes
Serum TxB2 (biomarker of platelet activation)
Time frame: 7 days
sP-selectin (biomarker of platelet activation).
Time frame: 7 days
sCD40L (biomarker of platelet activation).
Time frame: 7 days
High-sensitivity C-Reactive Protein
Time frame: 7 days
Serum sNOX2-dp (biomarker of oxidative stress)
Time frame: 7 days
Serum F2-isoprostanes (biomarker of oxidative stress)
Time frame: 7 days
Urinary F2-isoprostanes (biomarker of oxidative stress)
Time frame: 7 days
Cardiovascular events during hospitalization.
Time frame: 7 days
Major adverse cardiac and cerebrovascular events (MACCE) at 30 days.
Time frame: 30 days
Major adverse cardiac and cerebrovascular events (MACCE) during a a long-term follow-up.
Time frame: 2 years
Short-term mortality
Time frame: 30 days
Long-term mortality
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2021.
- Background: PubMed 25444147Cangemi 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.
- Background: PubMed 30188173Cangemi 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.
- Background: PubMed 29577968Cangemi 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.
- Background: PubMed 22366284Liverani 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francesco Violi, MD study chair
University of Roma La Sapienza
Roberto Cangemi study director
University of Roma La Sapienza
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Methylprednisolone Sodium Succinate and Saline Solution for Injection in people with Community-acquired Pneumonia, run by University of Roma La Sapienza at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Francesco Violi, MD (064461933 ext. +39, francesco.violi@uniroma1.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
High sensitivity cardiac T troponin (myocardial injury biomarker) (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03745664, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2021.