Community-acquired Pneumonia
Conditions
Keywords
corticosteroids
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.
Interventions
DRUGMethylprednisolone Sodium Succinate
During hospitalization, 40 mg of methylprednisolone (20 mg/ml) will be given intravenously twice a day (20 mg every 12 hours).
During hospitalization, 2 ml of Saline Solution for Injection will be given intravenously twice a day (2 ml every 12 hours).
Sponsors
Azienda Policlinico Umberto I
University of Roma La Sapienza
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
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
Intervention model description
Phase 3, multicenter, double-blind, placebo-controlled, randomized, intervention trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| High sensitivity cardiac T troponin (myocardial injury biomarker) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| sP-selectin (biomarker of platelet activation). | 7 days | Plasma sP-selectin will be measured on blood samples obtained at admission, after 72 hours and at hospital discharge (within 7 days). |
| sCD40L (biomarker of platelet activation). | 7 days | Plasma sCD40L will be measured on blood sample obtained at admission, after 72 hours and at hospital discharge (within 7 days). |
| High-sensitivity C-Reactive Protein | 7 days | 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). |
| Serum sNOX2-dp (biomarker of oxidative stress) | 7 days | 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). |
| Serum F2-isoprostanes (biomarker of oxidative stress) | 7 days | 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). |
| Serum TxB2 (biomarker of platelet activation) | 7 days | Serum Thromboxane (Tx) B2 will be measured on blood samples obtained at admission, after 72 hours and at hospital discharge (within 7 days). |
| Cardiovascular events during hospitalization. | 7 days | 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. |
| Major adverse cardiac and cerebrovascular events (MACCE) at 30 days. | 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. |
| Major adverse cardiac and cerebrovascular events (MACCE) during a a long-term follow-up. | 2 years | This composite outcome will consist in any of the following events during a 2-years f follow-up: cardiovascular death, myocardial infarction and stroke. |
| Short-term mortality | 30 days | Death for any cause during a 30-days follow-up |
| Long-term mortality | 2 years | Death for any cause during a2 years follow-up |
| Urinary F2-isoprostanes (biomarker of oxidative stress) | 7 days | F2-isoprostanes will be measured in urine samples collected at admission, after 72 horus and at hospital discharge (within 7 days). |
Countries
Italy
Contacts
Primary ContactFrancesco Violi, MD
Backup ContactRoberto Cangemi, MD, PhD
Outcome results
None listed