Clinical trial NCT03058211: Myocardial Injury and Severe Pneumococcal Pneumonia
Official title: Myocardial Injury in Severe Pneumococcal Pneumonia as a Cause of Mortality From Acute Cardiovascular Events
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Pneumonia, Pneumococcal
Myocardial Ischemia
Keywords: Pneumococcal pneumonia
Acute cardiovascular events
Lead sponsor: Hospital Universitari Joan XXIII de Tarragona.
Sponsor class: OTHER
First posted: 2017-02-20
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Critically ill patients admitted to the intensive care unit due to severe community-acquired pneumonia

Brief summary: Hypothesis: The "novo" cardiovascular events (CVE)in patients with severe community-acquired pneumonia (CAP) are frequent (17%) and could be associated with both direct pneumococcal myocardial invasion, toxin delivery (pneumolysin) or different biomarkers (histones, NETs(neutrophil extracellular traps), IL (Interleukin)-1b,h-Fabp (heart-Fatty acid bindding protein) ).The CVE frequency and its impact on outcome in patients without prior heart disease (CP) has not been studied.

Objectives:1) To determine the incidence of myocardian injury (MI) and CVE in patients with CAP without CP evaluated by non-invasive techniques (Echocardiograph and MRI) and biomarkers levels (Tn-I (Troponin I), h-Fabp, NT-proBNP (N-terminal pro-brain natriuretic peptide) histones, NETs, IL 1b); 2) To assess if DMA and CVE are related to the etiology and their impact on outcome , 3) To investigate the presence of myocardial scarring by MRI and its relationship with etiology and MI, and 4) To identify prognostic factors of DMA and CVE to determine level of risk.

Detailed description: Area: Intensive care unit (ICU) of the participating hospitals. Patients: Forty patients with CAP without heart disease history will be included consecutively (20 patients with pneumococcal CAP and 20 patients with non-pneumococcal CAP).Ten healthy volunteers (controls) are included.

Variables: Epidemiological, clinical and hemodynamic variables are recorded. Presence of MI and CVE measured by echocardiography and by biomarkers will be evaluated during the ICU stay. Presence of scarring miocardic by MRI technique will be determined at month 6 since ICU admission.

Statistical analysis: Categorical (Fisher's exact test) and continuous variables( Wilconxon and Anova) will be used to determine differences between them. The Pearson correlation, ROC (discriminatory power) and logistic regression analysis(independent association) will be used to determine the association between variables and outcome. A p-value of 0.05 will be considered significant.

Eligibility criteria: Inclusion Criteria:

1. - Patients admitted to the ICU due to community-acquired pneumonia according to IDSA/ATS criteria
2. - No history of heart diasese
3. - Informed consent signed

Exclusion Criteria:

1. - Hospital or ventilator-associated pneumonia
2. - Health care-associated pneumonia
3. - Viral pneumonia
4. - Bacterial/viral coinfection pneumonia
5. - History of heart disease
6. - Chronic administration of statins
7. - Chronic administration of steorids (Prednisolone more 20 mg/day or equivalent)
8. - No signed informed consent

Primary outcomes:
measure: Myocardian injury (scarring) in patients with CAP without cardiac disease (CP)history at 6 months of ICU admission
timeFrame: at 6 months
measure: Heart dysfunction in patients with CAP without cardiac disease (CP)history in the first week of ICU admission
timeFrame: at day 7 of ICU admission)
Secondary outcomes:
measure: Temporal profile of the Troponin I as a cardiac injury biomarker in patients with CAP without cardiac disease (CP)history in the first week of ICU admission
timeFrame: once per day ( days 1 to 7 of ICU admission)
measure: Temporal profile of the N-terminal pro-brain natriuretic peptide(NT-proBNP) as a cardiac injury biomarker in patients with CAP without cardiac disease (CP)history in the first week of ICU admission
timeFrame: once per day (days 1 to 7 of ICU admission)
measure: Temporal profile of the heart- fatty acid binding protein (h-Fabp) as a cardiac injury biomarker in patients with CAP without cardiac disease (CP)history in the first week of ICU admission
timeFrame: once per day (days 1 to 7 of ICU admission)
Other outcomes:
Locations:
city: Tarragona
country: Spain
facility: Critical Care Department - Hospital Universitario de Tarragona Joan XXIII
Study officials:
affiliation: Hospital Universitari de Tarragona Joan XXIII
name: Alejandro H Rodriguez Oviedo
role: PRINCIPAL_INVESTIGATOR
References:
citation: Corrales-Medina VF, Musher DM, Shachkina S, Chirinos JA. Acute pneumonia and the cardiovascular system. Lancet. 2013 Feb 9;381(9865):496-505. doi: 10.1016/S0140-6736(12)61266-5. Epub 2013 Jan 16.
citation: Alhamdi Y, Neill DR, Abrams ST, Malak HA, Yahya R, Barrett-Jolley R, Wang G, Kadioglu A, Toh CH. Circulating Pneumolysin Is a Potent Inducer of Cardiac Injury during Pneumococcal Infection. PLoS Pathog. 2015 May 14;11(5):e1004836. doi: 10.1371/journal.ppat.1004836. eCollection 2015 May.
citation: Brown AO, Mann B, Gao G, Hankins JS, Humann J, Giardina J, Faverio P, Restrepo MI, Halade GV, Mortensen EM, Lindsey ML, Hanes M, Happel KI, Nelson S, Bagby GJ, Lorent JA, Cardinal P, Granados R, Esteban A, LeSaux CJ, Tuomanen EI, Orihuela CJ. Streptococcus pneumoniae translocates into the myocardium and forms unique microlesions that disrupt cardiac function. PLoS Pathog. 2014 Sep 18;10(9):e1004383. doi: 10.1371/journal.ppat.1004383. eCollection 2014 Sep.
citation: Lee YJ, Lee H, Park JS, Kim SJ, Cho YJ, Yoon HI, Lee JH, Lee CT, Park JS. Cardiac troponin I as a prognostic factor in critically ill pneumonia patients in the absence of acute coronary syndrome. J Crit Care. 2015 Apr;30(2):390-4. doi: 10.1016/j.jcrc.2014.12.001. Epub 2014 Dec 4.