Prognostic Value of Plasma Lactate Levels Among Patients With Acute Pulmonary Embolism

Pulmonary Embolism Clinical Trial

— TELOS  

Official title:

Prognostic Value of Plasma Lactate Levels Among Patients With Acute Pulmonary Embolism: the Thrombo-Embolism Lactate Outcome Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01908231
• Other study ID #: 0313
• Status: Completed
• Phase: N/A
• First received: July 23, 2013
• Last updated: February 15, 2014
• Start date: December 2012
• Est. completion date: February 2014

Study information

• Verified date: February 2014
• Source: Azienda Ospedaliero-Universitaria Careggi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Observational

Clinical Trial Summary

To prospectively investigate the association between plasma lactate concentration and short-term adverse outcomes in patients with acute PE.

Description:

Pulmonary embolism (PE) represents 0.4% of hospitalizations and is the third leading cause of death due to cardiovascular disease (1). In contrast to stroke and acute coronary syndromes, its mortality has not decreased in recent decades likely due to only minor advances in short-term prognostication and treatment strategies (2).The presence of shock or hypotension remains the principal prognostic clinical marker and,to date, is the only factor that clearly indicates a more aggressive treatment than heparin (3). However, only 5% of patients with acute PE present with shock. The majority of PE patients are normotensive and are usually treated with heparin alone. Several studies have looked for new prognostic indicators in order to better stratify normotensive PE patients. A large body of evidence shows that right ventricular dysfunction/injury markers such as elevation of brain natriuretic peptides, troponins, and echocardiographic evidence of right ventricular dysfunction (RVD) are associated with adverse prognosis (3-8). However, these markers have some important limitations. Echocardiography is usually not available around-the-clock in most clinical settings, moreover it shares with troponins and natriuretic peptides a good negative predictive value (>90%) but a low positive predictive value (about 10%) for short-term mortality, probably precluding these markers' usefulness to target more aggressive treatments (8).

Plasma lactate concentration is a marker of the severity of the tissue oxygen supply-to-demand imbalance. It may reflect tissue hypoperfusion also in the presence of normal blood pressure. Accordingly, in other critical settings such as sepsis,plasma lactate concentration is considered to be an accurate prognostic marker as it rises before hemodynamic impairment is clinically evident (9). Furthermore, plasma lactate concentration can be easily and rapidly assayed on arterial blood samples using a blood gas analyzer, which is usually available in emergency departments (EDs) and intensive care units. Recently, a retrospective study showed that plasma lactate ≥ 2 mmol/L was associated with a high mortality rate in patients with acute PE (10). Moreover a prospective monocentric study confirmed these retrospective results and revealed that plasma lactate has prognostic relevance beyond known clinical and instrumental prognostic markers (TELOS study, Ann Emerg Med, in press, see attached file)

The aim of present study is to prospectively investigate the association between plasma lactate concentration and short-term adverse outcomes in patients with acute PE. In particular, we examine whether high plasma lactate (≥ 2 mmol/L) is associated with a high incidence of PE related major adverse events, defined as PE related death or hemodynamic collapse >10% within 7 days of follow-up. Moreover we investigate whether plasma lactate shows incremental prognostic value to clinically overt hemodynamic impairment and to RVD/injury markers, maintaining prognostic relevance in both hypotensive and normotensive PE patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 330
• Est. completion date: February 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Symptomatic objective pulmonary embolism

Exclusion Criteria:

• life expectancies of less than 3 months

• first symptoms 15 day or more before inclusion.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Embolism
• Pulmonary Embolism

Locations

Country	Name	City	State
Italy	Azienda Ospedaliero Universitaria Careggi, Emergency Department	Florence
Italy	Presidio Ospedaliero Livorno	Livorno
Italy	Azienda ospedaliera universitaria San Giovanni Battista (Molinette)	Torino
Spain	Respiratory Department and Medicine Department, Ramón y Cajal Hospital and Alcalá de Henares University	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliero-Universitaria Careggi

Countries where clinical trial is conducted

Italy,  Spain, 

References & Publications (11)

Binder L, Pieske B, Olschewski M, Geibel A, Klostermann B, Reiner C, Konstantinides S. N-terminal pro-brain natriuretic peptide or troponin testing followed by echocardiography for risk stratification of acute pulmonary embolism. Circulation. 2005 Sep 13;112(11):1573-9. Epub 2005 Sep 6. — View Citation

Burge AJ, Freeman KD, Klapper PJ, Haramati LB. Increased diagnosis of pulmonary embolism without a corresponding decline in mortality during the CT era. Clin Radiol. 2008 Apr;63(4):381-6. doi: 10.1016/j.crad.2007.10.004. Epub 2007 Dec 21. — View Citation

Grifoni S, Olivotto I, Cecchini P, Pieralli F, Camaiti A, Santoro G, Conti A, Agnelli G, Berni G. Short-term clinical outcome of patients with acute pulmonary embolism, normal blood pressure, and echocardiographic right ventricular dysfunction. Circulation. 2000 Jun 20;101(24):2817-22. — View Citation

Grifoni S, Vanni S, Magazzini S, Olivotto I, Conti A, Zanobetti M, Polidori G, Pieralli F, Peiman N, Becattini C, Agnelli G. Association of persistent right ventricular dysfunction at hospital discharge after acute pulmonary embolism with recurrent thromboembolic events. Arch Intern Med. 2006 Oct 23;166(19):2151-6. — View Citation

Kline JA, Zeitouni R, Marchick MR, Hernandez-Nino J, Rose GA. Comparison of 8 biomarkers for prediction of right ventricular hypokinesis 6 months after submassive pulmonary embolism. Am Heart J. 2008 Aug;156(2):308-14. doi: 10.1016/j.ahj.2008.03.026. Epub 2008 Jun 18. — View Citation

Kucher N, Goldhaber SZ. Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism. Circulation. 2003 Nov 4;108(18):2191-4. Review. — View Citation

Pulido T, Aranda A, Zevallos MA, Bautista E, Martínez-Guerra ML, Santos LE, Sandoval J. Pulmonary embolism as a cause of death in patients with heart disease: an autopsy study. Chest. 2006 May;129(5):1282-7. — View Citation

Shapiro NI, Trzeciak S, Hollander JE, Birkhahn R, Otero R, Osborn TM, Moretti E, Nguyen HB, Gunnerson KJ, Milzman D, Gaieski DF, Goyal M, Cairns CB, Ngo L, Rivers EP. A prospective, multicenter derivation of a biomarker panel to assess risk of organ dysfunction, shock, and death in emergency department patients with suspected sepsis. Crit Care Med. 2009 Jan;37(1):96-104. doi: 10.1097/CCM.0b013e318192fd9d. — View Citation

Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP; ESC Committee for Practice Guidelines (CPG). Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J. 2008 Sep;29(18):2276-315. doi: 10.1093/eurheartj/ehn310. Epub 2008 Aug 30. — View Citation

Vanni S, Polidori G, Vergara R, Pepe G, Nazerian P, Moroni F, Garbelli E, Daviddi F, Grifoni S. Prognostic value of ECG among patients with acute pulmonary embolism and normal blood pressure. Am J Med. 2009 Mar;122(3):257-64. doi: 10.1016/j.amjmed.2008.08.031. — View Citation

Vanni S, Socci F, Pepe G, Nazerian P, Viviani G, Baioni M, Conti A, Grifoni S. High plasma lactate levels are associated with increased risk of in-hospital mortality in patients with pulmonary embolism. Acad Emerg Med. 2011 Aug;18(8):830-5. doi: 10.1111/j.1553-2712.2011.01128.x. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The composite of PE related death or hemodynamic collapse	PE related death was defined as a fatal event occurring in the hours after clinical deterioration due to PE, including an objectively diagnosed recurrent PE, or if death could not be attributed to a documented cause and PE could not be confidently ruled out. Autopsy is not mandatory.; Hemodynamic collapse is defined as at least 1 of the following: (i) the need for cardiopulmonary resuscitation; (ii) systolic blood pressure <90 mm Hg for at least 15 minutes, or drop of systolic blood pressure by at least 40 mm Hg for at least 15 minutes, with signs of end-organ hypoperfusion (cold extremities, or urinary output <30 mL/h, or mental confusion); (iii) the need for catecholamines (except for dopamine at a rate of < 5 µg kg-1 min-1) to maintain adequate organ perfusion and a systolic blood pressure of >90 mm Hg; (iiii) the need for invasive or noninvasive mechanical ventilation; (iiiii) imaging-confirmed symptomatic recurrence of PE within 7 days.	7 days.	No
Secondary	all cause death		30 days	No
Secondary	PE recurrence		30 days	No