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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Peiman Nazerian, Azienda Ospedaliero-Universitaria Careggi
ClinicalTrials.gov Identifier:
NCT01908231
First received: July 23, 2013
Last updated: February 15, 2014
Last verified: February 2014
  Purpose

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


Condition
Pulmonary Embolism

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Prognostic Value of Plasma Lactate Levels Among Patients With Acute Pulmonary Embolism: the Thrombo-Embolism Lactate Outcome Study

Resource links provided by NLM:


Further study details as provided by Azienda Ospedaliero-Universitaria Careggi:

Primary Outcome Measures:
  • The composite of PE related death or hemodynamic collapse [ Time Frame: 7 days. ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • all cause death [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • PE recurrence [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 330
Study Start Date: December 2012
Study Completion Date: February 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Pulmonary Embolism
Consecutive adult patients (minimum age eighteen) who presented to the ED of the hospitals participating in the study with clinical suspicion of PE will be considered for the study. We excluded patients with life expectancies of less than 3 months, and patients with first symptoms 15 days or more before inclusion.

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Consecutive adult patients (minimum age eighteen) who presented to the ED of the hospitals participating in the study with clinical suspicion of PE will be considered for the study. We excluded patients with life expectancies of less than 3 months, and patients with first symptoms 15 day or more before inclusion.

The diagnosis of PE will be established by spiral computed tomography or by lung scan or a selective pulmonary angiogram.

Patients with proven PE who will give written consent to the use of their medical information for research purposes will be enrolled in the study.

Criteria

Inclusion Criteria:

  • Symptomatic objective pulmonary embolism

Exclusion Criteria:

  • life expectancies of less than 3 months
  • first symptoms 15 day or more before inclusion.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01908231

Locations
Italy
Azienda Ospedaliero Universitaria Careggi, Emergency Department
Florence, Italy, 50134
Presidio Ospedaliero Livorno
Livorno, Italy
Azienda ospedaliera universitaria San Giovanni Battista (Molinette)
Torino, Italy
Spain
Respiratory Department and Medicine Department, Ramón y Cajal Hospital and Alcalá de Henares University
Madrid, Spain
Sponsors and Collaborators
Azienda Ospedaliero-Universitaria Careggi
Investigators
Study Chair: Stefano Grifoni, MD Emergency department, Azienda Ospedaliero Universitaria Careggi
  More Information

Publications:

Responsible Party: Peiman Nazerian, Simone Vanni, MD, PhD, Azienda Ospedaliero-Universitaria Careggi
ClinicalTrials.gov Identifier: NCT01908231     History of Changes
Other Study ID Numbers: 0313
Study First Received: July 23, 2013
Last Updated: February 15, 2014
Health Authority: Italy: Ethics Committee

Keywords provided by Azienda Ospedaliero-Universitaria Careggi:
Pulmonary embolism, plasma lactate, right ventricular dysfunction

Additional relevant MeSH terms:
Embolism
Pulmonary Embolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on April 20, 2014