Study protocol

A randomized clinical trial of unfractioned heparin for treatment of sepsis (the HETRASE study): design and rationale [NCT00100308]

Fabián Jaimes¹ , Gisela De La Rosa² , Clara Arango² , Fernando Fortich² , Carlos Morales³ , Daniel Aguirre⁴ and Pablo Patiño⁵

¹  Associate Professor, Department of Internal Medicine and Grupo Académico de Epidemiología Clínica, School of Medicine, Universidad de Antioquia, Medellín, Colombia. Doctoral candidate, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

²  Assistant Professor, Department of Internal Medicine, School of Medicine, Universidad de Antioquia, Medellín, Colombia

³  Professor, Department of Surgery and Grupo Académico de Epidemiología Clínica, School of Medicine, Universidad de Antioquia, Medellín, Colombia

⁴  Associate Researcher, Grupo Académico de Epidemiología Clínica, School of Medicine, Universidad de Antioquia, Medellín, Colombia

⁵  Professor, Department of Microbiology and Grupo de Inmunodeficiencias Primarias, School of Medicine, Universidad de Antioquia, Medellín, Colombia

author email corresponding author email

Trials 2006, 7:19doi:10.1186/1745-6215-7-19

Published:	26 May 2006

Abstract

Introduction

Infection promotes coagulation via a large number of molecular and cellular mechanisms, and this procoagulant activity has boosted basic and clinical research using anticoagulant molecules as therapeutic tools in sepsis. Heparin, which is a naturally occurring proteoglycan that acts by reducing thrombin generation and fibrin formation, has not been rigorously tested in a randomized clinical trial.

Methods

Randomized, double-masked, placebo-controlled, single-center clinical trial. Patients are recruited through the emergency room at Hospital Universitario San Vicente de Paul. This is a 650-bed University Hospital in Medellín, Colombia and is a referral center for a region with approximately 3 million habitants. The recruitment process started on July 2005 and will finish on June 2007. Patients aged 18 years or older, males or females, hospitalized with clinically or microbiological confirmed sepsis, have been included. The interventions are unfractioned heparin in low dose continuous infusion (500 units per hour for 7 days) or placebo, additionally to the standard of care for sepsis patients in Colombia.

Results

Our primary aims are to estimate the effects of heparin on hospital length of stay and change from baseline Multiple Organ Dysfunction (MOD) score. Secondary objectives are to estimate the effects of heparin on 28-day all-cause mortality, and to estimate the possible effect modification on 28-day all-cause mortality, in subgroups defined by source and site of infection, and baseline values of APACHE II score, MOD score and D-dimer.

Conclusion

The available literature in animal and human research, and the understanding of the molecular biology regarding inflammation and coagulation, supports a randomized clinical trial for the use of heparin in sepsis. Our study will provide appropriate power to detect differences in valid surrogate outcomes, and it will explore important preliminary data for efficacy regarding the clinical end-point of mortality.