Haemofiltration Study : IVOIRE (hIgh VOlume in Intensive Care)
Condition: Shock, Septic; Renal Failure, Acute
MeSH terms: Shock, Septic; Renal Insufficiency; Acute Kidney Injury; Shock
Study type: Interventional

Summary: 
      Sepsis and septic shock are still important causes of mortality in intensive care medicine.
      Renal replacement therapy by standard volume haemofiltration is currently used, but a
      higher-volume haemofiltration may improve the prognosis. The study is a prospective
      randomized multicenter trial comparing two treatments in patients suffering from septic shock
      complicated with acute renal failure admitted to ICU. One group will be treated by early high
      volume haemofiltration (70 ml/kg/h) and the second group by standard volume haemofiltration
      (35 ml/kg/h). The main outcome will be one-month mortality.
    

Detailed description: 
      Background

      Sepsis and septic shock are still important causes of mortality in intensive care medicine
      nowadays. Mortality ranges from 40 up to 80 % depending on the number of organ failures.
      Therapeutic strategy consists of two major components: haemodynamic stabilization with
      restoration of adequate arterial pressure and optimization of peripheral perfusion delivery,
      and infection treatment. Mortality remains high despite the use of new antimicrobial therapy
      and adjuvant therapies such as activated protein C, low dose corticoids and haemofiltration.
      Initial observations in patients with acute renal failure treated by haemofiltration showed
      azotemia control, restoration of the sodium-water balance, elimination of inflammatory
      mediators and improvement of the cardiac and pulmonary functions was demonstrated
      independently of a negative water balance. There is no human randomized study so far
      demonstrating these preliminary findings. Nevertheless, several authors have demonstrated
      inflammatory mediators elimination by the use of haemofiltration. Moreover, the clinical
      improvement seems to be related to the ultra filtration dose and to the early initiation of
      therapy. Joannes-Boyau et al carried out a pilot study in abdominal surgery patients
      demonstrating that the use of high volume haemofiltration in patients with septic shock and
      multiple organ failure restores hemodynamic stability with drastic reductions in
      catecholamine requirements and a substantial reduction of observed vs. expected mortality.

      Objectives

      The principal objective of the study is to evaluate the effect of early Continuous High
      Volume Haemofiltration on 28-day mortality in patients with septic shock complicated by acute
      renal failure. The secondary objectives are to assess the effect of High Volume
      Haemofiltration on haemodynamics, doses of catecholamines, organ failures, duration of
      mechanical ventilation, duration of renal replacement therapy need, morbidity, length of ICU
      and hospital stay, and 60- and 90-day mortality.

      Study design

      Open label randomized multicenter controlled trial on two parallel groups of patients with
      septic shock and acute renal failure admitted to ICU, treated early either by high volume (70
      ml/kg/h) or by standard volume (35 ml/kg/h) haemofiltration.

      Eligibility criteria

      Inclusion criteria. Septic shock (Bone criteria) for less than 24 hours, RIFLE criteria :
      injury or worse, age over 18 years, and written informed consent by next of kin. Non
      inclusion criteria. Cirrhosis, age over 80 years, life expectancy less than 3 months or
      metastatic cancer.

      Intervention

      High volume (70 ml/kg/h) vs. standard volume (35 ml/kg/h) haemofiltration during 96 hours.
      Further renal replacement therapy (if haemofiltration, only standard volume is allowed) may
      be used according to investigator decision.

      Primary endpoint

      All cause 28-day mortality.

      Statistical aspects

      460 patients are planned to be included (230 in each group). A 15 % absolute reduction in
      28-days all-cause mortality in the high volume group compared with the standard group is
      expected. However, as this reduction might be greater, an interim analysis is planned when
      half of the total sample size will have been included. Data will be analyzed on an
      intention-to-treat basis.

      Duration of the study: 3 years.
    

Intervention name(s): Venovenous haemofiltration (renal replacement therapy); Venovenous haemofiltration (renal replacement therapy)
Intervention type(s): Device; Device
Intervention description(s): High Volume ultra filtration (70 ml/kg/h); Conventional Volume (35 ml/kg/h)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Shock, Septic; Renal Failure, Acute; Venovenous Hemofiltration; Randomized Controlled Trial; Multicenter Study; Mortality