Haemofiltration Study : IVOIRE (hIgh VOlume in Intensive Care) (IVOIRE)

Impact of High-volume Veno-venous Continuous Hemofiltration in the Early Management of Septic Shock Patients With Acute Renal Failure

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.

Study Overview

• Status: Completed
• Conditions: Shock, Septic; Renal Failure, Acute
• Intervention / Treatment: Device: Venovenous haemofiltration (renal replacement therapy); Device: Venovenous haemofiltration (renal replacement therapy)

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.

• Study Type: Interventional
• Enrollment (Actual): 139
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium
    • Cliniques de l'Europe
  • Bruxelles (Neder Over Hembeek), Belgium
    • Astrid Queen Military Hospital
  • La Louviere, Belgium
    • TIVOLI Hospital
  • Liege, Belgium
    • University Hospital
  • Ottignies-Louvain-La-Neuve, Belgium
    • St-Pierre Para-University Hospital
• France
  • Agen, France, 47923
    • Hospital
  • Bordeaux, France, 33077
    • Clinic Bordeaux Nord
  • Brest, France, 29200
    • University Hospital
  • Grenoble, France, 38600
    • University Hospital
  • Libourne, France, 33505
    • Hospital R Boulin - Libourne
  • Lyon, France, 69317
    • University Hospital
  • Paris, France, 75908
    • Aphp - Hegp
  • Pessac, France, 33604
    • Service d'Anesthésie-Réanimation II, Groupe Hospitalier Sud, CHU de Bordeaux
  • Tourcoing, France, 59209
    • Hospital
• Netherlands
  • Delf, Netherlands
    • Hospital
  • Heerlen, Netherlands
    • Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• septic shock (Bone criteria) for less than 24 hours
• RIFLE criteria : injury or worse
• age over 18 years
• written informed consent by next of kin.

Exclusion Criteria:

• cirrhosis
• age over 80 years
• life expectancy less than 3 months or metastatic cancer
• for women : pregnancy and breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: High Volume; ultra filtration : High volume : 70 ml/kg/h	Device: Venovenous haemofiltration (renal replacement therapy); High Volume ultra filtration (70 ml/kg/h); Device: Venovenous haemofiltration (renal replacement therapy); Conventional Volume (35 ml/kg/h)
ACTIVE_COMPARATOR: Medium Volume; Ultra filtration : conventional volume : 35 ml/kg/h	Device: Venovenous haemofiltration (renal replacement therapy); High Volume ultra filtration (70 ml/kg/h); Device: Venovenous haemofiltration (renal replacement therapy); Conventional Volume (35 ml/kg/h)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
all-cause mortality.	28-day

Secondary Outcome Measures

Outcome Measure	Time Frame
Haemodynamic parameters and volume loading	Every 12 hours during 96 hours after inclusion
Doses and duration of catecholamine infusions	Every 12 hours during 96 hours after inclusion
Organ failures	During 96 hours after inclusion
Duration of mechanical ventilation	Total during the stay in intensive care
Duration of renal replacement therapy	Total during the stay in Intensive Care Unity (ICU)
Morbidity	Total during the stay in intensive care
Length of stay in ICU and hospital	End of hospitalization
Mortality	in ICU (96 first hours after inclusion), 60 and 90-day

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Collaborators: Ministry of Health, France
• Investigators: Principal Investigator: Olivier JOANNES-BOYAU, Dr, University Hospital, Bordeaux, France; Principal Investigator: Patrick HONORE, Dr, Quuen Astrid Military Hospital, BRUXELLES - Belgium

Publications and helpful links

General Publications

• Joannes-Boyau O, Honore PM, Perez P, Bagshaw SM, Grand H, Canivet JL, Dewitte A, Flamens C, Pujol W, Grandoulier AS, Fleureau C, Jacobs R, Broux C, Floch H, Branchard O, Franck S, Roze H, Collin V, Boer W, Calderon J, Gauche B, Spapen HD, Janvier G, Ouattara A. High-volume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial. Intensive Care Med. 2013 Sep;39(9):1535-46. doi: 10.1007/s00134-013-2967-z. Epub 2013 Jun 6.

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (ACTUAL): October 1, 2010
• Study Completion (ACTUAL): October 1, 2010

Study Registration Dates

• First Submitted: October 17, 2005
• First Submitted That Met QC Criteria: October 17, 2005
• First Posted (ESTIMATE): October 18, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): October 13, 2010
• Last Update Submitted That Met QC Criteria: October 12, 2010
• Last Verified: October 1, 2010

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; Mortality; Shock, Septic; Multicenter Study; Renal Failure, Acute; Venovenous Hemofiltration
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Kidney Diseases; Urologic Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Renal Insufficiency; Acute Kidney Injury
• Other Study ID Numbers: 9410-04; 2004-024