Haemofiltration Study : IVOIRE (hIgh VOlume in Intensive Care)

Sponsor

University Hospital, Bordeaux (Other)

Overall Status

Completed

CT.gov ID

NCT00241228

Collaborator

Ministry of Health, France (Other)

139

Enrollment

Locations

Arms

Duration (Months)

8.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Shock, Septic Renal Failure, Acute	Device: Venovenous haemofiltration (renal replacement therapy) Device: Venovenous haemofiltration (renal replacement therapy)	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

139 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2005

Actual Primary Completion Date :

Oct 1, 2010

Actual Study Completion Date :

Oct 1, 2010

Arms and Interventions

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)
Active Comparator: Medium Volume Ultra filtration : conventional volume : 35 ml/kg/h	Device: Venovenous haemofiltration (renal replacement therapy) Conventional Volume (35 ml/kg/h)

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)

Active Comparator: Medium Volume

Ultra filtration : conventional volume : 35 ml/kg/h

Device: Venovenous haemofiltration (renal replacement therapy)

Conventional Volume (35 ml/kg/h)

Outcome Measures

Primary Outcome Measures

all-cause mortality. [28-day]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Astrid Queen Military Hospital	Bruxelles (Neder Over Hembeek)	Belgium
2	Cliniques de l'Europe	Bruxelles	Belgium
3	TIVOLI Hospital	La Louviere	Belgium
4	University Hospital	Liege	Belgium
5	St-Pierre Para-University Hospital	Ottignies-Louvain-La-Neuve	Belgium
6	Hospital	Agen	France	47923
7	Clinic Bordeaux Nord	Bordeaux	France	33077
8	University Hospital	Brest	France	29200
9	University Hospital	Grenoble	France	38600
10	Hospital R Boulin - Libourne	Libourne	France	33505
11	University Hospital	Lyon	France	69317
12	Aphp - Hegp	Paris	France	75908
13	Service d'Anesthésie-Réanimation II, Groupe Hospitalier Sud, CHU de Bordeaux	Pessac	France	33604
14	Hospital	Tourcoing	France	59209
15	Hospital	Delf	Netherlands
16	Hospital	Heerlen	Netherlands

Sponsors and Collaborators

University Hospital, Bordeaux
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
Study Chair: Paul Perez, Dr, University Hospital, Bordeaux, France