Clinical trial NCT00241228: Haemofiltration Study : IVOIRE (hIgh VOlume in Intensive Care)
Official title: Impact of High-volume Veno-venous Continuous Hemofiltration in the Early Management of Septic Shock Patients With Acute Renal Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Shock, Septic
Renal Failure, Acute
Keywords: Shock, Septic
Renal Failure, Acute
Venovenous Hemofiltration
Randomized Controlled Trial
Multicenter Study
Mortality
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2005-10-18
Enrollment: 139
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: all-cause mortality.
timeFrame: 28-day
Secondary outcomes:
measure: Haemodynamic parameters and volume loading
timeFrame: Every 12 hours during 96 hours after inclusion
measure: Doses and duration of catecholamine infusions
timeFrame: Every 12 hours during 96 hours after inclusion
measure: Organ failures
timeFrame: During 96 hours after inclusion
measure: Duration of mechanical ventilation
timeFrame: Total during the stay in intensive care
measure: Duration of renal replacement therapy
timeFrame: Total during the stay in Intensive Care Unity (ICU)
measure: Morbidity
timeFrame: Total during the stay in intensive care
measure: Length of stay in ICU and hospital
timeFrame: End of hospitalization
measure: Mortality
timeFrame: in ICU (96 first hours after inclusion), 60 and 90-day
Other outcomes:
Locations:
city: Bruxelles (Neder Over Hembeek)
country: Belgium
facility: Astrid Queen Military Hospital
city: Bruxelles
country: Belgium
facility: Cliniques de l'Europe
city: La Louviere
country: Belgium
facility: TIVOLI Hospital
city: Liege
country: Belgium
facility: University Hospital
city: Ottignies-Louvain-La-Neuve
country: Belgium
facility: St-Pierre Para-University Hospital
city: Agen
country: France
facility: Hospital
city: Bordeaux
country: France
facility: Clinic Bordeaux Nord
city: Brest
country: France
facility: University Hospital
city: Grenoble
country: France
facility: University Hospital
city: Libourne
country: France
facility: Hospital R Boulin - Libourne
city: Lyon
country: France
facility: University Hospital
city: Paris
country: France
facility: Aphp - Hegp
city: Pessac
country: France
facility: Service d'Anesthésie-Réanimation II, Groupe Hospitalier Sud, CHU de Bordeaux
city: Tourcoing
country: France
facility: Hospital
city: Delf
country: Netherlands
facility: Hospital
city: Heerlen
country: Netherlands
facility: Hospital
Study officials:
affiliation: University Hospital, Bordeaux, France
name: Olivier JOANNES-BOYAU, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Quuen Astrid Military Hospital, BRUXELLES - Belgium
name: Patrick HONORE, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Bordeaux, France
name: Paul Perez, Dr
role: STUDY_CHAIR
References:
citation: 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.