Study Comparing High Cut-off Haemofiltration With Standard Haemofiltration in Acute Renal Failure

Study Overview
=================
Brief Summary
-----------------
This trial aims to study the effect of combining continuous and a new polyamide membrane with larger pores in the treatment of critically ill patients with acute renal failure and low blood pressure (shock) requiring noradrenaline. The investigators wish to compare the clinical effect of this new therapy to that of haemofiltration with a standard membrane.

Detailed Description
-----------------
During acute renal failure, small and middle molecular-weight toxins accumulate. These molecules are difficult to remove by standard haemofiltration. Accordingly, they accumulate and contribute to morbidity in long-term dialysis patients. Molecules such as cytokines have been shown to play a central pathogenic role in critical illness. In critically ill acute renal failure patients, they accumulate in serum and likely contribute to much morbidity (fever, low blood pressure, myocardial dysfunction, renal failure itself etc.) Therefore, the removal of cytokines appears desirable. Although different approaches have been undertaken, all have had limited success due to complexity, limited efficacy or uncertain clinical response [10-15]. It is possible that in using a different and more porous membrane, the removal of cytokines would be much more efficient and that clinical benefits of blood purification would, therefore, be greater. A membrane of this kind is now available. It is a modification (moderate increase in pore size) of another standard material called polyamide, which has already been used in millions of people for dialysis and haemofiltration. The increased pore size of these new membranes is directed at a more effective removal of middle molecular-weight toxins such as cytokines.

Official Title
-----------------
Pilot Randomised Controlled Study Comparing The Effect of High Cut-off Point Haemofiltration With Standard Haemofiltration In Patients With Acute Renal Failure

Conditions
-----------------
Kidney Failure, Acute, Shock

Intervention / Treatment
-----------------
* Device: Standard polyamide high flux membrane
* Device: High cut-off (super high flux) polyamide membrane


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The treating clinician believes that the patient requires haemofiltration for acute renal failure The patient is on noradrenaline infusion for haemodynamic support The patient was commenced on noradrenaline or haemofiltration within the last 12 hours The clinician is uncertain about the balance of benefits and risks likely to be conferred by treatment with different membranes The treating clinicians anticipate treating the patient with haemofiltration for at least 72 hours Informed consent has been obtained The patient fulfils ONE of the following clinical criteria for initiating haemofiltration: Oliguria (urine output < 100 ml/6 hr) that has been unresponsive to fluid resuscitation measures. Hyperkalemia ([K+] > 6.5 mmol/L) Severe acidemia (pH < 7.2) Urea > 25 mmol/liter Creatinine > 300 mmol/L Clinically significant organ oedema in the setting of ARF (e.g., lung) Exclusion Criteria: Patient age is < 18 years Death is imminent (< 24 hours) There is a strong likelihood that the study treatment would not be continued in accordance with the study protocol The patient has been treated with haemofiltration or other dialysis previously during the same hospital admission The patient was on maintenance dialysis prior to the current hospitalisation Any other major illness that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in this study The patient is pregnant or is breastfeeding The patient has previously been enrolled in this study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>CVVH with high cut-off polyamide membrane (P2SH) using standard continuous veno-venous hemofiltration (CVVH) settings | Device: High cut-off (super high flux) polyamide membrane<br>* CVVH with standard haemofiltration settings; blood flow 200 ml/min, ultrafiltrate 25 ml/kg/hour, anticoagulation as clinically indicated, bicarbonate-buffered replacement fluid<br>* Other names: Super high flux membrane;|
| Active Comparator: 2<br>CVVH using standard high flux membrane with standard CVVH settings | Device: Standard polyamide high flux membrane<br>* Standard haemofiltration; CVVH; blood flow 200 ml/min, ultrafiltrate 25 ml/kg/hr, anticoagulation as clinically indicated, bicarbonate buffered replacement fluid<br>* Other names: High flux membrane;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome measure for this study is noradrenaline free time in the first week after randomization |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in the levels of each of three key cytokines; IL-1, IL-6 and IL-10 |  | 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Kidney failure, acute, Shock, Toxins, biological, Hemofiltration, High cut off/super high flux membranes