Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

High Volume Veno-venous Hemofiltration Versus Standard Care for Post-cardiac Surgery Shock (HEROICS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01077349
Recruitment Status : Completed
First Posted : March 1, 2010
Last Update Posted : February 9, 2017
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date  ICMJE February 26, 2010
First Posted Date  ICMJE March 1, 2010
Last Update Posted Date February 9, 2017
Study Start Date  ICMJE December 2009
Actual Primary Completion Date January 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 26, 2010)
Death from all causes at 30 days after randomisation [ Time Frame: 30 days ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2010)
  • Mortality 60 days following study enrollment [ Time Frame: 60 days ]
  • ICU mortality [ Time Frame: 90 days ]
  • Mortality adjusted on the type of surgery and patient severity at randomization [ Time Frame: 90 days ]
  • Mortality 90 days following study enrollment [ Time Frame: 90 days ]
  • Hospital mortality [ Time Frame: 90 days ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 26, 2010)
  • Mortality 60 and 90 days following study enrollment [ Time Frame: 90 days ]
  • ICU and Hospital mortality [ Time Frame: 90 days ]
  • Mortality adjusted on the type of surgery and patient severity at randomization [ Time Frame: 90 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE High Volume Veno-venous Hemofiltration Versus Standard Care for Post-cardiac Surgery Shock
Official Title  ICMJE Early Continuous High Volume Veno-venous Hemofiltration vs. Standard Care for Post-cardiac Surgery Shock Requiring High Doses Catecholamines. The HEROICS Study: HEmofiltration to Rescue Severe shOck followIng Cardiac Surgery
Brief Summary This study seeks to determine if early continuous High Volume Veno-venous Hemofiltration (HVHF) reduces 30-day all cause mortality in post-cardiac surgery patients developing shock requiring high doses catecholamines.
Detailed Description

Study Title - Early continuous high volume veno-venous hemofiltration vs. standard care for post-cardiac surgery shock requiring high dose catecholamines. An open label randomized multicenter controlled trial. The HEROICS Study: HEmofiltration to Rescue severe shOck followIng Cardiac Surgery.

Clinical Phase - III Study Rationale - Systemic inflammatory response syndrome associated with cardiac surgery under cardiopulmonary bypass (CPB) shares many pathophysiologic features of septic shock and post-resuscitation syndrome. Since high volume hemofiltration has been shown to markedly improve hemodynamic profile and survival in these situations, there is a strong rationale for testing, with an adequately powered randomized controlled trial, this purification technique in patients developing post-cardiac surgery shock requiring high doses catecholamine.

Trial Design -

The proposed study will compare high volume hemofiltration (80 ml/kg/h or a maximum of 8L/h) for 48 hours following heart surgery to standard treatment, where extra-renal replacement therapy (CVVHDF mode, total effluent <35 ml/kg/h) will be initiated only if the following criteria are met:

  • Serum creatinine > 350 micromol/L or increase x3.0 from pre-operative value OR
  • Diuresis < 0.3 ml/kg/h for 24 hours despite adequate fluid resuscitation OR
  • Or serum urea > 36 mmol/l OR
  • Or life threatening hyperkalemia. In the experimental arm, hemofiltration will be stopped after 48h if diuresis >1500 ml without diuretics and if IV infusion of catecholamines is less than 0.1 microg/kg/min of epinephrine, 0.2 microg/kg/min of norepinephrine or the sum of epinephrine + norepinephrine/2 is less than 0.1 microg/kg/min. In other cases, hemodiafiltration (CVVHDF) will be initiated until the above objectives are reached, with equal flow rate of dialysate and reinfusion fluid, the sum of which being 35 ml/kg/h (or a maximum of 3500 ml/h).

Subject Participation - 90 days

Rationale for Number of Subjects - The study will follow a sequential analytical plan with stopping rules based on the triangular test. The expected mortality of the control group is expected to be 25% and the expected absolute mortality reduction with the experimental treatment of 12%. For 80% power and a 5% α-risk, the study characteristics, calculated with the triangular test, are as follows: a maximum of 540 subjects to be included and a 90% probability of stopping the study before 330 subjects have been included. With an inclusion rate of 120-150 patients per year, the maximum duration of the study is 2 years and 3 months and the probability of stopping the study before 18 months is 90%.

Approximate duration of Study - 27 months

Study Objective(s) Primary - The primary study outcome is death from all causes at 30 days after randomisation.

Secondary

  1. Mortality 60 and 90 days following study enrollment
  2. ICU and Hospital mortality
  3. Mortality adjusted on the type of surgery and patient severity at randomization
  4. Duration of catecholamine infusion and number of catecholamine-free days at 30 days following study enrollment
  5. Duration of renal replacement therapy and number of renal replacement therapy -free days at 30 days following study enrollment
  6. Recovery of renal failure and dialysis independent survival
  7. Duration of mechanical ventilation and number of mechanical ventilation -free days at 30 days following study enrollment
  8. SOFA score on days 1, 2 ,3 ,4 ,7 ,15 , and 30 following study enrollment
  9. Reduction in markers of overt coagulation and inflammation at days 2, 4 and 7 following study enrollment
  10. ICU and Hospital length of stay
  11. Mortality analysis according to subgroups of patients (type of surgery, severity at randomization, renal function at randomization)

Approximate Number of Subjects - 330

Approximate Number of Study Centres - 8 centres distributed in France will participate in the study.

Treatment Administration - Each participant will be randomised to receive high volume hemofiltration (CVVH, 80 ml/kg/h or a maximum of 8L/h) for 48 hours following heart surgery or standard treatment, where extra-renal replacement therapy (CVVHDF mode, total effluent <35 ml/kg/h) will be initiated only if criteria for renal failure are met.

Safety Evaluation - Safety for individual patients will be assessed on an ongoing basis by physical examination, including vital signs, outputs from dialysis machine records, laboratory assessments, and monitoring of adverse events. Overall study safety will be ensured by an Independent Data Safety Monitoring Committee, independent from all Trial investigators, which will perform ongoing review of predefined safety parameters and study conduct.

Efficacy Evaluation - Overall survival at 30 days post randomisation

Statistical Analysis - The first analysis is scheduled after the inclusion of 60 subjects. Thereafter, stopping rules are scheduled to be sequentially applied, based on the triangular test. This will allow us to stop the trial as soon as there are sufficient evidence that one of the 2 treatment strategies are more dangerous or that there was no longer a chance of demonstrating the postulated treatment difference of 12%, while controlling the risks of type I and II errors. Sequential analyses will be conducted every 20 patients. The baseline and outcome variables will be compared using Students t test, Chi squared and the Mann-Whitney U test as appropriate. Kaplan-Meier survival curves for the 30 days following randomization will be compared with a log-rank test., with survival being calculated from the date of randomization.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Shock
Intervention  ICMJE
  • Procedure: high volume hemofiltration
    (80 ml/kg/h or a maximum of 8L/h) for 48 hours following heart surgery. Hemofiltration will be stopped after 48h if diuresis >1500 ml without diuretics and if IV infusion of catecholamines is less than 0.1 microg/kg/min of epinephrine, 0.2 microg/kg/min of norepinephrine or the sum of epinephrine + nor epinephrine/2 is less than 0.1 microg/kg/min. In other cases, hemodiafiltration (CVVHDF) will be initiated until the above objectives are reached, with equal flow rate of dialysate and reinfusion fluid, the sum of which being <35 ml/kg/h (or a maximum of 3500 ml/h).
  • Procedure: standard care

    extra-renal replacement therapy (CVVHDF mode, total effluent <35 ml/kg/h or a maximum of 3500 ml/h) will be initiated only if the following criteria are met:

    • Serum creatinine > 350 micromol/L or increase x3.0 from pre-operative value OR
    • Diuresis < 0.3 ml/kg/h for 24 hours despite adequate fluid resuscitation OR
    • Or serum urea > 36 mmol/l OR
    • Or life threatening hyperkalemia
Study Arms  ICMJE
  • Experimental: high volume hemofiltration
    Intervention: Procedure: high volume hemofiltration
  • Active Comparator: standard care
    Intervention: Procedure: standard care
Publications * Combes A, Bréchot N, Amour J, Cozic N, Lebreton G, Guidon C, Zogheib E, Thiranos JC, Rigal JC, Bastien O, Benhaoua H, Abry B, Ouattara A, Trouillet JL, Mallet A, Chastre J, Leprince P, Luyt CE. Early High-Volume Hemofiltration versus Standard Care for Post-Cardiac Surgery Shock. The HEROICS Study. Am J Respir Crit Care Med. 2015 Nov 15;192(10):1179-90. doi: 10.1164/rccm.201503-0516OC.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 13, 2013)
226
Original Estimated Enrollment  ICMJE
 (submitted: February 26, 2010)
330
Actual Study Completion Date  ICMJE March 2013
Actual Primary Completion Date January 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Cardiac surgery with cardiopulmonary bypass
  2. Patient still on high doses catecholamines 3 to 24 hours following cardiac-surgical ICU admission. High doses catecholamines is defined by IV infusion of :

    1. Epinephrine >0.2 microg/kg/min or
    2. Norepinephrine >0.4 microg/kg/min or
    3. Epinephrine + (Norepinephrine /2) >0.2 microg/kg/min
    4. Cardiac assistance using ECMO/ECLS technique are considered equivalent to high doses catecholamines.
  3. Informed consent has been obtained from next of kin or when consent cannot be obtained, the intervention is randomized, and written informed consent obtained from the patient as soon as he regains consciousness. This practice is consistent with the French law for clinical research.

Exclusion Criteria:

  1. Age < 18 years
  2. Pregnancy
  3. Chronic hemodialysis prior to heart surgery
  4. Body weight >120 kg
  5. Moribund state, defined as SAPS 2 score> 90
  6. Severe underlying disease with survival expectancy of less than 8 days
  7. Decision to withhold or withdraw active therapeutics
  8. PrismaFlex machine unavailable in the unit
  9. Intravascular access with dialysis catheter impossible -
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01077349
Other Study ID Numbers  ICMJE P071223
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Alain Combes, MD PhD Assistance Publique - Hôpitaux de Paris
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date October 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP