Preop Hemodialysis or Intraop Ultrafiltration for Patients With Severe Renal Dysfunction Undergoing Open Heart Surgery (SeRenaD-CPB)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2008 by University Hospital, Geneva.
Recruitment status was  Not yet recruiting
Sponsor:
Collaborators:
University of Gaziantep
Ankara University
Pamukkale University
German Heart Institute
Hospices Civils de Lyon
Hospital Clinic of Barcelona
Information provided by:
University Hospital, Geneva
ClinicalTrials.gov Identifier:
NCT00720967
First received: July 21, 2008
Last updated: July 22, 2008
Last verified: July 2008
  Purpose

The purpose of this study is to determine whether preoperative hemodialysis or intraoperative modified ultrafiltration are effective for patients with non-dialysis dependent severe renal dysfunction undergoing open heart surgery.


Condition Intervention Phase
Non-Dialysis Dependent Severe Renal Dysfunction
Cardiovascular Disease
Procedure: Open Heart Surgery (OHS)
Procedure: Intraoperative Modified Ultrafiltration (MUF)
Procedure: Hemodialysis (HD)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Influence of Preoperative Hemodialysis or Intraoperative Modified Ultrafiltration on Postoperative Outcome for Patients With Severe Renal Dysfunction Undergoing Open Heart Surgery: Randomized, Controlled, Multicenter Clinical Trial

Resource links provided by NLM:


Further study details as provided by University Hospital, Geneva:

Primary Outcome Measures:
  • Operative mortality, defined as any death occurring within 30 days after the operation or any death occurring before discharge during the same hospitalization (in percentage). [ Time Frame: within the first 30 days after surgery or before the discharge after surgery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Survival at one year after surgery (in percentage). [ Time Frame: one year after surgery ] [ Designated as safety issue: No ]
  • Postoperative low cardiac output (in percentage). [ Time Frame: within the first 30 days after surgery or before the discharge after surgery ] [ Designated as safety issue: No ]
  • Postoperative permanent neurological deficit (in percentage). [ Time Frame: within the first 30 days after surgery or before the discharge after surgery ] [ Designated as safety issue: No ]
  • Postoperative transient neurological deficit (in percentage). [ Time Frame: within the first 30 days after surgery or before the discharge after surgery ] [ Designated as safety issue: No ]
  • Postoperative acute renal dysfunction (in percentage). [ Time Frame: within the first 30 days after surgery or before the discharge after surgery ] [ Designated as safety issue: No ]
  • Postoperative persistent renal dysfunction requiring hemodialysis (in percentage). [ Time Frame: within the first 30 days after surgery or before the discharge after surgery ] [ Designated as safety issue: No ]
  • Postoperative gastrointestinal complication (in percentage). [ Time Frame: within the first 30 days after surgery or before the discharge after surgery ] [ Designated as safety issue: No ]
  • Postoperative respiratory failure (in percentage). [ Time Frame: within the first 30 days after surgery or before the discharge after surgery ] [ Designated as safety issue: No ]
  • Postoperative systemic infection (in percentage). [ Time Frame: within the first 30 days after surgery or before the discharge after surgery ] [ Designated as safety issue: No ]
  • Postoperative local infection (in percentage). [ Time Frame: within the first 30 days after surgery or before the discharge after surgery ] [ Designated as safety issue: No ]
  • Postoperative new-onset arrythmia (in percentage). [ Time Frame: within the first 30 days after surgery or before the discharge after surgery ] [ Designated as safety issue: No ]
  • Postoperative surgical drainage (in mL). [ Time Frame: within the first 72 hours after surgery ] [ Designated as safety issue: No ]
  • Postoperative need for transfusion of blood products (in unit packs). [ Time Frame: within the first 72 hours after surgery ] [ Designated as safety issue: No ]
  • Postoperative length of ICU stay (in days) [ Time Frame: within the first 30 days after surgery or before the discharge after surgery ] [ Designated as safety issue: No ]
  • Postoperative length of hospital stay (in days) [ Time Frame: within the first 30 days after surgery or before the discharge after surgery ] [ Designated as safety issue: No ]
  • Total hospital costs for the admission of operation (in Euros) [ Time Frame: From the day of admission to hospital until the day of discharge after surgery ] [ Designated as safety issue: No ]

Estimated Enrollment: 450
Study Start Date: November 2008
Estimated Study Completion Date: November 2012
Estimated Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Control Group (Open heart surgery alone)
Procedure: Open Heart Surgery (OHS)
General anesthesia, use of iodine impregnated adhesive dressing, median sternotomy and/or thoracotomy incision, full heparinization (300-400 ui/kg), arterial and venous cannulation, initialization of CPB with or without aortic cross-clamping and high-potassium cold cardioplegia, surgical repair under mild-moderate hypothermia. De-clamping (if cross clamp was applied), neutralization of heparin by protamin, de-cannulation and hemostasis after surgical repair. Insertion of drain(s) and pacing wire(s). Closure of all layers in anatomical plan.
Experimental: 2
Intraoperative Modified Ultrafiltration (MUF) Group (Open heart surgery with intraoperative MUF)
Procedure: Open Heart Surgery (OHS)
General anesthesia, use of iodine impregnated adhesive dressing, median sternotomy and/or thoracotomy incision, full heparinization (300-400 ui/kg), arterial and venous cannulation, initialization of CPB with or without aortic cross-clamping and high-potassium cold cardioplegia, surgical repair under mild-moderate hypothermia. De-clamping (if cross clamp was applied), neutralization of heparin by protamin, de-cannulation and hemostasis after surgical repair. Insertion of drain(s) and pacing wire(s). Closure of all layers in anatomical plan.
Procedure: Intraoperative Modified Ultrafiltration (MUF)
Once the surgical repair is finished, and CPB will be stopped after aortic declamping. The arterial and venous cannulae will be connected to each other using 3-way connectors and a cardioplegia line. When hemodynamic stability is established (MAP >75 mmHg, CVP > 12 mmHg, Htc > 25%), blood will be drained from the arterial cannula using a roller pump, driven to the ultrafilter, and eventually to the venous cannula. The blood flow will be maintained at ~150 mL/min, and suction will be applied to the filtrate port to achieve an ultrafiltration of 100-120 mL/min. Heat exchanger and bubble trap of the cardioplegia line will be used to maintain the filtered blood at body temperature and to prevent air embolism, respectively. MUF will continue 20 minutes. The filtered volume will be collected.
Experimental: 3
Preoperative Hemodialysis Group (Open Heart Surgery after preoperative hemodialysis)
Procedure: Open Heart Surgery (OHS)
General anesthesia, use of iodine impregnated adhesive dressing, median sternotomy and/or thoracotomy incision, full heparinization (300-400 ui/kg), arterial and venous cannulation, initialization of CPB with or without aortic cross-clamping and high-potassium cold cardioplegia, surgical repair under mild-moderate hypothermia. De-clamping (if cross clamp was applied), neutralization of heparin by protamin, de-cannulation and hemostasis after surgical repair. Insertion of drain(s) and pacing wire(s). Closure of all layers in anatomical plan.
Procedure: Hemodialysis (HD)
Two HD sessions will be performed at 3 days and 1 day prior to surgery. Each session will last 3 hours if the patient weighs < 75 kg, and 4 hours if > 75 kg. Conventional HD will be carried out using a volume-controlled dialysis machine. A bicarbonate dialysate containing K (3 mmol/L), Ca (1.5 mmol/L) and HCO3 (31 mmol/L) will be used. Sodium conductivity will be set at 138 mmol/L. Medium-flow filters will be used as artificial kidney devices. Dialysate temperature will be set at 36oC. Dialysate and blood flow rate will be set at 500 mL/min and 250-300 ml/min, respectively. Intradialytic ultrafiltration will not be used routinely unless the patient has volume overload. The decision to use intradialytic ultrafiltration will be taken with the anaesthesiologist and the cardiac surgeon. If intradialytic ultrafiltration is indicated, maximal rate of ultrafiltration will be 10 ml/kg/hour. These patients will undergo open heart surgery after two sessions of HD.

  Hide Detailed Description

Detailed Description:

1. BACKGROUND

1.1. RENAL DYSFUNCTION AND OPEN HEART SURGERY:

The incidences of both cardiovascular disease (CVD) and chronic renal dysfunction (RD) are increasing with the aging population in the western world (1). The intense relationship between the pathogenesis of CVD and chronic RD has recently been reviewed by Schiffrin et al, in detail (2). They both have common risk factors such as diabetes, hypertension, activation of renin-angiotensin system, endothelial dysfunction, oxydative stress, etc. Besides, each has an impact on the other's outcome. On the one hand, CVD is the most frequent cause of death in chronic RD patients (3). On the other hand, even mild chronic RD is one of the major risk factors of postoperative mortality and morbidity after cardiac operations (4, 5). The mechanism is not clear yet, however, volume overload, electrolyte imbalance and inflammatory state created by cardiopulmonary bypass (CPB) may have an impact. Zakeri et al showed that in-hospital mortality after isolated primary coronary artery bypass grafting (CABG) increases exponentially with increasing levels of renal dysfunction (6). They reported an in-hospital mortality of 2.2%, 4.3%, 9.3% and 14.8% in patients who have a preoperative serum creatinine level (SCr) of <130 µmol/L, 130-149 µmol/L, 150-179 µmol/L and 180-199 µmol/L, respectively. These results were similar to the study published previously by Weerasinghe et al with the same cut-off levels of SCr (7). Using the Glomerular Filtration Rate (GFR) instead of SCr, Cooper et al. came to the same conclusion after analysing 483,914 patients receiving isolated CABG in the Society of Thoracic Surgeons (STS) National Adult Cardiac Database (5). They reported that operative mortality rose inversely with declining renal function, from 1.3% for those with normal renal function to 1.8%, 4.3% and 9.3% for patients with mild, moderate and severe RD, respectively. Another study regarding the effect of preoperative RD on mortality after valve surgery was also published with a relatively smaller patient population (8). Although the RD group had significantly worse outcomes with regard to postoperative ventilation time, re-operation, blood transfusion and length of hospital stay, operative mortality was not statistically different between the two groups (3.4% for RD group vs. 2.3% for the control group), probably because of small sample size. However, Filsoufi et al. reported an increased mortality for patients having SCr of >2.5 mg/dL after single valve replacement (25.0% vs. 2.4%),multiple valve replacement (26.7% vs. 3.4%), and combined valve replacement with CABG (28.0% vs. 4.6%) in a large, single-center cohort (9). Regarding long-term survival, Devbhandari reported 1-, 3- and 5-year survival rates following on-pump coronary bypass surgery as 90.3%, 83.2% and 71.4% for non-dialysis dependent renal dysfunction (NDDRD) patients, and 97.4%, 94.6% and 91.0% for patients with no history of RD, respectively (10). Chronic RD affects not only the operative mortality, but also the morbidity after open heart surgery. It has been shown that preoperative RD is an independent predictor of postoperative acute RD and hemodialysis (HD) (5, 7, 9-12) as well as gastrointestinal (GI) (4, 9), respiratory (5, 9), infectious (5) and neurological (5) complications.

1.2. HEMODIALYSIS:

HD is the most common renal replacement therapy for decades, for those who have end-stage RD and have not received renal transplantation. Intermittent HD is a very efficient method to decrease blood urea and creatinine as well as to treat volume overload. Intermittent HD can be performed temporarily in the setting of acute RD or permanently in the setting of chronic RD. In chronic RD, 3 sessions of 4 hours are usually prescribed to adequately substitute the renal function. A good vascular access is essential to perform HD. A temporary dual- or tri-lumen dialysis catheter has to be inserted into a central vein such as the internal jugular, the subclavian or the femoral vein.

1.3. ULTRAFILTRATION:

Intraoperative ultrafiltration has been used widely in pediatric open heart surgery for decades, reducing total body water, increasing hematocrit (Htc) levels, removing inflammatory mediators, thus improving the operative outcome (13). In the 90's, Naik et al. modified the technique (14), and reported better outcomes with modified ultrafiltration (MUF) in pediatric population (15). However, use of MUF has been limited to end-stage RD patients with volume overload undergoing open heart surgery, as an adjunct to pre- and postoperative HD in the adult population. The Verona group reported fewer respiratory, neurological, GI complications, and less blood product transfusion in the group of patients who received MUF after CPB, however mortality, overall morbidity, length of Intensive Care Unit (ICU) stay and length of hospital stay were comparable between MUF and control groups including 573 consecutive patients (16). A meta-analysis evaluating the effects of ultrafiltration on postoperative blood product use and perioperative bleeding in adult patients revealed fewer bleeding complications and reduced blood product use after intraoperative ultrafiltration (17). Boga et al reported improved cardiac performance after CABG surgery with MUF. However, they could not find any difference in Interleukin-6, Interleukin-8 and Neopterin levels. They attributed this effect to prevention of hemodilution and hypervolemia (18). In summary, no clear evidence is available at the present regarding the impact of intraoperative MUF on the operative outcome of NDDRD patients undergoing open heart surgery. Capuano et al. recently (19) reported successful results in a NDDRD patient who required urgent coronary revascularisation. Nevertheless, the impact of intraoperative MUF on the outcome of NDDRD patients undergoing open heart surgery remains unclear, and is worth investigation.

1.4. PREVIOUS STUDIES:

The quest to improve the outcome of NDDRD patients undergoing open heart surgery has been in the agenda of some groups to date. Two pioneering studies were recently published from Turkey (20, 21). The target patient population was NDDRD patients undergoing elective isolated primary CABG surgery. Patients were randomized into two groups prospectively, one group received 2 doses of prophylactic HD just before surgery whereas the other did not, and served as control. Both studies reported reduced operative mortality rates, reduced postoperative need for HD, and shorter length of stay in the prophylactic HD groups. However, these two studies had very limited number of patients with a short period of follow-up, excluded valve surgery, and did not analyse cost-effectiveness. Furthermore, intraoperative ultrafiltration was not studied.

1.5. ASSESSMENT OF RENAL FUNCTION:

GFR is the best measure of overall kidney function (22). The Cockroft-Gault formula is a commonly used way to predict GFR (23). GFR <30 mL/min/1.73 m2 is accepted as "severe RD" (22). SCr is a simple and practical universal biologic marker used for estimating glomerular filtration. Although SCr does not have a linear association with GFR, it has also been reported to be a powerful predictor of operative mortality (6). Thus, SCr and GFR were both accepted as preoperative indicators of RD with the cut-off levels of 180 µmol/L (or 2.0 mg/dL) and 30 mL/min/1.73 m2, respectively.

1.6. CONCLUSION:

In summary, this data mandates us a well defined strategy for patients with NDDRD in order to obtain better operative outcome. Under the guidance of the current literature, a randomized controlled trial (RCT) with a larger number of patients undergoing open heart surgery will provide precise answers for these questions. Comparison of hospital costs may add an extra value for the assessment of cost-effectiveness as well.

  Eligibility

Ages Eligible for Study:   18 Years to 95 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 years or older
  • Diagnosis of SCr > 180 µmol/L or 2.0 mg/dL, and/or a GFR < 30 mL/min/1.73 m2.
  • Indication for elective open heart surgery under CPB.

Exclusion Criteria:

  • History of chronic or recent HD.
  • Emergency status.
  • Off-pump surgery.
  • Failure to obtain patient consent documented by a signed consent form.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00720967

Contacts
Contact: Erman Pektok, MD +41.76.3169990 epektok@hotmail.com
Contact: Patrick O. Myers, MD +41.22.3727630 patrick.myers@hcuge.ch

Locations
France
University of Lyon, Hopital Cardiothoracique Louis Pradel Not yet recruiting
Lyon, France
Contact: Jean-Francois I. Obadia, MD, PhD    +33.4.75357546    jean-francois.obadia@chu-lyon.fr   
Principal Investigator: Jean-Francois I. Obadia, MD, PhD         
Germany
German Heart Institute Berlin Not yet recruiting
Berlin, Germany, D-13353
Contact: Roland Hetzer, MD    +49.30.45932000    hetzer@dhzb.de   
Principal Investigator: Roland Hezter, MD         
Sub-Investigator: Boris Nasseri, MD         
Sub-Investigator: Sabine Huebler, MD         
Sub-Investigator: Semih Buz, MD         
Spain
Hospital Clinico, University of Barcelona, Department of Cardiovascular Surgery Not yet recruiting
Barcelona, Spain
Contact: Carlos A. Mestres, MD, PhD    +34.93.2275515    cmestres@clinic.ub.es   
Principal Investigator: Carlos A. Mestres, MD, PhD         
Switzerland
University Hospital of Geneva, Service for Cardiovascular Surgery Not yet recruiting
Geneva, Switzerland, 1211
Contact: Erman Pektok, MD    +41.76.3169990    epektok@hotmail.com   
Contact: Patrick O. Myers, MD    +41.22.3727630    patrick.myers@hcuge.ch   
Principal Investigator: Erman Pektok, MD         
Sub-Investigator: Patrick O. Myers, MD         
Sub-Investigator: Ebrahim Khabiri, MD         
Sub-Investigator: Mustafa Cikirikcioglu, MD, PhD         
Sub-Investigator: Pierre-Yves Martin, MD, PhD         
Sub-Investigator: Afksendiyos Kalangos, MD, PhD         
Turkey
Ankara University, Department of Cardiovascular Surgery Not yet recruiting
Ankara, Turkey, 06340
Contact: Ruchan Akar, MD    +90.312.5082202    akarruchan@gmail.com   
Principal Investigator: Ruchan Akar, MD         
Sub-Investigator: Serkan Durdu, MD         
Sub-Investigator: Levent Yazicioglu, MD         
Sub-Investigator: Sim Kutlay, MD         
Sub-Investigator: Sadik Eryilmaz, MD         
Sub-Investigator: Mustafa Sirlak, MD         
Pamukkale University, Department of Cardiovascular Surgery Not yet recruiting
Denizli, Turkey, 20070
Contact: Gokhan Onem, MD    +90.258.4440728 ext 2294    gonem@pau.edu.tr   
Principal Investigator: Gokhan Onem, MD         
Sub-Investigator: Mustafa Sacar, MD         
Sub-Investigator: Belda Dursun, MD         
Gaziantep University, Department of Cardiovascular Surgery Not yet recruiting
Gaziantep, Turkey, 27310
Contact: Hasim Ustunsoy, MD    +90.342.3603910    hustunsoy@yahoo.com   
Principal Investigator: Hasim Ustunsoy, MD         
Sub-Investigator: Celaleddin Usalan, MD         
Sub-Investigator: Oktay Burma, MD         
Sponsors and Collaborators
University Hospital, Geneva
University of Gaziantep
Ankara University
Pamukkale University
German Heart Institute
Hospices Civils de Lyon
Hospital Clinic of Barcelona
Investigators
Principal Investigator: Erman Pektok, MD University Hospital of Geneva, Service for Cardiovascular Surgery
Study Director: Patrick O Myers, MD University Hospital of Geneva, Service for Cardiovascular Surgery
Study Director: Thomas Perneger, MD, PhD University Hospital of Geneva, Center of Clinical Research
Study Chair: Afksendiyos Kalangos, MD, PhD University Hospital of Geneva, Service for Cardiovascular Surgery
  More Information

Publications:

Responsible Party: Erman Pektok, MD, University Hospital of Geneva, Service for Cardiovascular Surgery
ClinicalTrials.gov Identifier: NCT00720967     History of Changes
Other Study ID Numbers: 08-058 (NAC 08018)
Study First Received: July 21, 2008
Last Updated: July 22, 2008
Health Authority: Switzerland: Ethikkommission
Turkey: Ethics Committee
Germany: Ethics Commission
France: Institutional Ethical Committee
Spain: Ethics Committee

Keywords provided by University Hospital, Geneva:
Renal dysfunction
Hemodialysis
Modified ultrafiltration
Open heart surgery

Additional relevant MeSH terms:
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 22, 2014