PARACHUTE: Preventing Acute Renal Failure After Cardiac Surgery in High Risk Patients Using Sodium Bicarbonate Therapy

Sponsor

McGill University Health Centre/Research Institute of the McGill University Health Centre (Other)

Overall Status

Unknown status

CT.gov ID

NCT00522756

Collaborator

(none)

200

Enrollment

Location

Arms

Duration (Months)

2.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether sodium bicarbonate is effective in reducing kidney injury that may occur during cardiac surgery.

Condition or Disease	Intervention/Treatment	Phase
Kidney Failure, Acute	Drug: Sodium bicarbonate Drug: Sodium chloride	Phase 3

Detailed Description

Acute renal failure (ARF) is an important complication after cardiac surgery that has a prevalence ranging between 5 and 30%. In addition, the impact of chronic kidney disease (CKD) has been well correlated with poorer outcomes after cardiac surgery. These factors have been demonstrated to be associated with increased morbidity, mortality, as well as consuming limited health care resources.

Despite the identification of certain higher risk determinants such as emergency surgery, valvular surgery, preoperative creatinine level, diabetes, increasing age, obesity, and peripheral vascular disease, interventions to decrease postoperative ARF in these patients have been limited. Agents that have been successful in other settings, such as N-acetylcysteine and fenoldopam, have shown no difference in clinical outcomes of ARF when tested in randomized clinical trials in high-risk cardiac surgery patients. Although prophylactic hemodialysis has been shown to be effective for patients with underlying severe kidney disease, this is clearly a resource intensive therapy that may not be practical as a general prophylaxis strategy.

The use of sodium bicarbonate has shown efficacy in reducing the incidence of ARF due to contrast-induced nephropathy in those patients with moderate, stable renal dysfunction. The postulated mechanism of renal protection has been described through the prevention of free radical generation and damage. The generation of a higher renal proximal tubule pH with bicarbonate therapy may slow down the superoxide-generating Haber-Weiss reaction, limiting the formation of free radical oxidants. In addition, sodium bicarbonate may be directly scavenging reactive oxygen species generated from nitric oxide, at a physiologic pH.

If it is presumed that initiation and extension of ischemic renal injury occurs during cardiac surgery via oxidant injury, the use of sodium bicarbonate to disrupt this process could possibly be an effective therapeutic option to prevent ARF.

The objective of this study is to evaluate the renal protective effect of near-isotonic sodium bicarbonate as compared to sodium chloride when given as prophylaxis to patients with chronic kidney disease prior to non-emergent surgery involving the use of cardiopulmonary bypass.

Our hypothesis is that bicarbonate therapy may disrupt ischemia-induced, oxidant-mediated injury and this may prevent the propagation of renal damage. These events may be demonstrated clinically by a reduced incidence of ARF following surgery, decreased requirements for renal replacement therapy after surgery, and improved survival both perioperatively and in a longer-term follow up.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Prevention

Official Title:

Preventing Acute Renal Failure After Cardiac Surgery in High Risk Patients Using Sodium Bicarbonate Therapy (PARACHUTE) - Pilot Study

Study Start Date :

May 1, 2006

Anticipated Primary Completion Date :

Dec 1, 2012

Anticipated Study Completion Date :

Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention Three ampoules of 7.5% sodium bicarbonate (89.3 mOsm/ampoule; total 150 ml for three ampoules) added to 750 ml of 5% dextrose in water, given at 1 ml/kg/hour through a dedicated intravenous line for 6 hours, and completed prior to the initiation of cardiopulmonary bypass.	Drug: Sodium bicarbonate Three ampoules of 7.5% sodium bicarbonate (89.3 mOsm/ampoule; total 150 ml for three ampoules) added to 750 ml of 5% dextrose in water, given at 1 ml/kg/hour through a dedicated intravenous line for 6 hours, and completed prior to the initiation of cardiopulmonary bypass. Other Names: NaHCO3
Active Comparator: Control 0.9% sodium chloride given at 1 ml/kg/hour through a dedicated intravenous line for 6 hours, and completed prior to the initiation of cardiopulmonary bypass.	Drug: Sodium chloride 0.9% sodium chloride given at 1 ml/kg/hour through a dedicated intravenous line for 6 hours, and completed prior to the initiation of cardiopulmonary bypass. Other Names: saline

Arm

Intervention/Treatment

Experimental: Intervention

Three ampoules of 7.5% sodium bicarbonate (89.3 mOsm/ampoule; total 150 ml for three ampoules) added to 750 ml of 5% dextrose in water, given at 1 ml/kg/hour through a dedicated intravenous line for 6 hours, and completed prior to the initiation of cardiopulmonary bypass.

Drug: Sodium bicarbonate

Other Names:

NaHCO3

Active Comparator: Control

0.9% sodium chloride given at 1 ml/kg/hour through a dedicated intravenous line for 6 hours, and completed prior to the initiation of cardiopulmonary bypass.

Drug: Sodium chloride

0.9% sodium chloride given at 1 ml/kg/hour through a dedicated intravenous line for 6 hours, and completed prior to the initiation of cardiopulmonary bypass.

Other Names:

saline

Outcome Measures

Primary Outcome Measures

Increase in serum creatinine of 44 micromol/L or by 25% within the first 3 days after surgery. [3 days]

Secondary Outcome Measures

Postoperative vasoactive medication, intra-aortic balloon pump, mechanical ventilation, reintubation, reoperation, myocardial infarction, stroke, infection, hypokalemia, dialysis, ICU and hospital length of stay and survival. [3 weeks post operative period]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

age greater than or equal to 18 years
elective or urgent CABG +/- valve surgery, or elective or urgent isolated valve surgery
exposure to cardiopulmonary bypass
stable kidney disease: less than 25% change in serum creatinine during 3 months before surgery
Estimated glomerular filtration rate, by Modification of Diet in Renal Disease (MDRD) equation, less than or equal to 60 ml/min/1.73m2

Exclusion criteria:

emergency CABG, cardiac transplantation, or insertion of VAD
planned off-pump surgery
N-acetylcysteine given in last 72 hours prior to operation
radiocontrast given in last 48 hours prior to operation
acute renal failure (greater than 25% increase in serum creatinine from preadmission baseline)
glomerular filtration rate less than 15 ml/min or chronic dialysis
prior renal transplantation
enrollment in another research study, with the exception of MUHC study SDR-05-033
LV ejection fraction less than or equal to 20%

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	McGill University Health Centre - Royal Victoria Hospital	Montreal	Quebec	Canada	H3A1A1

Sponsors and Collaborators

McGill University Health Centre/Research Institute of the McGill University Health Centre

Investigators

Principal Investigator: Benoit de Varennes, MD, McGill University Health Centre/Research Institute of the McGill University Health Centre
Principal Investigator: Ahsan Alam, MD, McGill University Health Centre/Research Institute of the McGill University Health Centre