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

Kidney Failure, Acute Clinical Trial

— PARACHUTE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00522756
• Other study ID #: SDR-05-045
• Status: Recruiting
• Phase: Phase 3
• First received: August 29, 2007
• Last updated: October 22, 2012
• Start date: May 2006
• Est. completion date: March 2013

Study information

• Verified date: October 2012
• Source: McGill University Health Center
• Contact: Carole Albert, RN
• Phone: (514) 934-1934
• Email: carole.albert[@]muhc.mcgill.ca
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: March 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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%

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Acute Kidney Injury
• Kidney Failure, Acute
• Renal Insufficiency

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	McGill University Health Centre - Royal Victoria Hospital	Montreal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
McGill University Health Center

Country where clinical trial is conducted

Canada, 

References & Publications (1)

Merten GJ, Burgess WP, Gray LV, Holleman JH, Roush TS, Kowalchuk GJ, Bersin RM, Van Moore A, Simonton CA 3rd, Rittase RA, Norton HJ, Kennedy TP. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA. 2004 May 19;291(19):2328-34. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Increase in serum creatinine of 44 micromol/L or by 25% within the first 3 days after surgery.		3 days	No
Secondary	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	No