Clinical Trial: Study of N-Acetylcysteine (NAC) and Continuous Renal Replacement Therapy (CRRT) for the Treatment of Rhabdomyolysis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomized Factorial Trial of N-Acetylcysteine and Continuous Veno-Venous Hemo(Dia)Filtration for Rhabdomyolysis

Brief Summary:

Rhabdomyolysis has many causes including trauma, muscle crush injuries, lack of blood supply to an arm or leg, burns, seizures, drugs and hereditary disorders. Rhabdomyolysis causes the breakdown of muscle cells and the release of a molecule called myoglobin. Myoglobin is very harmful to the kidneys and can lead to kidney failure.

Continuous dialysis has been shown to remove the myoglobin molecule from the blood in patients with rhabdomyolysis. N-Acetylcysteine (NAC) has been used in patients receiving contrast dye for x-rays and has shown less worsening of kidney function compared to patients not receiving NAC.

Early and aggressive treatment of patients with rhabdomyolysis with standard therapy, continuous dialysis and a drug called N-acetylcysteine (NAC) may prevent the development of acute kidney failure. Patients who develop kidney failure from this disorder are often critically ill and have a much higher chance of not surviving than those who do not develop kidney failure.

The purpose of this study is to determine if the use of NAC and Continuous Veno-Venous hemo(dia)filtration (CRRT)early in the course of rhabdomyolysis (in addition to standard therapy)decreases the chance of developing acute renal failure


Detailed Summary:

Rhabdomyolysis may be defined as a clinical or biochemical syndrome which may result from a large variety of diseases, trauma, or toxic insults to skeletal muscle. The damage to the integrity of the sarcolemma of skeletal muscle leads to the release of potentially toxic muscle cell components into the circulation, specifically myoglobin into the plasma.

The three main principals of therapy for myoglobinuric renal failure include 1) correction of hypovolemia/ renal ischemia, 2) increase the clearance of heme proteins from both the circulation and the kidneys, 3) attenuate the adverse effects of heme proteins on the proximal tubule epithelium. Consequently, therapy for rhabdomyolysis is limited to aggressive rehydration with Ringer's lactate or normal saline, forced diuresis with mannitol, and urinary alkalinization with intravenous bicarbonate.

Hypothesis

  1. The use of N-acetylcysteine (NAC) and continuous veno-venous hemo(dia)filtration (CRRT) early in the course of rhabdomyolysis as an adjunct to 'standard therapy' (rehydration, mannitol diuresis, systemic alkalinization) respectively decreases the nephrotoxicity and improves elimination of systemic myoglobin. Consequently both therapies independently prevent the deterioration of renal glomerular and tubular function and establishment of acute renal failure.
  2. There exists a positive interaction between the use of N-acetylcysteine and CRRT in the prevention of acute renal failure secondary to rhabdomyolysis.

Objectives Primary objective is to compare creatinine and myoglobin clearance as well as the glomerular filtration rate over the course of 192 hours in patients with rhabdomyolysis treated with NAC, ea
Sponsor: Royal Alexandra Hospital

Current Primary Outcome: The primary outcome measures include serial measurements of markers of renal glomerular function and damage and markers of renal tubular function and damage [ Time Frame: day 1-28 ]

Original Primary Outcome: The primary outcome measures include serial measurements of markers of renal glomerular function and damage and markers of renal tubular function and damage

Current Secondary Outcome:

  • Secondary outcome measures include all-cause ICU mortality and hospital mortality, ICU and hospital length of stay. [ Time Frame: ICU admission until hospital discharge ]
  • Renal specific outcomes will include the development of Renal Failure, Loss or End Stage Kidney Disease based on the RIFLE classification system. [ Time Frame: at day 28 ]


Original Secondary Outcome:

  • Secondary outcome measures include all-cause ICU mortality and hospital mortality, ICU and hospital length of stay.
  • Renal specific outcomes will include the development of Renal Failure, Loss or End Stage Kidney Disease based on the RIFLE classification system.


Information By: Royal Alexandra Hospital

Dates:
Date Received: October 24, 2006
Date Started: November 2006
Date Completion:
Last Updated: March 1, 2012
Last Verified: March 2012