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

NCT00391911 | Completed Phase 2

• 2 other identifiers: RHABDO 2006Health Canada Control # 108739
• Study Type: interventional
• Target: 3
• Locations: 2 countries
• Sites: 2

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

Conditions

Rhabdomyolysis

Keywords

Rhabdomyolysis; CRRT; N-Acetylcysteine

Outcome Measures

Primary Outcomes (1)

• The primary outcome measures include serial measurements of markers of renal glomerular function and damage and markers of renal tubular function and damage

  day 1-28

Secondary Outcomes (2)

• Secondary outcome measures include all-cause ICU mortality and hospital mortality, ICU and hospital length of stay.

  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.

  at day 28

Study Arms (4)

NAC and CRRT

ACTIVE COMPARATOR

N-Acetylcysteine and CRRT Patients are assigned to N-Acetylcysteine and CRRT. The N-Acetylcysteine is blinded to everyone except pharmacy. The CRRT is open label,

Drug: N-Acetylcysteine

NAC and non CRRT

OTHER

Patients are assigned to N-Acetylcysteine and CRRT. The N-Acetylcysteine is blinded to everyone except pharmacy. The CRRT is open label as would be impossible to blind

Other: N-Acetylcystine and Non CRRT

Placebo and CRRT

OTHER

Patients are assigned to placebo treatment and CRRT. The N-Acetylcysteine/placebo is blinded to everyone except pharmacy. The CRRT is open label.

Other: Placebo and CRRT

Placebo and Non CRRT

OTHER

Patients are assigned to Placebo and non-CRRT. This is the standard of care arm. The N-Acetylcysteine/placebo is blinded to everyone except pharmacy. The CRRT/non CRRT is open label as would be impossible to blind

Other: Placebo and Non CRRT

Interventions

N-Acetylcysteine DRUG

Patients are assigned to either N-Acetylcysteine or placebo. Dose is weight based Placebo is normal saline or D5W

Also known as: NAC

NAC and CRRT

N-Acetylcystine and Non CRRT OTHER

Patients are assigned to N-Acetylcysteine and CRRT. The N-Acetylcysteine is blinded to everyone except pharmacy. The CRRT is open label as would be impossible to blind

Also known as: NAC only

NAC and non CRRT

Placebo and CRRT OTHER

Patients are assigned to Placebo and CRRT. The N-Acetylcysteine/Placebo is blinded to everyone except pharmacy. The CRRT is open label

Also known as: Placebo

Placebo and CRRT

Placebo and Non CRRT OTHER

Patients are assigned to Placebo and non-CRRT. The N-Acetylcysteine/placebo is blinded to everyone except pharmacy. The CRRT/non CRRT is open label as would be impossible to blind

Also known as: Placebo - no CRRT

Placebo and Non CRRT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Randomization within 96 hours of medical or surgical diagnosis consistent with rhabdomyolysis
• \>18 yrs old
• Meeting any one of the following (estimated ARF risk \>20% )
• CK \>25,000 IU/L
• Injury Severity Score \>16 and CK \>5000 IU/L
• Age \>55 and CK \>5000 IU/L
• Clinical suspicion of high probability of developing acute renal failure
• Informed consent

You may not qualify if:

• Allergic reaction to N-acetylcysteine.
• Previous wish not to include dialysis as part of medical therapy.
• Clinical and biochemical indications for dialysis or ultrafiltration at the time of screening:
• Massive fluid overload unresponsive to diuretics and requiring ultrafiltration.
• Refractory acidosis with a persistent serum pH \< 7.20 despite HCO3 therapy.
• Hyperkalemia with EKG changes necessitating dialysis for the removal of potassium.
• Pericardial friction rub from uremic pericarditis.
• RIFLE category Failure defined by one of:
• Increase serum creatinine x 3, GFR decrease 75% OR
• SCreat ≥ 4mg/dl (354 umol/L) (acute rise ≥ 0.5mg/dl \[44 umol/L\])
• UO \< 0.3ml/kg/h x 24h or anuria x 12 hours
• RIFLE category Loss - persistent ARF =complete loss of kidney function \> 4 weeks
• Pregnancy

Sponsors & Collaborators

• Royal Alexandra Hospital: lead
• University of Alberta: collaborator
• Gambro Renal Products, Inc.: collaborator

Study Sites (2)

Royal Alexandra Hospital

Edmonton, Alberta, T5H 3V9, Canada

Location

King Fahad National Guard Hospital

Riyadh, 11426, Saudi Arabia

Location

Related Publications (6)

• Abul-Ezz SR, Walker PD, Shah SV. Role of glutathione in an animal model of myoglobinuric acute renal failure. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9833-7. doi: 10.1073/pnas.88.21.9833.

  PMID: 1946409 BACKGROUND

• Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D, Zidek W. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med. 2000 Jul 20;343(3):180-4. doi: 10.1056/NEJM200007203430304.

  PMID: 10900277 BACKGROUND

• Briguori C, Manganelli F, Scarpato P, Elia PP, Golia B, Riviezzo G, Lepore S, Librera M, Villari B, Colombo A, Ricciardelli B. Acetylcysteine and contrast agent-associated nephrotoxicity. J Am Coll Cardiol. 2002 Jul 17;40(2):298-303. doi: 10.1016/s0735-1097(02)01958-7.

  PMID: 12106935 BACKGROUND

• Sochman J. N-acetylcysteine in acute cardiology: 10 years later: what do we know and what would we like to know?! J Am Coll Cardiol. 2002 May 1;39(9):1422-8. doi: 10.1016/s0735-1097(02)01797-7.

  PMID: 11985902 BACKGROUND

• Birck R, Krzossok S, Markowetz F, Schnulle P, van der Woude FJ, Braun C. Acetylcysteine for prevention of contrast nephropathy: meta-analysis. Lancet. 2003 Aug 23;362(9384):598-603. doi: 10.1016/S0140-6736(03)14189-X.

  PMID: 12944058 BACKGROUND

• Ward MM. Factors predictive of acute renal failure in rhabdomyolysis. Arch Intern Med. 1988 Jul;148(7):1553-7.

  PMID: 3382301 BACKGROUND

MeSH Terms

Conditions

Rhabdomyolysis

Interventions

Acetylcysteine; N-monoacetylcystine

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Demetrios J. Kutsogiannis, M.D.

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD MHS FRCPC

Study Record Dates

• First Submitted: October 24, 2006
• First Posted: October 25, 2006
• Study Start: November 1, 2006
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: March 5, 2012

Record last verified: 2012-03

Locations

CA (1); SA (1)