End Stage Liver FailureNACNCT00736541
N-acetylcysteine in Liver Transplantation
A study testing N-acetylcysteine in people with End Stage Liver Failure, run by Ibtesam Hilmi at 1 site in United States.
Trial summary
N-acetylcysteine (NAC) is used to treat Tylenol toxicity. NAC is a rich source of the sulfhydryl group (SH) which is important for replenishing the body's glutathione stores. Glutathione acts as a free radical scavenger, to decrease the damage that would be caused by those toxic radicals. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- End Stage Liver Failure
- What is being tested?
- N-acetylcysteine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2004to Jan 2008
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients age of 18 years
- Patients undergoing cadaveric liver transplant for the first time
- Patients with normal serum creatinine < 1- 1.2 mg/dl or creatinine clearance 97-140 ml/min and patients with mild renal dysfunction with serum creatinine of (2-2.5 mg/dl) or creatinine clearance 85-125 ml/min
- All patients will sign informed consent
Who cannot join
- Allergy to NAC
- Patients with history of asthma
- Patient with fulminate hepatic failure
- Re-do OLT
- Simultaneous other organ transplant (i.e., pancreas, heart, and small bowel)
- Pre-existing renal failure requiring hemodialysis or continuous hemofiltration and patient refusal to participate in the study.
- Although, it is extremely uncommon for a patient with hepatic failure to become pregnant due to the pathological effect of hepatic failure on the reproductive system, the policy of Liver Transplantation Service at UPMC is to advise young female not to become pregnant while waiting for OLT. In addition the majority of the patients on the liver transplant waiting list at this institution are above 50 years of age. However, when a female patient of child-bearing potential is called in for OLT and there is a suspicion that she might be pregnant, a blood pregnancy test will be performed as a part of the standard of care for these patients.
Trial locations and contacts
1 site in 1 country.
United States1 site
Unversity of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Investigation of the Efficacy of N-acetylcysteine (NAC) to Protect Against Hepato-renal Ischemia-reperfusion Injury in Patients Undergoing Orthotopic Liver Transplantation
N-acetylcysteine (NAC) is used to treat Tylenol toxicity. NAC is a rich source of the sulfhydryl group (SH) which is important for replenishing the body's glutathione stores. Glutathione acts as a free radical scavenger, to decrease the damage that would be caused by those toxic radicals. Patients who undergo orthotopic liver transplantation (OLT) have a high incidence of post-operative renal dysfunction. The most common etiology of post-operative renal dysfunction is related to high levels of toxic free radicals. Free radicals may contribute to primary liver graft failure or delayed liver graft function.
Specific Aims \& Objectives:
The primary objective of this study is to evaluate the efficacy of NAC in improving liver graft performance and lowering the incidence of post-operative renal dysfunction. The secondary objectives are to investigate the effect of NAC on endogenous glutathione body stores and its effect on FK506 induced toxicity.
Read the detailed description
This is a randomized, double-blind placebo-controlled study that investigates the use of NAC during and after OLT. A total of 100 patients will be recruited. Fifty will receive a placebo (normal saline) and the other fifty will receive NAC. The patients in the NAC group will receive a loading dose of 140 mg/kg IV of NAC over one hour at the start of the surgery. Thereafter, NAC will be repeated every 4 hours at a dose of 70 mg/kg IV, for a total of 13 doses. The placebo group will receive an equal volume of a normal saline infusion for 13 doses. Both groups will be followed for one year after their OLT. The following data will be recorded and collected: liver function tests, renal function tests, liver graft survival rate, patient survival, serum level of glutathione (GSH-PX/GR), duration of hospital and ICU stay. To evaluate the accuracy of calculated serum creatinine clearance (CSCC) in predicating the renal performance in OLT patients, another two serum markers will be estimated. The 1st one is Cystatin-C and the 2nd is Beta-trace. The data from CSCC, cystatin-C and beta-trace will be compared to find out which is the best marker in between these three tests to predicate the renal function. The data will be recorded daily for the first week after the surgery, then on days 14, 21, 30, 90, 180 and finely at the end of the first year after the OLT. Statistical analysis of the data will be performed at the conclusion of the study period to determine the difference in the outcome and morbidity and mortality between the two groups.
Objective and Specific Aims
Objectives:
- Assess the efficacy of NAC to preserve liver graft function and to improve patient/graft survival following orthotopic liver transplantation.
- Assess the efficacy of NAC to preserve kidney function in the patients undergoing OLT.
Primary Aims:
- Severity of the post reperfusion syndrome (PRS) will be compared in both groups by assessing hemodynamic parameters and the need for vasopressor support in the neohepatic stage.
- Liver graft function, the incidence of primary non-function and delayed function in both the treatment and placebo groups, will be assessed with post-operative liver function tests (ALT, AST, serum bilirubin, PT/INR, APTT, lactate, etc). Liver function tests will be assessed at one month, three month, six month and at one year following the OLT.
- The duration of ICU and hospital stays will be compared between the two groups.
- Survival rate (patient/graft) between the treatment and placebo groups will be compared at 1 month, 3 months, 6 months and 1 year.
- Renal function will be compared in the treatment and placebo groups by assessing the following parameters during and after liver transplantation: urine output (ml/24 hours), serum creatinine and BUN, calculated creatinine clearance.
- The incidence of postoperative acute renal failure (ARF) and the extent and duration of renal dysfunction will be compared between the treatment and the placebo groups.
Secondary Aims:
- Investigating the effect of NAC on the endogenous glutathione peroxides/glutathione reductase (GSH-PX/GR) body stores in patients undergoing OLT.
- Investigating the effect of NAC on FK506 induced toxicity.
- Investigating the accuracy of two new markers for evaluating the renal function and glomerular filtration rate and compare them to CSCC.
- Conditions
- End Stage Liver Failure
- Being tested
- N-acetylcysteine
- Keywords
- ARF, OLT, NAC, I/R injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetylcysteineDrug
Also called NAC, GSH, cystatin-c, beta-trace
The patients in the NAC group will receive a loading dose of 140 mg/kg IV of NAC over one hour at the start of the surgery. Thereafter, NAC will be repeated every 4 hours at a dose of 70 mg/kg IV, for a total of 13 doses
| Study group | Role | What they receive |
|---|---|---|
| 2 | Experimental | Not described Receives: Drug: N-acetylcysteine |
What is being measured
The primary outcome is the main question the study is designed to answer.
improve patient and graft outcome. reduce the incidence of postoperative renal dysfunction
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2008 (estimated)
- Study startJul 2004
- Primary completionApr 2007
- Study completionJan 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for End Stage Liver FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ibtesam Hilmi
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Ibtesam Hilmi, University of Pittsburgh
- Investigators
- Ibtesam A Hilmi, MB CHB, FRCA, Principal investigator, University of Pittsburgh Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00736541
- Sponsor's protocol ID
- N-acetylcysteine in OLT
- Acronym
- NAC
- Status last verified
- Apr 2023
- First submitted
- 14 Aug 2008
- Last updated
- 28 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of the Efficacy of N-acetylcysteine (NAC) to Protect Against Hepato-renal Ischemia-reperfusion Injury in Patients Undergoing Orthotopic Liver Transplantation
- ClinicalTrials.gov ID
- NCT00736541
- Acronym / sponsor ID
- NAC / N-acetylcysteine in OLT
- Conditions
- End Stage Liver Failure
- Keywords
- ARF, OLT, NAC, I/R injury
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Ibtesam HilmiUniversity, hospital or other
- Study start
- Jul 2004
- Primary completion
- Apr 2007 (actual)
- Study completion
- Jan 2008 (actual)
- First posted
- 18 Aug 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
N-acetylcysteine (NAC) is used to treat Tylenol toxicity. NAC is a rich source of the sulfhydryl group (SH) which is important for replenishing the body's glutathione stores. Glutathione acts as a free radical scavenger, to decrease the damage that would be caused by those toxic radicals. Patients who undergo orthotopic liver transplantation (OLT) have a high incidence of post-operative renal dysfunction. The most common etiology of post-operative renal dysfunction is related to high levels of toxic free radicals. Free radicals may contribute to primary liver graft failure or delayed liver graft function.
Specific Aims \& Objectives:
The primary objective of this study is to evaluate the efficacy of NAC in improving liver graft performance and lowering the incidence of post-operative renal dysfunction. The secondary objectives are to investigate the effect of NAC on endogenous glutathione body stores and its effect on FK506 induced toxicity.
Detailed description
This is a randomized, double-blind placebo-controlled study that investigates the use of NAC during and after OLT. A total of 100 patients will be recruited. Fifty will receive a placebo (normal saline) and the other fifty will receive NAC. The patients in the NAC group will receive a loading dose of 140 mg/kg IV of NAC over one hour at the start of the surgery. Thereafter, NAC will be repeated every 4 hours at a dose of 70 mg/kg IV, for a total of 13 doses. The placebo group will receive an equal volume of a normal saline infusion for 13 doses. Both groups will be followed for one year after their OLT. The following data will be recorded and collected: liver function tests, renal function tests, liver graft survival rate, patient survival, serum level of glutathione (GSH-PX/GR), duration of hospital and ICU stay. To evaluate the accuracy of calculated serum creatinine clearance (CSCC) in predicating the renal performance in OLT patients, another two serum markers will be estimated. The 1st one is Cystatin-C and the 2nd is Beta-trace. The data from CSCC, cystatin-C and beta-trace will be compared to find out which is the best marker in between these three tests to predicate the renal function. The data will be recorded daily for the first week after the surgery, then on days 14, 21, 30, 90, 180 and finely at the end of the first year after the OLT. Statistical analysis of the data will be performed at the conclusion of the study period to determine the difference in the outcome and morbidity and mortality between the two groups.
Objective and Specific Aims
Objectives:
- Assess the efficacy of NAC to preserve liver graft function and to improve patient/graft survival following orthotopic liver transplantation.
- Assess the efficacy of NAC to preserve kidney function in the patients undergoing OLT.
Primary Aims:
- Severity of the post reperfusion syndrome (PRS) will be compared in both groups by assessing hemodynamic parameters and the need for vasopressor support in the neohepatic stage.
- Liver graft function, the incidence of primary non-function and delayed function in both the treatment and placebo groups, will be assessed with post-operative liver function tests (ALT, AST, serum bilirubin, PT/INR, APTT, lactate, etc). Liver function tests will be assessed at one month, three month, six month and at one year following the OLT.
- The duration of ICU and hospital stays will be compared between the two groups.
- Survival rate (patient/graft) between the treatment and placebo groups will be compared at 1 month, 3 months, 6 months and 1 year.
- Renal function will be compared in the treatment and placebo groups by assessing the following parameters during and after liver transplantation: urine output (ml/24 hours), serum creatinine and BUN, calculated creatinine clearance.
- The incidence of postoperative acute renal failure (ARF) and the extent and duration of renal dysfunction will be compared between the treatment and the placebo groups.
Secondary Aims:
- Investigating the effect of NAC on the endogenous glutathione peroxides/glutathione reductase (GSH-PX/GR) body stores in patients undergoing OLT.
- Investigating the effect of NAC on FK506 induced toxicity.
- Investigating the accuracy of two new markers for evaluating the renal function and glomerular filtration rate and compare them to CSCC.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 2 | Experimental | Drug: N-acetylcysteine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male or female patients age of 18 years
- Patients undergoing cadaveric liver transplant for the first time
- Patients with normal serum creatinine < 1- 1.2 mg/dl or creatinine clearance 97-140 ml/min and patients with mild renal dysfunction with serum creatinine of (2-2.5 mg/dl) or creatinine clearance 85-125 ml/min
- All patients will sign informed consent
Key exclusion criteria (7 listed)
- Allergy to NAC
- Patients with history of asthma
- Patient with fulminate hepatic failure
- Re-do OLT
- Simultaneous other organ transplant (i.e., pancreas, heart, and small bowel)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-acetylcysteineAlso: NAC, GSH, cystatin-c, beta-traceThe patients in the NAC group will receive a loading dose of 140 mg/kg IV of NAC over one hour at the start of the surgery. Thereafter, NAC will be repeated every 4 hours at a dose of 70 mg/kg IV, for a total of 13 doses | Drug | 2 |
Primary outcome
improve patient and graft outcome. reduce the incidence of postoperative renal dysfunction
Time frame: one year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ibtesam A Hilmi, MB CHB, FRCA principal investigator
University of Pittsburgh Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing N-acetylcysteine in people with End Stage Liver Failure, run by Ibtesam Hilmi at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
improve patient and graft outcome. reduce the incidence of postoperative renal dysfunction (time frame: one year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2023.