Heart DiseasePhase 3NCT00188630
N-Acetylcysteine for Preventing Renal Injury After Cardiac Surgery
A Phase 3 study testing N-acetylcysteine and 5% dextrose solution in people with Heart Disease and Acute Renal Failure, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
Cardiac surgery improves the survival and quality of life of people with heart disease. Nonetheless, several complications continue to adversely affect outcomes following cardiac surgery. Kidney failure is a particularly important complication that is associated with increased death and duration of hospitalization. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Disease, Acute Renal Failure
- What is being tested?
- N-acetylcysteine and 5% dextrose solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 176 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2003to Jul 2007
- Phase
- Phase 3
- 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
- CABG surgery under cardiopulmonary bypass AND/OR Valve replacement/repair surgery under cardiopulmonary bypass
- Preoperative creatinine clearance (Cockcroft-Gault equation) <= 60 mL/min.
- Age above 18 years
- Informed consent
Who cannot join
- Preoperative need for renal replacement therapy
- Preoperative serum creatinine concentration >= 300 mmol/L
- Prior adverse reaction to NAC with significant systemic symptoms (generalized rash, urticaria, bronchospasm, hypotension)
- Preoperative intra-aortic balloon pump support and/or inotropes/vasopressors
- Recent coronary angiography or intravenous dye exposure (<= 24 hours) preceding surgery
- Planned intraoperative deep hypothermic circulatory arrest
- Pregnancy
- Chronic hepatitis or hepatic cirrhosis
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The PRIME (Perioperative Renal Insufficiency Management) Study: A Randomized, Double-blinded, Placebo-controlled Trial of N-acetylcysteine for Preventing Renal Injury After Cardiac Surgery.
Cardiac surgery improves the survival and quality of life of people with heart disease. Nonetheless, several complications continue to adversely affect outcomes following cardiac surgery. Kidney failure is a particularly important complication that is associated with increased death and duration of hospitalization. The most severe form of postoperative kidney failure, the need for dialysis, is uncommon at present. It is however likely to increase in the future. Patients undergoing cardiac surgery are getting older with more heart failure, diabetes, high blood pressure, and pre-existing kidney disease. Given that these are risk factors for postoperative kidney injury, dialysis rates will likely increase. Although multiple therapies have been tested, none have prevented postoperative kidney failure. N-acetylcysteine (NAC) is a drug that is commonly used to treat Tylenol overdoses. Over the past 2 years, it has also been used to prevent kidney damage after exposure to IV dye. There is good evidence that NAC will reduce kidney damage after IV dye exposure. There are strong reasons to believe that NAC may also prevent postoperative kidney failure. NAC is safe. Its major side-effects are allergic reactions, but serious reactions are rare. Since dialysis is uncommon, large studies are needed to determine if NAC prevents postoperative dialysis. In this situation, a pilot study is needed to determine if such a large trial is feasible. This proposal describes a pilot study. We will determine NAC's effects on creatinine clearance, a measure of how well the kidney works. Reduced creatinine clearance is closely related to dialysis and death after cardiac surgery. This biological marker allows us to determine NAC's effects on kidney function with a reduced sample size. If NAC improves creatinine clearance, it would suggest that NAC prevents postoperative dialysis, and would justify a larger study. A pilot study will help us estimate how many patients will be willing to participate in similar studies, vital for planning a future large study. Finally, our results will estimate how well NAC will reduce dialysis rates. This is needed for calculating the sample size for future studies.The study design is a randomized, double-blinded, placebo-controlled clinical trial among patients undergoing bypass surgery or heart valve surgery at the Toronto General Hospital (Toronto, ON). We will recruit 176 people who are at increased risk for developing kidney failure after surgery. Participants will receive either NAC or sugar solution during their operation. If participants have returned home within a month of surgery, they will be contacted at home on the 30th day after surgery to determine if they had any kidney-related problems since returning home. All participants will return to the Toronto General Hospital (TGH) during the 8th week after surgery for creatinine blood test and weight.
- Conditions
- Heart Disease, Acute Renal Failure
- Being tested
- N-acetylcysteine, 5% dextrose solution
- Keywords
- Cardiac Surgery, Acute Renal Failure, N-acetylcysteine, Cardiopulmonary bypass
- Medical subject headings
- Heart Diseases, Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetylcysteineDrug
5% dextrose solutionOther
| Study group | Role | What they receive |
|---|---|---|
| N-Acetylcysteine | Active comparator | IV NAC as a 100mg/kg bolus at the start of the surgical procedure (prior to the initiation of CPB), followed by a 10 mg/kg/hr infusion until 4 hours after completion of surgery Receives: Drug: N-acetylcysteine |
| Placebo | Placebo comparator | The control arm will instead receive placebo (5% dextrose solution), both as a bolus and infusion. Receives: Other: 5% dextrose solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum percent decline in calculated creatinine clearance (Cockcroft-Gault formula) in first 72 hours following surgery.
Measured: 72 hours following surgery
Secondary outcomes (12)
Maximum increase in serum creatinine concentration over first 72 hours following surgery.
Measured: 72 hours following surgery
Increase in serum creatinine >= 0.5 mg/dL from baseline over first 72 hours following surgery (dichotomous outcome).
Measured: 72 hours following surgery
Maximum percent decline in calculated creatinine clearance (Cockcroft-Gault formula) >= 25% in first 72 hours following surgery (dichotomous outcome).
Measured: 72 hours following surgery
Percent change in calculated creatinine clearance (Cockcroft-Gault formula) at hospital discharge.
Measured: hospital discharge
Maximum percent decline in calculated creatinine clearance (Cockcroft-Gault formula) at 8 weeks following surgery.
Measured: 8 weeks followiing surgery
30-day need for renal replacement therapy
Measured: 30 day inclusive
30-day all-cause mortality
Measured: 30 day follow up
Length of stay in intensive care unit (postoperative)
Measured: Duration of stay in the ICU
Length of stay in hospital (postoperative)
Measured: Until discharge form hospital
24-hour fluid perioperative fluid balance
Measured: 24 hours
24-hour urine output
Measured: 24 hour
Adverse perioperative event
Measured: Intra operative measure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2005 (estimated)
- Study startJul 2003
- Primary completionFeb 2007
- Study completionJul 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart DiseaseStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 176 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Heart and Stroke Foundation of Ontario
- Investigators
- William S Beattie, MD, Principal investigator, Toronto General Hospital, University Health Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00188630
- Sponsor's protocol ID
- UHN REB 03-0376-B
- Other IDs
- HSFO5231
- Status last verified
- Apr 2011
- First submitted
- 9 Sep 2005
- Last updated
- 20 Apr 2011
- Results posted
- No
Publications
Wijeysundera DN, Karkouti K, Rao V, Granton JT, Chan CT, Raban R, Carroll J, Poonawala H, Beattie WS. N-acetylcysteine is associated with increased blood loss and blood product utilization during cardiac surgery. Crit Care Med. 2009 Jun;37(6):1929-34. doi: 10.1097/CCM.0b013e31819ffed4.
PubMed 19384218
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The PRIME (Perioperative Renal Insufficiency Management) Study: A Randomized, Double-blinded, Placebo-controlled Trial of N-acetylcysteine for Preventing Renal Injury After Cardiac Surgery.
- ClinicalTrials.gov ID
- NCT00188630
- Acronym / sponsor ID
- UHN REB 03-0376-B
- Conditions
- Heart Disease, Acute Renal Failure
- Keywords
- Cardiac Surgery, Acute Renal Failure, N-acetylcysteine, Cardiopulmonary bypass
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 176 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Heart and Stroke Foundation of Ontario
- Study start
- Jul 2003
- Primary completion
- Feb 2007 (actual)
- Study completion
- Jul 2007 (actual)
- First posted
- 16 Sep 2005 (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.
Cardiac surgery improves the survival and quality of life of people with heart disease. Nonetheless, several complications continue to adversely affect outcomes following cardiac surgery. Kidney failure is a particularly important complication that is associated with increased death and duration of hospitalization. The most severe form of postoperative kidney failure, the need for dialysis, is uncommon at present. It is however likely to increase in the future. Patients undergoing cardiac surgery are getting older with more heart failure, diabetes, high blood pressure, and pre-existing kidney disease. Given that these are risk factors for postoperative kidney injury, dialysis rates will likely increase. Although multiple therapies have been tested, none have prevented postoperative kidney failure. N-acetylcysteine (NAC) is a drug that is commonly used to treat Tylenol overdoses. Over the past 2 years, it has also been used to prevent kidney damage after exposure to IV dye. There is good evidence that NAC will reduce kidney damage after IV dye exposure. There are strong reasons to believe that NAC may also prevent postoperative kidney failure. NAC is safe. Its major side-effects are allergic reactions, but serious reactions are rare. Since dialysis is uncommon, large studies are needed to determine if NAC prevents postoperative dialysis. In this situation, a pilot study is needed to determine if such a large trial is feasible. This proposal describes a pilot study. We will determine NAC's effects on creatinine clearance, a measure of how well the kidney works. Reduced creatinine clearance is closely related to dialysis and death after cardiac surgery. This biological marker allows us to determine NAC's effects on kidney function with a reduced sample size. If NAC improves creatinine clearance, it would suggest that NAC prevents postoperative dialysis, and would justify a larger study. A pilot study will help us estimate how many patients will be willing to participate in similar studies, vital for planning a future large study. Finally, our results will estimate how well NAC will reduce dialysis rates. This is needed for calculating the sample size for future studies.The study design is a randomized, double-blinded, placebo-controlled clinical trial among patients undergoing bypass surgery or heart valve surgery at the Toronto General Hospital (Toronto, ON). We will recruit 176 people who are at increased risk for developing kidney failure after surgery. Participants will receive either NAC or sugar solution during their operation. If participants have returned home within a month of surgery, they will be contacted at home on the 30th day after surgery to determine if they had any kidney-related problems since returning home. All participants will return to the Toronto General Hospital (TGH) during the 8th week after surgery for creatinine blood test and weight.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| N-Acetylcysteine | Active comparator | Drug: N-acetylcysteineIV NAC as a 100mg/kg bolus at the start of the surgical procedure (prior to the initiation of CPB), followed by a 10 mg/kg/hr infusion until 4 hours after completion of surgery |
| Placebo | Placebo comparator | Other: 5% dextrose solutionThe control arm will instead receive placebo (5% dextrose solution), both as a bolus and infusion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- CABG surgery under cardiopulmonary bypass AND/OR Valve replacement/repair surgery under cardiopulmonary bypass
- Preoperative creatinine clearance (Cockcroft-Gault equation) <= 60 mL/min.
- Age above 18 years
- Informed consent
Key exclusion criteria (8 listed)
- Preoperative need for renal replacement therapy
- Preoperative serum creatinine concentration >= 300 mmol/L
- Prior adverse reaction to NAC with significant systemic symptoms (generalized rash, urticaria, bronchospasm, hypotension)
- Preoperative intra-aortic balloon pump support and/or inotropes/vasopressors
- Recent coronary angiography or intravenous dye exposure (<= 24 hours) preceding surgery
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-acetylcysteine | Drug | N-Acetylcysteine |
| 5% dextrose solution | Other | Placebo |
Primary outcome
Maximum percent decline in calculated creatinine clearance (Cockcroft-Gault formula) in first 72 hours following surgery.
Time frame: 72 hours following surgery
12 secondary outcomes
Maximum increase in serum creatinine concentration over first 72 hours following surgery.
Time frame: 72 hours following surgery
Increase in serum creatinine >= 0.5 mg/dL from baseline over first 72 hours following surgery (dichotomous outcome).
Time frame: 72 hours following surgery
Maximum percent decline in calculated creatinine clearance (Cockcroft-Gault formula) >= 25% in first 72 hours following surgery (dichotomous outcome).
Time frame: 72 hours following surgery
Percent change in calculated creatinine clearance (Cockcroft-Gault formula) at hospital discharge.
Time frame: hospital discharge
Maximum percent decline in calculated creatinine clearance (Cockcroft-Gault formula) at 8 weeks following surgery.
Time frame: 8 weeks followiing surgery
30-day need for renal replacement therapy
Time frame: 30 day inclusive
30-day all-cause mortality
Time frame: 30 day follow up
Length of stay in intensive care unit (postoperative)
Time frame: Duration of stay in the ICU
Length of stay in hospital (postoperative)
Time frame: Until discharge form hospital
24-hour fluid perioperative fluid balance
Time frame: 24 hours
24-hour urine output
Time frame: 24 hour
Adverse perioperative event
Time frame: Intra operative measure
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 20 Apr 2011.
- Derived from this study: PubMed 19384218Wijeysundera DN, Karkouti K, Rao V, Granton JT, Chan CT, Raban R, Carroll J, Poonawala H, Beattie WS. N-acetylcysteine is associated with increased blood loss and blood product utilization during cardiac surgery. Crit Care Med. 2009 Jun;37(6):1929-34. doi: 10.1097/CCM.0b013e31819ffed4.
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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.
William S Beattie, MD principal investigator
Toronto General Hospital, University Health Network
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing N-acetylcysteine and 5% dextrose solution in people with Heart Disease and Acute Renal Failure, run by University Health Network, Toronto at 1 site in Canada.
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 8 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 20 Apr 2011. 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 Canada. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Maximum percent decline in calculated creatinine clearance (Cockcroft-Gault formula) in first 72 hours following surgery. (time frame: 72 hours following surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00188630, which also lists 1 linked publication.
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 20 Apr 2011.