Surgery--ComplicationsPhase 4NCT03440268
Prevention of Acute Kidney Injury by N-Acetylcystein in Patients Undergone Cardiac Valve Replacement
A Phase 4 study testing N Acetyl Cysteine in people with Surgery--Complications and Cardiac Valve Disease, run by University of Sao Paulo General Hospital at 1 site in Brazil.
Trial summary
This is a randomized clinical trial, double-blind, placebo-controlled study with the goal to assess the influence of using N-AcetylCysteyn (NAC) for prevention of AKI (Acute Kidney Injury) in post operatory of valve replacement until their discharge or death Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Surgery--Complications, Cardiac Valve Disease, Acute Kidney Injury
- What is being tested?
- N Acetyl Cysteine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 154 participants
- Where
- 1 siteBrazil
- Study dates
- 15 Mar 2018to 15 Mar 2020
- Phase
- Phase 4
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Adults
- Both sex
- Elective replacement valve (mitral or aortic) procedure
Who cannot join
- Chronic dialysis patients
- Emergency procedures
- Percutaneous procedures
- Pregnants
- Oncologic patients
Trial locations and contacts
1 site in 1 country.
Brazil1 site
José Jayme Galvão de Lima
São Paulo, 05403-900
José Jayme G de Lima, M.D, 1126615334, jose.lima@incor.usp.br
Felipe Kenji O Kamei, Specialist, 11997464073, fkok92@gmail.com
About this study
This is a randomized clinical trial, double-blind, placebo-controlled study with the goal to assess the influence of using N-AcetylCysteyn (NAC) for prevention of AKI (Acute Kidney Injury) in post operatory of valve replacement until their discharge or death
Read the detailed description
Acute kidney injury (AKI) is a serious complication after cardiovascular surgery. Pharmacologic interventions to prevent postoperative AKI have been, in general, unsuccessful. N-Acetylcystein (NAC) is a scavenger of reactive oxygen species that prevents renal dysfunction caused by radiocontrast agents but its ability to prevent AKI in cardiovascular surgery remains controversial. Lack of dose standardization and route of administration contributes to conflicting results in the literature. ln a earlier prospective, double-blind, placebo-controlled study 1 the investigators showed that high-dose NAC reduced the incidence of AKI in patients undergoing coronary artery bypass graft surgery. In this research the investigators aim to validate the results of the abovementioned work in a larger group of patients undergoing cardiac valve replacement, using the same protocol. Methods: This will be a unicentric, prospective, double-blind, placebo-controlled investigation. The Institutional Review Board has already approved the study protocol and all participants will sign a written informed consent. Adult patients of both sex scheduled to undergo elective cardiac valve replacement (aortic and/or mitral) at the Heart Institute, University of São Paulo Medical School, will be considered for inclusion. Exclusion criteria: patients younger than 18 years, dialysis, and participation in other studies, allergy to NAC, active infection, emergency cardiac surgery and malignancies. One-hundred fifty-four patients will be randomly allocated (1:1 ratio) to receive either NAC (Fluimucil, Zambon Laboratories, São Paulo, Brazil) 150 mg/kg in 500 mL 0.9% IV saline in 2 hours, started 2 hours before surgery, followed by NAC 50 mg/kg in 500 mL 0.9% IV saline over 6 hours (NAC group) or 0.9% IV saline (control group) at the same volume. This dose was selected because it is the highest dose sanctioned for clinical use 2 and because it has been shown to reduce the oxidative burst response to Cardiopulmonary Bypass (CPB). Allocation will be based on random computer generated numbers. Patients and investigators will be blinded to treatment assignment. Blood samples will be collected 24 hours before surgery and up to 1 week postoperatively. Serum neutrophil gelatinase associated lipocalin (NGAL) and thiobarbituric acid reactive substances will be determined at the same intervals.2 The primary outcome is the incidence of AKI, as defined by the KDIGO and Acute Kidney Injury Network classification 3 , stages 1, 2, or 3, in the first 72 hours after surgery. The secondary outcomes are death by any cause, cardiovascular events (myocardial infarction, stroke, heart failure, and life-threatening arrhythmia), time in the intensive care unit, time of hospitalization and need of dialysis. The investigators will determine thiobarbituric acid reactive substances to verify if changes in renal function would coincide with changes in oxidative stress and NGAL as an additional marker of renal damage. Patients will be followed up until death or hospital discharge. The renoprotective effect of NAC is attributed to its ability to attenuate the oxidative stress burst associated with cardiac surgery and Cardiopulmonary BYPASS (CPB). The present investigation pretend not only to address this problem, but also to offer evidence that NAC abolishes the increase in circulating reactive oxygen species thus giving a plausible explanation for the renoprotective effect of NAC. Given the clinical relevance of AKI associated to cardiac surgery, lack of dependable methods to prevent that complication and the reduced number of prospective, randomized studies addressing the problem, this work has potential practical relevance.
- Conditions
- Surgery--Complications, Cardiac Valve Disease, Acute Kidney Injury, Oxygen Radical Damage, Post-Op Complication
- Being tested
- N Acetyl Cysteine, Placebos
- Keywords
- cardiac surgery, post operatory complications, Acute kidney injury, N-acetylcystein
- Medical subject headings
- Heart Valve Diseases, Acute Kidney Injury, Postoperative Complications
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N Acetyl CysteineDrug
Also called NAC, experimental
Administrate NAC in the pre operatory and intra operatory moments and assess the influence in the outcomes
PlacebosDrug
Also called control
These participants will receive a saline solution in pre operatory with the same volume as the experimental group, and this solution will be administrated in 2 hours. During the surgery they will receive a new solution with the same volume of the experimental group, and this solution will be administrated in 6 hours too. The solutions will be covered by an opaque bag, so the participant will not see what is being administrated
| Study group | Role | What they receive |
|---|---|---|
| N Acetyl Cysteine | Experimental | NAC in pre operatory 150mg/kg infusion in 2 hours. NAC during the surgery 50mg/kg in 6 hours. The influence of NAC will be assess in post operatory moment with routine exams Receives: Drug: N Acetyl Cysteine |
| Placebos | Placebo comparator | Saline solution in pre operatory. Saline Solution duing the surgery. The post operatory datas of both groups will be compare Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
NAC and acute kidney injury (AKI)
Assess the influence of using NAC in the incidence of AKI by using the Kidney diagnosis improving outcomes (KDIGO) score and Acute kidney injury network (AKIN) score that use the creatinine seric and urine output values to define if we can or not diagnosis acute kidney injury in this pacient. The incidence of AKI will be defined by KDIGO criterea: AKI if creatinine raises up to 1,5 times the baseline, until 7 days. Or if seric creatinine raises 0,3mg/dL up to baseline in 48 hours. Urine output: less than 0,5ml/kg/h for 6-12 hours AKIN criterea: AKI if creatinine raises up to 1,5 times the baseline, until 7 days. Or if seric creatinine raises 0,3mg/dL up to baseline in 48 hours. Urine output: less than 0,5ml/kg/h for 6-12 hours
Measured: The participants will be assess in the day before the surgery (baseline), and daily until 7 days of post operatory
Secondary outcomes (2)
NAC and kidney replacement therapy (KRT)
Assess the influence of using NAC in the incidence of the necessity of KRT.
Measured: From the post operatory until the necessity of KRT, assessed up 2 months
NAC and death
Assess the influence of using NAC in the incidence of death
Measured: From the post operatory until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2018
- Study start15 Mar 2018 (estimated)
- Primary completion15 Mar 2019 (estimated)
- Study completion15 Mar 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Surgery--ComplicationsStudies of the same condition, open and under way.
- More trials run by University of Sao Paulo General HospitalThe 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- There will be one group placebo/control and one group intervention. The group intervention will receive the medication N AcetylCysteyn (NAC), while the control will receive a placebo
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 154 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jose Jayme Galvão de Lima, University of Sao Paulo General Hospital
- Investigators
- José J Galvão de Lima, PhD, Principal investigator, USP InCor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03440268
- Sponsor's protocol ID
- NAC Valve
- Status last verified
- Mar 2018
- First submitted
- 5 Jan 2018
- Last updated
- 5 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: We don't have fixed reviewers for our data until our submission for publication
Publications
Spector A. Review: Oxidative stress and disease. J Ocul Pharmacol Ther. 2000 Apr;16(2):193-201. doi: 10.1089/jop.2000.16.193.
PubMed 10803430Suen WS, Mok CK, Chiu SW, Cheung KL, Lee WT, Cheung D, Das SR, He GW. Risk factors for development of acute renal failure (ARF) requiring dialysis in patients undergoing cardiac surgery. Angiology. 1998 Oct;49(10):789-800. doi: 10.1177/000331979804900902.
PubMed 9783643Bahar I, Akgul A, Ozatik MA, Vural KM, Demirbag AE, Boran M, Tasdemir O. Acute renal failure following open heart surgery: risk factors and prognosis. Perfusion. 2005 Oct;20(6):317-22. doi: 10.1191/0267659105pf829oa.
PubMed 16363316
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Acute Kidney Injury by N-Acetylcystein in Patients Undergone Cardiac Valve Replacement
- ClinicalTrials.gov ID
- NCT03440268
- Acronym / sponsor ID
- NAC Valve
- Conditions
- Surgery--Complications, Cardiac Valve Disease, Acute Kidney Injury, Oxygen Radical Damage, Post-Op Complication
- Keywords
- cardiac surgery, post operatory complications, Acute kidney injury, N-acetylcystein
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 154 participants (estimated)
- Lead sponsor
- University of Sao Paulo General HospitalUniversity, hospital or other
- Study start
- 15 Mar 2018 (estimated)
- Primary completion
- 15 Mar 2019 (estimated)
- Study completion
- 15 Mar 2020 (estimated)
- First posted
- 22 Feb 2018 (actual)
- 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.
This is a randomized clinical trial, double-blind, placebo-controlled study with the goal to assess the influence of using N-AcetylCysteyn (NAC) for prevention of AKI (Acute Kidney Injury) in post operatory of valve replacement until their discharge or death
Detailed description
Acute kidney injury (AKI) is a serious complication after cardiovascular surgery. Pharmacologic interventions to prevent postoperative AKI have been, in general, unsuccessful. N-Acetylcystein (NAC) is a scavenger of reactive oxygen species that prevents renal dysfunction caused by radiocontrast agents but its ability to prevent AKI in cardiovascular surgery remains controversial. Lack of dose standardization and route of administration contributes to conflicting results in the literature. ln a earlier prospective, double-blind, placebo-controlled study 1 the investigators showed that high-dose NAC reduced the incidence of AKI in patients undergoing coronary artery bypass graft surgery. In this research the investigators aim to validate the results of the abovementioned work in a larger group of patients undergoing cardiac valve replacement, using the same protocol. Methods: This will be a unicentric, prospective, double-blind, placebo-controlled investigation. The Institutional Review Board has already approved the study protocol and all participants will sign a written informed consent. Adult patients of both sex scheduled to undergo elective cardiac valve replacement (aortic and/or mitral) at the Heart Institute, University of São Paulo Medical School, will be considered for inclusion. Exclusion criteria: patients younger than 18 years, dialysis, and participation in other studies, allergy to NAC, active infection, emergency cardiac surgery and malignancies. One-hundred fifty-four patients will be randomly allocated (1:1 ratio) to receive either NAC (Fluimucil, Zambon Laboratories, São Paulo, Brazil) 150 mg/kg in 500 mL 0.9% IV saline in 2 hours, started 2 hours before surgery, followed by NAC 50 mg/kg in 500 mL 0.9% IV saline over 6 hours (NAC group) or 0.9% IV saline (control group) at the same volume. This dose was selected because it is the highest dose sanctioned for clinical use 2 and because it has been shown to reduce the oxidative burst response to Cardiopulmonary Bypass (CPB). Allocation will be based on random computer generated numbers. Patients and investigators will be blinded to treatment assignment. Blood samples will be collected 24 hours before surgery and up to 1 week postoperatively. Serum neutrophil gelatinase associated lipocalin (NGAL) and thiobarbituric acid reactive substances will be determined at the same intervals.2 The primary outcome is the incidence of AKI, as defined by the KDIGO and Acute Kidney Injury Network classification 3 , stages 1, 2, or 3, in the first 72 hours after surgery. The secondary outcomes are death by any cause, cardiovascular events (myocardial infarction, stroke, heart failure, and life-threatening arrhythmia), time in the intensive care unit, time of hospitalization and need of dialysis. The investigators will determine thiobarbituric acid reactive substances to verify if changes in renal function would coincide with changes in oxidative stress and NGAL as an additional marker of renal damage. Patients will be followed up until death or hospital discharge. The renoprotective effect of NAC is attributed to its ability to attenuate the oxidative stress burst associated with cardiac surgery and Cardiopulmonary BYPASS (CPB). The present investigation pretend not only to address this problem, but also to offer evidence that NAC abolishes the increase in circulating reactive oxygen species thus giving a plausible explanation for the renoprotective effect of NAC. Given the clinical relevance of AKI associated to cardiac surgery, lack of dependable methods to prevent that complication and the reduced number of prospective, randomized studies addressing the problem, this work has potential practical relevance.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- There will be one group placebo/control and one group intervention. The group intervention will receive the medication N AcetylCysteyn (NAC), while the control will receive a placebo
| Arm | Type | Receives |
|---|---|---|
| N Acetyl Cysteine | Experimental | Drug: N Acetyl CysteineNAC in pre operatory 150mg/kg infusion in 2 hours. NAC during the surgery 50mg/kg in 6 hours. The influence of NAC will be assess in post operatory moment with routine exams |
| Placebos | Placebo comparator | Drug: PlacebosSaline solution in pre operatory. Saline Solution duing the surgery. The post operatory datas of both groups will be compare |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Adults
- Both sex
- Elective replacement valve (mitral or aortic) procedure
Key exclusion criteria (5 listed)
- Chronic dialysis patients
- Emergency procedures
- Percutaneous procedures
- Pregnants
- Oncologic patients
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 Acetyl CysteineAlso: NAC, experimentalAdministrate NAC in the pre operatory and intra operatory moments and assess the influence in the outcomes | Drug | N Acetyl Cysteine |
| PlacebosAlso: controlThese participants will receive a saline solution in pre operatory with the same volume as the experimental group, and this solution will be administrated in 2 hours. During the surgery they will receive a new solution with the same volume of the experimental group, and this solution will be administrated in 6 hours too. The solutions will be covered by an opaque bag, so the participant will not see what is being administrated | Drug | Placebos |
Primary outcome
NAC and acute kidney injury (AKI)
Time frame: The participants will be assess in the day before the surgery (baseline), and daily until 7 days of post operatory
Assess the influence of using NAC in the incidence of AKI by using the Kidney diagnosis improving outcomes (KDIGO) score and Acute kidney injury network (AKIN) score that use the creatinine seric and urine output values to define if we can or not diagnosis acute kidney injury in this pacient. The incidence of AKI will be defined by KDIGO criterea: AKI if creatinine raises up to 1,5 times the baseline, until 7 days. Or if seric creatinine raises 0,3mg/dL up to baseline in 48 hours. Urine output: less than 0,5ml/kg/h for 6-12 hours AKIN criterea: AKI if creatinine raises up to 1,5 times the baseline, until 7 days. Or if seric creatinine raises 0,3mg/dL up to baseline in 48 hours. Urine output: less than 0,5ml/kg/h for 6-12 hours
2 secondary outcomes
NAC and kidney replacement therapy (KRT)
Time frame: From the post operatory until the necessity of KRT, assessed up 2 months
NAC and death
Time frame: From the post operatory until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2018.
- Background: PubMed 10803430Spector A. Review: Oxidative stress and disease. J Ocul Pharmacol Ther. 2000 Apr;16(2):193-201. doi: 10.1089/jop.2000.16.193.
- Results publication: PubMed 9783643Suen WS, Mok CK, Chiu SW, Cheung KL, Lee WT, Cheung D, Das SR, He GW. Risk factors for development of acute renal failure (ARF) requiring dialysis in patients undergoing cardiac surgery. Angiology. 1998 Oct;49(10):789-800. doi: 10.1177/000331979804900902.
- Results publication: PubMed 16363316Bahar I, Akgul A, Ozatik MA, Vural KM, Demirbag AE, Boran M, Tasdemir O. Acute renal failure following open heart surgery: risk factors and prognosis. Perfusion. 2005 Oct;20(6):317-22. doi: 10.1191/0267659105pf829oa.
- Individual participant dataSharing planned: No. We don't have fixed reviewers for our data until our submission for publication
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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.
José J Galvão de Lima, PhD principal investigator
USP InCor
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing N Acetyl Cysteine in people with Surgery--Complications and Cardiac Valve Disease, run by University of Sao Paulo General Hospital at 1 site in Brazil.
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 3 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 5 Mar 2018. 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 Brazil. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact José J Galvão de Lima, PhD (1126615334 ext. +55, jose.lima@incor.usp.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
NAC and acute kidney injury (AKI) (time frame: The participants will be assess in the day before the surgery (baseline), and daily until 7 days of post operatory). 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 NCT03440268, which also lists 3 linked publications.
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 5 Mar 2018.