Acute Kidney InjuryPhase 3NCT03331146
Nitrite Infusion in High Risk Patients Undergoing Cardiopulmonary Bypass
A Phase 3 study testing Saline and Sodium Nitrite in people with Acute Kidney Injury, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
The main objective of this study is to evaluate the efficacy of intravenous sodium nitrite compared with placebo in reducing the occurrence of CSA-AK as diagnosed by KDIGO criteria during the first 72 hrs after cardiac surgery in high-risk patients undergoing cardiac surgery. Read more about this study
- Who is it for?
- Ages 19 to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- Acute Kidney Injury
- What is being tested?
- Saline and Sodium Nitrite
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2018to 1 Dec 2020
- 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 19 to 100 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients CCFS score ≥ 6 (Table 1)
- Patients admitted to UAB cardiac intensive care unit (CICU) following elective cardiac surgery with cardiopulmonary bypass under general endotracheal anesthesia
- 19 years old
- Estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73 m2
Who cannot join
- Prisoners directly admitted from a correctional facility.
- Children < 19 years or under 50 kg body weight if age is unknown.
- Patients enrolled in a concurrent ongoing interventional, randomized clinical trial.
- Patients with end stage renal disease or preexisting GFR <30 mL/min/1.73 m2 or need for dialysis. 34
- Patients with end stage heart disease on the cardiac transplant list.
- Patients undergoing procedures without the use of CPB
Show all 11Show fewer
- All transplant patients.
- Patients on ventricular assist devices.
- Patients undergoing emergency procedures.
- Patients with glucose 6-dehydrogenase deficiency
- Pregnancy
Trial locations and contacts
1 site in 1 country.
United States1 site
UAB Department of Anesthesiology and Perioperative Medicine
Birmingham, Alabama, 35249
About this study
Official title: Randomized, Controlled, Double-blinded Pilot Study: Nitrite Infusion in High Risk Patients Undergoing Cardiopulmonary Bypass
The main objective of this study is to evaluate the efficacy of intravenous sodium nitrite compared with placebo in reducing the occurrence of CSA-AK as diagnosed by KDIGO criteria during the first 72 hrs after cardiac surgery in high-risk patients undergoing cardiac surgery. Secondary objectives are to determine whether IV sodium nitrite achieves adequate pharmacokinetics (PK) in patients undergoing cardiac surgery with the use of CPB.
Read the detailed description
Acute kidney injury is one of the most untoward consequences of cardiac-surgery with the use of CPB. As such it is associated with a high mortality and morbidity and health care expense. Unfortunately, currently, there is no effective preventive or treatment strategy for cardiac surgery-associated (CSA) AKI other than renal replacement therapy.
It is postulated that a major mechanism of CSA-AKI is created by the ischemia reperfusion injury (IRI) resulting from aortic cross clamping and unclamping. This creates a cascade of events culminating in inflammation, microvascular dysfunction and tubular cell maladaptation and eventually renal tissue damage. Current treatment modalities that target the microcirculation such as blood pressure and cardiac output fails to prevent renal abnormalities and as such may be deleterious to the renal tissue microcirculation. The PI hypothesizes that a therapeutic strategy that limits IRI such as the administration of inhaled nitric oxide (NO) or sodium nitrite (NaNO2) would ameliorate CSA-AKI by limiting inflammatory injury to the kidney.
The anion nitrite (NO2-) releases NO in biological systems and has been demonstrated to inhibit IR injury in the heart, liver and kidneys created by various pathologic states1-3 and improve outcomes in patients with acute myocardial infarction, in patients with pulmonary hypertension and is the putative active mediator of protection in liver-transplantation patients receiving inhaled nitric oxide4.
The objective of this study is to determine whether the NO donor, nitrite will prevent I/R injury in patients at high risk of development of CSA-AKI undergoing open-heart surgery with cardiopulmonary bypass.
- Conditions
- Acute Kidney Injury
- Being tested
- Saline, Sodium Nitrite
- Keywords
- Nitric Oxide, Sodium Nitrite, Cardiopulmonary bypass, cardioplegic cardiac arrest, coronary revacularization
- Medical subject headings
- Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SalineDrug
A placebo (saline infusion) will be administered after induction of general anesthesia.
Sodium NitriteDrug
Also called NaNO2
Sodium nitrite infusion at a 267 mcg/kg/hr. will start after induction of general anesthesia via a dedicated IV line for 6 hrs.
| Study group | Role | What they receive |
|---|---|---|
| Control group | Placebo comparator | saline infusion will be administered after induction of general anesthesia Receives: Drug: Saline; Drug: Sodium Nitrite |
| Sodium Nitrite | Active comparator | sodium nitrite will start after induction of general anesthesia via a dedicated IV line for 6 hrs. Receives: Drug: Saline; Drug: Sodium Nitrite |
What is being measured
The primary outcome is the main question the study is designed to answer.
Nitrite Metabolome Levels
Measuring nitrite, nitrate, and nitrosothiols levels
Measured: baseline to 73 hrs post-operatively
Biomarkers of Hemolysis
Measuring hemolysis indicators heme, Hb, hemopexin, and hemopectin
Measured: baseline to 73 hrs post-operatively
Biomarkers of Kidney Injury
Measuring kidney injury indicators creatine, neutrophil-associated gelatinase, lipocalin (NGAL)
Measured: baseline to 73 hrs post-operatively
Cell Cycle Stress
Measuring cell cycle arrest biomarkers TIMP-2, IGFBP-7
Measured: baseline to 73 hrs post-operatively
Secondary outcomes (6)
Biomarkers of Hepatic injury
Measuring serum AST and ALT
Measured: baseline to 24 hours post-operatively
Biomarkers of Kidney Injury
Measuring kidney injury indicators creatine, neutrophil, lipocalin (NGAL)
Measured: baseline to 24 hours post-operatively
Cell Cycle Stress
Measuring cell cycle arrest biomarkers TIMP-2, IGFBP-7
Measured: baseline to 24 hours post-operatively
Biomarkers of Myocardial Injury
Measuring myocardial injury indicators troponin and CKMB
Measured: baseline to 24 hours post-operatively
Urine Output
Measuring total urine output
Measured: baseline to 73 hrs post-operatively
Vasopressors Usage
Percentage of vasopressor usage between the control and intervention
Measured: baseline to 73 hrs post-operatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2017
- Study start1 Oct 2018 (estimated)
- Primary completion1 Jun 2019 (estimated)
- Study completion1 Dec 2020 (estimated)
Why it stopped: Principal Investigator made aware of similar studies that have already been published.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Kidney InjuryStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ahmed Zaky, University of Alabama at Birmingham
- Investigators
- Ahmed F Zaky, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03331146
- Sponsor's protocol ID
- 1709284471
- Status last verified
- Sep 2018
- First submitted
- 20 Oct 2017
- Last updated
- 27 Sep 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Controlled, Double-blinded Pilot Study: Nitrite Infusion in High Risk Patients Undergoing Cardiopulmonary Bypass
- ClinicalTrials.gov ID
- NCT03331146
- Acronym / sponsor ID
- 1709284471
- Conditions
- Acute Kidney Injury
- Keywords
- Nitric Oxide, Sodium Nitrite, Cardiopulmonary bypass, cardioplegic cardiac arrest, coronary revacularization
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Principal Investigator made aware of similar studies that have already been published.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- 1 Oct 2018 (estimated)
- Primary completion
- 1 Jun 2019 (estimated)
- Study completion
- 1 Dec 2020 (estimated)
- First posted
- 6 Nov 2017 (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.
The main objective of this study is to evaluate the efficacy of intravenous sodium nitrite compared with placebo in reducing the occurrence of CSA-AK as diagnosed by KDIGO criteria during the first 72 hrs after cardiac surgery in high-risk patients undergoing cardiac surgery. Secondary objectives are to determine whether IV sodium nitrite achieves adequate pharmacokinetics (PK) in patients undergoing cardiac surgery with the use of CPB.
Detailed description
Acute kidney injury is one of the most untoward consequences of cardiac-surgery with the use of CPB. As such it is associated with a high mortality and morbidity and health care expense. Unfortunately, currently, there is no effective preventive or treatment strategy for cardiac surgery-associated (CSA) AKI other than renal replacement therapy.
It is postulated that a major mechanism of CSA-AKI is created by the ischemia reperfusion injury (IRI) resulting from aortic cross clamping and unclamping. This creates a cascade of events culminating in inflammation, microvascular dysfunction and tubular cell maladaptation and eventually renal tissue damage. Current treatment modalities that target the microcirculation such as blood pressure and cardiac output fails to prevent renal abnormalities and as such may be deleterious to the renal tissue microcirculation. The PI hypothesizes that a therapeutic strategy that limits IRI such as the administration of inhaled nitric oxide (NO) or sodium nitrite (NaNO2) would ameliorate CSA-AKI by limiting inflammatory injury to the kidney.
The anion nitrite (NO2-) releases NO in biological systems and has been demonstrated to inhibit IR injury in the heart, liver and kidneys created by various pathologic states1-3 and improve outcomes in patients with acute myocardial infarction, in patients with pulmonary hypertension and is the putative active mediator of protection in liver-transplantation patients receiving inhaled nitric oxide4.
The objective of this study is to determine whether the NO donor, nitrite will prevent I/R injury in patients at high risk of development of CSA-AKI undergoing open-heart surgery with cardiopulmonary bypass.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control group | Placebo comparator | Drug: Saline, Drug: Sodium Nitritesaline infusion will be administered after induction of general anesthesia |
| Sodium Nitrite | Active comparator | Drug: Saline, Drug: Sodium Nitritesodium nitrite will start after induction of general anesthesia via a dedicated IV line for 6 hrs. |
Who may qualify
- Ages
- 19 to 100 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients CCFS score ≥ 6 (Table 1)
- Patients admitted to UAB cardiac intensive care unit (CICU) following elective cardiac surgery with cardiopulmonary bypass under general endotracheal anesthesia
- 19 years old
- Estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73 m2
Key exclusion criteria (11 listed)
- Prisoners directly admitted from a correctional facility.
- Children < 19 years or under 50 kg body weight if age is unknown.
- Patients enrolled in a concurrent ongoing interventional, randomized clinical trial.
- Patients with end stage renal disease or preexisting GFR <30 mL/min/1.73 m2 or need for dialysis. 34
- Patients with end stage heart disease on the cardiac transplant list.
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 |
|---|---|---|
| SalineA placebo (saline infusion) will be administered after induction of general anesthesia. | Drug | Control group, Sodium Nitrite |
| Sodium NitriteAlso: NaNO2Sodium nitrite infusion at a 267 mcg/kg/hr. will start after induction of general anesthesia via a dedicated IV line for 6 hrs. | Drug | Control group, Sodium Nitrite |
Primary outcome
Nitrite Metabolome Levels
Time frame: baseline to 73 hrs post-operatively
Measuring nitrite, nitrate, and nitrosothiols levels
Biomarkers of Hemolysis
Time frame: baseline to 73 hrs post-operatively
Measuring hemolysis indicators heme, Hb, hemopexin, and hemopectin
Biomarkers of Kidney Injury
Time frame: baseline to 73 hrs post-operatively
Measuring kidney injury indicators creatine, neutrophil-associated gelatinase, lipocalin (NGAL)
Cell Cycle Stress
Time frame: baseline to 73 hrs post-operatively
Measuring cell cycle arrest biomarkers TIMP-2, IGFBP-7
6 secondary outcomes
Biomarkers of Hepatic injury
Time frame: baseline to 24 hours post-operatively
Biomarkers of Kidney Injury
Time frame: baseline to 24 hours post-operatively
Cell Cycle Stress
Time frame: baseline to 24 hours post-operatively
Biomarkers of Myocardial Injury
Time frame: baseline to 24 hours post-operatively
Urine Output
Time frame: baseline to 73 hrs post-operatively
Vasopressors Usage
Time frame: baseline to 73 hrs post-operatively
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2018.
Related trials for Acute Kidney Injury
Not yet recruiting
Vitamin C for Acute Kidney Injury in ACLF With Septic Shock: A Randomized Controlled Trial
Acute-on-Chronic Liver Failure (ACLF)
Not yet recruiting
Early Biomarker Kidney Injury Assessment After Acumen Directed Fluid Management in Cardiac Surgery
Renal Injury, Acute Kidney Injury
Recruiting
Acute Kidney Injury and Ultra-endurance Running
AKI (Acute Kidney Injury) Due to Trauma
Recruiting
WIN Ratio Analysis to Determine a Strategy of Non- Invasive SUpport for Respiratory Failure in the EmeRgency Department
Acute Hypoxic Respiratory Failure, Acute Respiratory Distress Syndrome (ARDS)
Not yet recruitingObservational study
Diastolic Shock Index for Predicting Hemodynamic Instability During Continuous Renal Replacement Therapy
Acute Kidney Injury, Hypotension (MeSH: D007022)
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.
Ahmed F Zaky, MD principal investigator
University of Alabama at Birmingham
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 Saline and Sodium Nitrite in people with Acute Kidney Injury, run by University of Alabama at Birmingham 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 11 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: withdrawn, as of the sponsor's last update on 27 Sep 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 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. 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 was withdrawn before enrolling participants, so there are no results.
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?
Nitrite Metabolome Levels (time frame: baseline to 73 hrs post-operatively). The study lists 4 primary outcomes in all. 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 27 Sep 2018.