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| Name | Class |
|---|---|
| Society of Cardiovascular Anesthesiologists | UNKNOWN |
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The purpose of this study is to determine whether perioperative intravenous administration of pantoprazole will improve kidney function parameters following cardiac surgery with cardiopulmonary bypass compared to famotidine and to determine whether perioperative intravenous administration of pantoprazole will decrease the incidence of postoperative Acte Kidney Injury (AKI) and major adverse kidney events (MAKE).
Each year more than 500,000 cardiac surgeries are performed in the United States of America (USA) alone. Acute kidney injury (AKI) is a common complication following cardiac surgery and is associated with poor patient outcomes and increased healthcare costs. Therefore, there is an urgent need to identify medical interventions and treatments that prevent AKI or mitigate its severity when it occurs after cardiac surgery.
One of the main causes of AKI following cardiac surgery involves renal hypoperfusion/ischemia and reperfusion injury. Hypoxia-inducible factors (HIFs) are key transcription factors responsible for tissue adaptation to low oxygen, which orchestrate the expression of a wide variety of genes including a set of micro-ribonucleic acid (microRNAs). MicroRNAs are endogenous single-stranded noncoding miRNAs of nucleotides that participate in physiological and pathological functions via regulating post-transcription of target genes. During ischemic injury, hypoxia upregulates endothelial MicroRNAs that has the potential in renal protection through vascular integrity and regeneration. Additionally, microRNAs exert protective effects via decreasing apoptosis and promoting tubular cell proliferation during ischemic AKI.
Moreover, decreased serum levels of MicroRNAs are highly correlated with AKI severity in the intensive care unit (ICU) patients. Our preliminary study identified ATP4A as the downstream target gene of MicroRNAs in the kidney. Adenosine triphosphate (ATP)4A (catalytic α subunit of H+/K+ ATPase) is located in intercalated cells in the distal tubules and cortical collecting ducts, which regulates urine acidification through secretion of hydrogen and reabsorption of potassium from urine. Proton pump inhibitors (PPIs) block the ATP hydrolysis of the H+/K+ ATPase via binding its active site of ATP4A and further enhance this endogenous kidney protection pathway. Despite robust animal model data, randomized controlled trial aiming to test the effectiveness of PPI in post-cardiac surgery AKI prevention is lacking. If proven to be effective, our studies could be easily implemented in clinical practice and serve as an effective treatment for perioperative AKI.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pantoprazole | Experimental | Pantoprazole (40 mg iv every 12 hours/q12H) for 2 days perioperatively [first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on postoperative (POD) 1 for a total of 4 doses over 2 days]. There will be no other modifications in patient care. |
|
| Famotidine | Active Comparator | Famotidine (20 mg iv q12H) for 2 days perioperatively [first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on POD 1 for a total of 4 doses over 2 days]. There will be no other modifications in patient care. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pantoprazole | Drug | Subjects will receive pantoprazole (40 mg iv q12H) for 2 days perioperatively [first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on post operative day 1 (POD 1) for a total of 4 doses over 2 days]. |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve (AUC) of Urinary Kidney Injury Biomarker Kidney Injury Molecule-1 (KIM-1) Above Baseline Within 24 Hours Postoperatively | The area under the curve (AUC) is a summary measure of the concentration of the biomarker over time and is expressed as (ng*h/mL). | from baseline (time 0) to 24 hours postoperatively |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve (AUC) of Urinary Kidney Injury Biomarker Neutrophil Gelatinase-associated Lipocalin (NGAL) Above Baseline Within 24 Hours Postoperatively | The area under the curve (AUC) is a summary measure of the concentration of the biomarker over time and is expressed as (ng*h/mL). | from baseline (time 0) to 24 hours postoperatively |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Yafen Liang, MD | The University of Texas Health Science Center, Houston | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The University of Texas Health Science Center at Houston | Houston | Texas | 77030 | United States |
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All 100 participants completed the study; however, upon further verification before analysis, 2 participants who completed (1 per arm) were deemed to not meet the inclusion criteria; therefore, these 2 participants (1 per arm) were excluded from the analysis.
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| ID | Title | Description |
|---|---|---|
| FG000 | Famotidine Group | Famotidine (20 mg iv q12H) for 2 days perioperatively (first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on POD 1 for a total of 4 doses over 2 days. There will be no other modifications in patient care. Famotidine: Subjects will receive famotidine (20 mg iv q12H) for 2 days perioperatively (first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on POD 1 for a total of 4 doses over 2 days. |
| FG001 | Pantoprazole Group | Pantoprazole (40 mg iv every 12 hours/q12H) for 2 days perioperatively (first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on postoperative (POD) 1 for a total of 4 doses over 2 days. There will be no other modifications in patient care. Pantoprazole: Subjects will receive pantoprazole (40 mg iv q12H) for 2 days perioperatively (first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on post operative day 1 (POD 1) for a total of 4 doses over 2 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Famotidine Group | Famotidine (20 mg iv q12H) for 2 days perioperatively (first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on POD 1 for a total of 4 doses over 2 days. There will be no other modifications in patient care. Famotidine: Subjects will receive famotidine (20 mg iv q12H) for 2 days perioperatively (first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on POD 1 for a total of 4 doses over 2 days. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Curve (AUC) of Urinary Kidney Injury Biomarker Kidney Injury Molecule-1 (KIM-1) Above Baseline Within 24 Hours Postoperatively | The area under the curve (AUC) is a summary measure of the concentration of the biomarker over time and is expressed as (ng*h/mL). | All 100 participants completed the study; however, upon further verification before analysis, 2 participants who completed (1 per arm) were deemed to not meet the inclusion criteria; therefore, these 2 participants (1 per arm) were excluded from the analysis. An intent-to-treat analysis is reported. | Posted | Median | Inter-Quartile Range | ng*h/mL | from baseline (time 0) to 24 hours postoperatively |
|
30 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Famotidine Group | Famotidine (20 mg iv q12H) for 2 days perioperatively (first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on POD 1 for a total of 4 doses over 2 days. There will be no other modifications in patient care. Famotidine: Subjects will receive famotidine (20 mg iv q12H) for 2 days perioperatively (first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on POD 1 for a total of 4 doses over 2 days. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastrointestinal bleeding | Gastrointestinal disorders | Systematic Assessment | Data and Safety Monitoring Board (DSMB) determined adverse event was not related to the intervention. |
The AUC values have low sensitivity for detecting differences between arms as a result of limited timepoints.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Yafen Liang, MD | The University of Texas Health Science Center at Houston | (713) 500-6229 | Yafen.Liang@uth.tmc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 2, 2024 | Sep 12, 2025 | Prot_003.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 26, 2024 | Sep 12, 2025 | SAP_004.pdf |
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| ID | Term |
|---|---|
| D058186 | Acute Kidney Injury |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| D000077402 | Pantoprazole |
| D015738 | Famotidine |
| ID | Term |
|---|---|
| D053799 | 2-Pyridinylmethylsulfinylbenzimidazoles |
| D013454 | Sulfoxides |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
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The outcome assessor who tests the urinary kidney injury biomarkers is blinded.
|
| Famotidine | Drug | Subjects will receive famotidine (20 mg iv q12H) for 2 days perioperatively [first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on POD 1 for a total of 4 doses over 2 days]. |
|
| Area Under the Curve (AUC) of Urinary Kidney Injury Biomarker Tissue Inhibitor of Metalloproteinases 2 (TIMP-2) Above Baseline Within 24 Hours Postoperatively | The area under the curve (AUC) is a summary measure of the concentration of the biomarker over time and is expressed as (ng*h/mL). | from baseline (time 0) to 24 hours postoperatively |
| Area Under the Curve (AUC) of Urinary Kidney Injury Biomarker Insulin-like Growth Factor-binding Protein 7 (IGFBP-7) Above Baseline Within 24 Hours Postoperatively | The area under the curve (AUC) is a summary measure of the concentration of the biomarker over time and is expressed as (ng*h/mL). | from baseline (time 0) to 24 hours postoperatively |
| Number of Participants With Any-stage Postoperative Acute Kidney Injury (AKI) | Acute kidney injury (AKI) will be defined using the 2012 Kidney Disease Improving Global Outcomes (KDIGO) criteria: serum creatinine (SCr) increase greater than 50% from baseline or ≥ 0.3 mg/dL increase within 48 hours after surgery. | from baseline to postoperative day 7 (or hospital discharge if earlier) |
| Number of Participants With Major Adverse Kidney Events (MAKE) | MAKE is defined as the composite of death, dialysis, renal hospitalization or sustained kidney dysfunction defined as glomerular filtration rate (GFR) decline of 25% or more from preoperative baseline. | from baseline to 30 days after surgery |
| BG001 | Pantoprazole Group | Pantoprazole (40 mg iv every 12 hours/q12H) for 2 days perioperatively (first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on postoperative (POD) 1 for a total of 4 doses over 2 days. There will be no other modifications in patient care. Pantoprazole: Subjects will receive pantoprazole (40 mg iv q12H) for 2 days perioperatively (first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on post operative day 1 (POD 1) for a total of 4 doses over 2 days. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Pantoprazole Group | Pantoprazole (40 mg iv every 12 hours/q12H) for 2 days perioperatively (first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on postoperative (POD) 1 for a total of 4 doses over 2 days. There will be no other modifications in patient care. Pantoprazole: Subjects will receive pantoprazole (40 mg iv q12H) for 2 days perioperatively (first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on post operative day 1 (POD 1) for a total of 4 doses over 2 days. |
|
|
| Secondary | Area Under the Curve (AUC) of Urinary Kidney Injury Biomarker Neutrophil Gelatinase-associated Lipocalin (NGAL) Above Baseline Within 24 Hours Postoperatively | The area under the curve (AUC) is a summary measure of the concentration of the biomarker over time and is expressed as (ng*h/mL). | All 100 participants completed the study; however, upon further verification before analysis, 2 participants who completed (1 per arm) were deemed to not meet the inclusion criteria; therefore, these 2 participants (1 per arm) were excluded from the analysis. An intent-to-treat analysis is reported. | Posted | Median | Inter-Quartile Range | ng*h/mL | from baseline (time 0) to 24 hours postoperatively |
|
|
|
| Secondary | Area Under the Curve (AUC) of Urinary Kidney Injury Biomarker Tissue Inhibitor of Metalloproteinases 2 (TIMP-2) Above Baseline Within 24 Hours Postoperatively | The area under the curve (AUC) is a summary measure of the concentration of the biomarker over time and is expressed as (ng*h/mL). | Data for the biomarker TIMP-2 were not collected. This is because in a prior non-interventional validation study, IGFBP-7 could not be validated with ELISA, and because a combination of TIMP-2 and IGFBP-7 are used to predict AKI risk, it was determined that TIMP-2 (which depends on IGFBP-7) will not be used used to predict AKI risk in this trial. The Study Protocol was not amended to reflect this collective team decision. Data collection and analysis will not be conducted in the future. | Posted | Median | Inter-Quartile Range | ng*h/mL | from baseline (time 0) to 24 hours postoperatively |
|
|
| Secondary | Area Under the Curve (AUC) of Urinary Kidney Injury Biomarker Insulin-like Growth Factor-binding Protein 7 (IGFBP-7) Above Baseline Within 24 Hours Postoperatively | The area under the curve (AUC) is a summary measure of the concentration of the biomarker over time and is expressed as (ng*h/mL). | Data for the biomarker IGFBP-7 were not collected. This is because in a prior non-interventional validation study, IGFBP-7 could not be validated with ELISA; therefore, it was determined that the IGFBP-7 biomarker will not be used used to predict AKI risk in this trial. The Study Protocol was not amended to reflect this collective team decision. Data collection and analysis will not be conducted in the future. | Posted | Median | Inter-Quartile Range | ng*h/mL | from baseline (time 0) to 24 hours postoperatively |
|
|
| Secondary | Number of Participants With Any-stage Postoperative Acute Kidney Injury (AKI) | Acute kidney injury (AKI) will be defined using the 2012 Kidney Disease Improving Global Outcomes (KDIGO) criteria: serum creatinine (SCr) increase greater than 50% from baseline or ≥ 0.3 mg/dL increase within 48 hours after surgery. | All 100 participants completed the study; however, upon further verification before analysis, 2 participants who completed (1 per arm) were deemed to not meet the inclusion criteria; therefore, these 2 participants (1 per arm) were excluded from the analysis. An intent-to-treat analysis is reported. | Posted | Count of Participants | Participants | from baseline to postoperative day 7 (or hospital discharge if earlier) |
|
|
|
| Secondary | Number of Participants With Major Adverse Kidney Events (MAKE) | MAKE is defined as the composite of death, dialysis, renal hospitalization or sustained kidney dysfunction defined as glomerular filtration rate (GFR) decline of 25% or more from preoperative baseline. | All 100 participants completed the study; however, upon further verification before analysis, 2 participants who completed (1 per arm) were deemed to not meet the inclusion criteria; therefore, these 2 participants (1 per arm) were excluded from the analysis. An intent-to-treat analysis is reported. | Posted | Count of Participants | Participants | from baseline to 30 days after surgery |
|
|
|
| 1 |
| 50 |
| 0 |
| 50 |
| 3 |
| 50 |
| EG001 | Pantoprazole Group | Pantoprazole (40 mg iv every 12 hours/q12H) for 2 days perioperatively (first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on postoperative (POD) 1 for a total of 4 doses over 2 days. There will be no other modifications in patient care. Pantoprazole: Subjects will receive pantoprazole (40 mg iv q12H) for 2 days perioperatively (first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on post operative day 1 (POD 1) for a total of 4 doses over 2 days. | 1 | 50 | 0 | 50 | 5 | 50 |
|
| Pneumonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Data and Safety Monitoring Board (DSMB) determined adverse event was not related to the intervention. |
|
| Acute interstitial nephritis | Renal and urinary disorders | Systematic Assessment | Data and Safety Monitoring Board (DSMB) determined adverse event was not related to the intervention. |
|
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| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D011725 |
| Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D013844 | Thiazoles |
| D001393 | Azoles |