Prevention of Post-Cardiac Surgery Acute Kidney Injury by Proton Pump Inhibitor

Prevention of Post-Cardiac Surgery Acute Kidney Injury by Proton Pump Inhibitor: A Prospective Randomized Controlled Trial

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).

Study Overview

• Status: Completed
• Conditions: Acute Kidney Injury
• Intervention / Treatment: Drug: Pantoprazole; Drug: Famotidine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Scheduled for elective cardiac surgery with cardio pulmonary bypass (CPB) with a moderate to high risk of developing AKI (Cleveland risk score equal or higher than 3)

Exclusion Criteria:

• Preoperative eGFR<30 ml/min per 1.73 m2
• Dialysis dependence
• Emergency surgery
• Pregnancy
• Nursing Patients
• Interstitial nephritis
• Proton pump inhibitors (PPIs) hypersensitivity
• Liver disease
• Vitamin B12 deficiency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pantoprazole; 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.	Drug: 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].
Active Comparator: Famotidine; 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.	Drug: 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].

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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
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

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: Society of Cardiovascular Anesthesiologists
• Investigators: Principal Investigator: Yafen Liang, MD, The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2024
• Primary Completion (Actual): September 17, 2024
• Study Completion (Actual): October 10, 2024

Study Registration Dates

• First Submitted: November 20, 2023
• First Submitted That Met QC Criteria: November 29, 2023
• First Posted (Actual): December 4, 2023

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: February 17, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: cardiac surgery
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency; Acute Kidney Injury; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiazoles; Azoles; Pantoprazole; Famotidine
• Other Study ID Numbers: HSC-MS-22-0502

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No