Post-Cardiac Surgery Acute Kidney Injury Prevention by Administration of Proton Pump Inhibitor (P2 Trial) (P2 AKI PPI)

Post-Cardiac Surgery Acute Kidney Injury Prevention by Administration of Proton Pump Inhibitor (P2 Trial): A Prospective Randomized Controlled Trial

The central hypothesis of this research study is that perioperative administration of the proton pump inhibitor (PPI) pantoprazole could reduce the development of acute kidney injury (AKI) following cardiac surgery by activation molecular pathways for kidney protection. The investigators propose a single-center, randomized, controlled, single-blinded trial to determine whether perioperative intravenous administration of pantoprazole will reduce the incidence of AKI, some molecules that can be detected the urine, and major adverse kidney events (MAKE) at day 30 postoperatively, compared to famotidine after cardiac surgery. The specific aims of the study will be achieved by randomizing a group of 400 patients to receive pantoprazole (study) or famotidine (control) for 3 days perioperatively.

Our study population will include any adult patients (aged over 18 years) scheduled for cardiac surgery requiring a cardiopulmonary bypass machine.

Study Overview

• Status: Recruiting
• Conditions: Acute Kidney Injury
• Intervention / Treatment: Drug: Protonix (Pantoprazole) 40 mg q 12 hrs for 3 days; Drug: Pepcid (Famotidine) 20 mg q 12 hrs for 3 days

Detailed Description

Each year more than 500,000 cardiac surgeries are performed in the USA alone. AKI is a common complication following cardiac surgery and is associated with poor patient outcome and increased health care cost. 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 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 have a 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. ATP4A (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 (Estimated): 400
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yafen Liang, MD; Phone Number: 713-500-6226; Email: yafen.liang@uth.tmc.edu
• Study Contact Backup: Name: Simon Betancourt Escobar, MD; Phone Number: 713-500-5739; Email: simon.betancourtescobar.1@uth.tmc.edu

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Memorial Hermann Texas Medical Center
      • Contact: Yafen Liang, MD; Phone Number: 713-500-6226; Email: yafen.liang@uth.tmc.edu
      • Contact: Simon Betancourt Escobar, MD; Phone Number: 713-500-5739; Email: simon.betancourtescobar.1@uth.tmc.edu
      • Principal Investigator: Yafen Liang, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adult patients (age 18-90).
• Scheduled for elective cardiac surgery with cardiopulmonary bypass.
• Moderate to high risk of developing AKI (Cleveland risk score equal to or higher than 3.

Exclusion Criteria:

• Patients with preoperative eGFR<30 ml/min/1.73 m2
• Dialysis dependence
• Emergency surgery
• Pregnancy.
• Nursing patient
• Patients with interstitial nephritis
• 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 Group; Pantoprazole (Protonix) will be given at 6 different timepoints: After anesthesia induction, before surgical incision.; At chest closure. 3 & 4. Every 12 hrs in post operative day 1. 5 & 6. Every 12 hrs in post operative day 2.	Drug: Protonix (Pantoprazole) 40 mg q 12 hrs for 3 days; Administer 1st dose after anesthesia induction before surgical incision, 2nd dose at chest closure. Then, every 12 hrs for 2 more days.
Active Comparator: Famotidine Group; Famotidine (Pepcid) will be given at 6 different timepoints: After anesthesia induction, before surgical incision.; At chest closure. 3 & 4. Every 12 hrs in post operative day 1. 5 & 6. Every 12 hrs in post operative day 2.	Drug: Pepcid (Famotidine) 20 mg q 12 hrs for 3 days; Administer 1st dose after anesthesia induction before surgical incision, 2nd dose at chest closure. Then, every 12 hrs for 2 more days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Acute Kidney Injury (AKI)	The investigators will calculate the incidence of acute kidney injury (AKI) within 7 days (or until hospital discharge if earlier) of cardiac surgery in patients receiving pantoprazole vs. famotidine.	From enrollment to 7 days or until hospital discharge, if earlier.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary Kidney Injury Biomarkers Levels	The investigators will measure the urinary kidney biomarker KIM-1 (kidney injury molecule-1) and neutrophil gelatinase-associated lipocalin (NGAL) levels at the different time points of urine sample collection (baseline, chest closure, and 8, 24, 48 and 72 hrs after ICU admission)	From enrollment to 72 hours after ICU admission
Major Adverse Kidney Events (MAKE)	The investigators will follow up on patients enrolled in the study and ask about patient demise, necessity of dialysis of any type, hospitalizations due to renal problems, or sustained kidney dysfunction after 30 days of enrollment.	From enrollment to 30 days after cardiac surgery

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: November 22, 2024
• First Submitted That Met QC Criteria: November 22, 2024
• First Posted (Actual): November 26, 2024

Study Record Updates

• Last Update Posted (Actual): May 14, 2025
• Last Update Submitted That Met QC Criteria: May 9, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: ICU; Intensive Care Unit; Cardiac Surgery; PPI; Acute Kidney Injury; Kidney; Perioperative Medicine; AKI; Proton Pump Inhibitors; Anesthesiology; Cardiovascular 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; Wounds and Injuries; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Enzyme Inhibitors; Histamine Antagonists; Histamine Agents; Neurotransmitter Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Histamine H2 Antagonists; Pantoprazole; Famotidine
• Other Study ID Numbers: HSC-MS-24-1034

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The IPD will be shared upon request by the journal.
• IPD Sharing Time Frame: IPD will be available and uploaded on clinicaltrials.gov website when it is due.
• IPD Sharing Access Criteria: Accesible through the clinicaltrials.gov website.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

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