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

NCT ID: NCT06706258

Last Updated: 2025-05-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-24
• Study Completion Date: 2027-07-01

Brief Summary

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.

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.

Conditions

Acute Kidney Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Pantoprazole Group

Pantoprazole (Protonix) will be given at 6 different timepoints:

1. After anesthesia induction, before surgical incision.

2. At chest closure. 3 & 4. Every 12 hrs in post operative day 1. 5 & 6. Every 12 hrs in post operative day 2.

Group Type: EXPERIMENTAL

Protonix (Pantoprazole) 40 mg q 12 hrs for 3 days

Intervention Type: DRUG

Administer 1st dose after anesthesia induction before surgical incision, 2nd dose at chest closure. Then, every 12 hrs for 2 more days.

Famotidine Group

Famotidine (Pepcid) will be given at 6 different timepoints:

1. After anesthesia induction, before surgical incision.

2. At chest closure. 3 & 4. Every 12 hrs in post operative day 1. 5 & 6. Every 12 hrs in post operative day 2.

Group Type: ACTIVE_COMPARATOR

Pepcid (Famotidine) 20 mg q 12 hrs for 3 days

Intervention Type: DRUG

Administer 1st dose after anesthesia induction before surgical incision, 2nd dose at chest closure. Then, every 12 hrs for 2 more days.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: lead

Responsible Party

yafen liang

M.D.; Professor; Chief, Division of Cardiovascular Anesthesiology; Vice Chair, Clinical Research

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yafen Liang, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center, Houston

Locations

Memorial Hermann Texas Medical Center

Houston, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Yafen Liang, MD

Role: CONTACT

yafen.liang@uth.tmc.edu

713-500-6226

Simon Betancourt Escobar, MD

Role: CONTACT

simon.betancourtescobar.1@uth.tmc.edu

713-500-5739

Facility Contacts

Yafen Liang, MD

Role: primary

yafen.liang@uth.tmc.edu

713-500-6226

Simon Betancourt Escobar, MD

Role: backup

simon.betancourtescobar.1@uth.tmc.edu

713-500-5739

Other Identifiers

HSC-MS-24-1034

Identifier Type: -

Identifier Source: org_study_id