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

Last updated: May 9, 2025
Sponsor: The University of Texas Health Science Center, Houston
Overall Status: Active - Recruiting

Phase

2

Condition

Kidney Disease

Renal Failure

Kidney Failure

Treatment

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

Pepcid (Famotidine) 20 mg q 12 hrs for 2 days

Protonix (Pantoprazole) 40 mg q 12 hrs for 2 days

Clinical Study ID

NCT06706258
HSC-MS-24-1034
  • Ages 18-90
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

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 higherthan 3.

Exclusion

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 Design

Total Participants: 400
Treatment Group(s): 4
Primary Treatment: Protonix (Pantoprazole) 40 mg q 12 hrs for 3 days
Phase: 2
Study Start date:
January 24, 2025
Estimated Completion Date:
July 01, 2027

Study 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.

Connect with a study center

  • Memorial Hermann Texas Medical Center

    Houston, Texas 77030
    United States

    Active - Recruiting

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