Clinical trial NCT06706258: Post-Cardiac Surgery Acute Kidney Injury Prevention by Administration of Proton Pump Inhibitor (P2 Trial)
Official title: Post-Cardiac Surgery Acute Kidney Injury Prevention by Administration of Proton Pump Inhibitor (P2 Trial): A Prospective Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Kidney Injury
Keywords: Acute Kidney Injury
AKI
Cardiac Surgery
Cardiovascular Surgery
PPI
Proton Pump Inhibitors
Perioperative Medicine
Anesthesiology
Intensive Care Unit
ICU
Kidney
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
First posted: 2024-11-26
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Incidence of Acute Kidney Injury (AKI)
timeFrame: From enrollment to 7 days or until hospital discharge, if earlier.
Secondary outcomes:
measure: Urinary Kidney Injury Biomarkers Levels
timeFrame: From enrollment to 72 hours after ICU admission
measure: Major Adverse Kidney Events (MAKE)
timeFrame: From enrollment to 30 days after cardiac surgery
Other outcomes:
Locations:
city: Houston
country: United States
facility: Memorial Hermann Texas Medical Center
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Yafen Liang, MD
role: PRINCIPAL_INVESTIGATOR
References: