Clinical trial NCT06154226: Prevention of Post-Cardiac Surgery Acute Kidney Injury by Proton Pump Inhibitor
Official title: Prevention of Post-Cardiac Surgery Acute Kidney Injury by Proton Pump Inhibitor: A Prospective Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Kidney Injury
Keywords: cardiac surgery
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
Collaborators: name: Society of Cardiovascular Anesthesiologists
First posted: 2023-12-04
Enrollment: 100
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 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).

Detailed description: Each year more than 500,000 cardiac surgeries are performed in the United States of America (USA) alone. Acute kidney injury ( AK) I 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.

Eligibility criteria: 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
* Interstitial nephritis
* Pregnancy
* Nursing Patients
* Proton pump inhibitors (PPIs) hypersensitivity
* Liver disease
* Vitamin B12 deficiency

Primary outcomes:
measure: Kidney Injury Molecule (KIM-1) biomarker changes
timeFrame: Baseline, 8, 24 and 48 hours postoperatively
Secondary outcomes:
measure: Neutrophil gelatinase-associated lipocalin (NGAL) biomarker changes
timeFrame: Baseline, 8, 24 and 48 hours postoperatively
measure: Incidence, severity and duration of any-stage postoperative AKI
timeFrame: Post Operative Day 7 (or hospital discharge if earlier).
measure: Incidence of major adverse kidney events (MAKE)
timeFrame: 30 days after surgery
Other outcomes:
Locations:
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Yafen Liang, MD
role: PRINCIPAL_INVESTIGATOR
References: