Pantoprazole for Acute Kidney Injury Prevention After Cardiac Surgery

(P2 AKI PPI Trial)

Overseen By Simon Betancourt Escobar, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The University of Texas Health Science Center, Houston

Disqualifiers: Low eGFR, Dialysis, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 2 days

400 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug pantoprazole for preventing acute kidney injury after cardiac surgery?

Research shows that pantoprazole has anti-inflammatory effects and can protect against kidney damage in rats, suggesting it might help prevent kidney injury in humans. ^{1 2 3 4 5}

Is pantoprazole generally safe for humans?

Pantoprazole is generally safe for humans, but there are some risks. It has been associated with a rare side effect called acute interstitial nephritis (a type of kidney inflammation), which can lead to kidney failure if not treated. This condition was successfully treated in a reported case by stopping pantoprazole and using corticosteroids (a type of anti-inflammatory medication). ^{1 4 5 6 7}

How is the drug Pantoprazole unique for preventing acute kidney injury after cardiac surgery?

Pantoprazole is unique because it is primarily a proton pump inhibitor (a type of drug that reduces stomach acid) and is being explored for a novel use in preventing acute kidney injury after cardiac surgery, a condition for which there are currently no specific pharmacological therapies. ^{8 9 10 11 12}

What is the purpose of this 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.

Research Team

Yafen Liang, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Eligibility Criteria

Adult patients over 18 years old scheduled for cardiac surgery using a cardiopulmonary bypass machine are eligible for this trial. The study specifically aims to prevent acute kidney injury post-surgery.

Inclusion Criteria

Patients with a moderate to high risk of developing AKI (Cleveland risk score equal to or higher than 3)

Exclusion Criteria

Patients with vitamin B12 deficiency

My kidney function is low, with an eGFR under 30.

I depend on dialysis for kidney function.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either pantoprazole or famotidine perioperatively for 2 days

2 days

6 visits (in-person) during hospital stay

Initial Follow-up

Participants are monitored for acute kidney injury within 7 days or until hospital discharge

7 days

Extended Follow-up

Participants are monitored for major adverse kidney events (MAKE) and urinary biomarkers up to 30 days post-surgery

30 days

Treatment Details

Interventions

• Pantoprazole

Trial Overview The trial is testing if pantoprazole, a proton pump inhibitor, can protect against kidney damage after heart surgery better than famotidine. Patients will be randomly assigned to receive either pantoprazole or famotidine intravenously for two days around the time of their operation.

Participant Groups

Group I: Pantoprazole Group Experimental Treatment 1 Intervention

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 II: Famotidine Group Active Control 1 Intervention

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.

Pantoprazole is already approved in United States, European Union, Canada, Japan, China, Switzerland for the following indications:

Approved in United States as Protonix for:

• Erosive esophagitis
• Gastroesophageal reflux disease (GERD)
• Zollinger-Ellison syndrome

Approved in European Union as Pantoprazole for:

• Erosive esophagitis
• Gastroesophageal reflux disease (GERD)
• Zollinger-Ellison syndrome
• Peptic ulcer disease

Approved in Canada as Pantoprazole for:

• Erosive esophagitis
• Gastroesophageal reflux disease (GERD)
• Zollinger-Ellison syndrome

Approved in Japan as Pantoprazole for:

• Erosive esophagitis
• Gastroesophageal reflux disease (GERD)
• Zollinger-Ellison syndrome

Approved in China as Pantoprazole for:

• Erosive esophagitis
• Gastroesophageal reflux disease (GERD)
• Zollinger-Ellison syndrome

Approved in Switzerland as Pantoprazole for:

• Erosive esophagitis
• Gastroesophageal reflux disease (GERD)
• Zollinger-Ellison syndrome

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

Findings from Research

In a study involving male Wistar rats, pretreatment with pantoprazole at doses of 18 and 36 mg/kg significantly improved renal function by reducing serum creatinine and blood urea nitrogen levels after renal ischemia/reperfusion injury.

Pantoprazole also decreased oxidative stress markers and toll-like receptor 4 (TLR-4) expression in renal tissue, suggesting its protective effects against kidney damage are linked to its anti-inflammatory properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The protective effect of acute pantoprazole pretreatment on renal ischemia/reperfusion injury in rats. Kohansal, P., Rajai, N., Dehpour, AR., et al.[2019]

Pantoprazole sodium, when stored in polypropylene syringes at 2°C to 8°C, remains stable for up to 28 days, making it a reliable option for short-term treatment of conditions like ulcers and gastroesophageal reflux disease.

The study confirmed that pantoprazole diluted in PVC minibags is stable for 14 days at 2°C to 8°C and for 3 days at room temperature, ensuring its efficacy and safety during storage and administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stability of pantoprazole sodium in glass vials, polyvinyl chloride minibags, and polypropylene syringes. Donnelly, RF.[2022]

In a study involving 202 outpatients, pantoprazole (40 mg) demonstrated a significantly higher healing rate for acute duodenal ulcers compared to ranitidine (300 mg), with 81% healing after 2 weeks versus 53% for ranitidine (P < 0.001).

After 4 weeks, pantoprazole continued to show superior efficacy with a healing rate of 97% compared to 83% for ranitidine (P < 0.01), and both treatments were well tolerated by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of pantoprazole and ranitidine in the treatment of acute duodenal ulcer. Pantoprazole-Duodenal Ulcer-Study Group. Judmaier, G., Koelz, HR.[2019]

A case study of a 23-year-old man revealed that acute interstitial nephritis can develop after just 6 weeks of treatment with pantoprazole, a commonly prescribed proton-pump inhibitor.

The condition was diagnosed through a renal biopsy and successfully treated with corticosteroids and discontinuation of pantoprazole, highlighting the need for awareness of potential kidney-related side effects of PPIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pantoprazole-induced acute interstitial nephritis. Moore, I., Sayer, JA., Nayar, A., et al.[2018]

In a clinical trial involving 163 patients with duodenal ulcers, pantoprazole showed a significantly higher healing rate at 72% compared to 51% for ranitidine after 2 weeks, indicating its superior efficacy.

Both pantoprazole and ranitidine were well tolerated and safe, but pantoprazole also led to a faster reduction in pain for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Superiority of pantoprazole over ranitidine in the treatment of duodenal ulcer. Mexican clinical experience. Mexican Study Group of Pantoprazole++ in Duodenal Ulcer]. Dibildox, M., Rose, K., Tomás-Pons, J., et al.[2018]

In a study of 286 patients with reflux oesophagitis, both pantoprazole (40 mg) and omeprazole (20 mg) demonstrated similar healing rates after 4 weeks (74% vs. 78%) and 8 weeks (90% vs. 94%), indicating comparable efficacy in treating the condition.

Both medications were well tolerated by patients, suggesting that they are safe options for treating mild to moderate reflux oesophagitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind study of pantoprazole and omeprazole in the treatment of reflux oesophagitis: a multicentre trial. Mössner, J., Hölscher, AH., Herz, R., et al.[2019]

In a study of 219 patients with benign gastric ulcers, pantoprazole (40 mg) demonstrated a higher healing rate after 4 weeks (88%) compared to omeprazole (77%), indicating its efficacy as a treatment.

Both pantoprazole and omeprazole were found to be equally safe, with only 10% of patients in each group reporting adverse events, suggesting that pantoprazole is a well-tolerated option for treating gastric ulcers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pantoprazole versus omeprazole in the treatment of acute gastric ulcers. Witzel, L., Gütz, H., Hüttemann, W., et al.[2019]

Acute kidney injury (AKI) affects up to 30% of patients recovering from cardiac surgery and significantly increases the risk of death during hospitalization by five times, highlighting the critical need for effective preventive strategies.

Current evidence suggests that maintaining renal perfusion, using balanced salt intravenous fluids, and minimizing exposure to cardiopulmonary bypass can help prevent AKI, which is crucial since 2-5% of patients may require renal replacement therapy, associated with a 50% mortality rate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute kidney injury following cardiac surgery: current understanding and future directions. O'Neal, JB., Shaw, AD., Billings, FT.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

The protective effect of acute pantoprazole pretreatment on renal ischemia/reperfusion injury in rats. [2019]

2. Canada pubmed.ncbi.nlm.nih.gov

Stability of pantoprazole sodium in glass vials, polyvinyl chloride minibags, and polypropylene syringes. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Comparison of pantoprazole and ranitidine in the treatment of acute duodenal ulcer. Pantoprazole-Duodenal Ulcer-Study Group. [2019]

4. Italy pubmed.ncbi.nlm.nih.gov

Pantoprazole-induced acute interstitial nephritis. [2018]

5. Mexico pubmed.ncbi.nlm.nih.gov

[Superiority of pantoprazole over ranitidine in the treatment of duodenal ulcer. Mexican clinical experience. Mexican Study Group of Pantoprazole++ in Duodenal Ulcer]. [2018]

6. England pubmed.ncbi.nlm.nih.gov

A double-blind study of pantoprazole and omeprazole in the treatment of reflux oesophagitis: a multicentre trial. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Pantoprazole versus omeprazole in the treatment of acute gastric ulcers. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Cardiac Surgery Associated AKI Prevention Strategies and Medical Treatment for CSA-AKI. [2021]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Recent Perioperative Pharmacological Prevention of Acute Kidney Injury after Cardiac Surgery: A Narrative Review. [2018]

10. Korea (South) pubmed.ncbi.nlm.nih.gov

Urinary Biomarkers may Complement the Cleveland Score for Prediction of Adverse Kidney Events After Cardiac Surgery: A Pilot Study. [2020]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Development and internal validation of a prediction model for acute kidney injury following cardiac valve replacement surgery. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Acute kidney injury following cardiac surgery: current understanding and future directions. [2022]