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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the drug pantoprazole, a proton pump inhibitor, can prevent acute kidney injury (AKI) after heart surgery. Researchers aim to determine if administering pantoprazole around the time of surgery offers better kidney protection than famotidine. Participants will receive either pantoprazole or famotidine to compare outcomes. The trial seeks adults scheduled for heart surgery using a heart-lung machine who are at moderate to high risk of kidney problems post-surgery. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that pantoprazole is likely to be safe for humans?

Research has shown that pantoprazole is generally safe and well-tolerated. As a proton pump inhibitor (PPI), it helps reduce stomach acid. Pantoprazole is considered safe for use both in hospitals and at home, with most people not experiencing serious side effects.

Other studies have examined pantoprazole's ability to protect the kidneys after heart surgery, and these studies have not identified major safety issues. Some minor side effects, such as headaches or diarrhea, may occur but are uncommon.

The FDA has already approved pantoprazole for treating stomach problems like acid reflux, indicating its safety for general use. Prospective trial participants can find reassurance in this information, although individual experiences may vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for acute kidney injury?

Researchers are excited about pantoprazole for preventing acute kidney injury (AKI) after cardiac surgery because it offers a new approach compared to the standard treatments typically involving hydration and management of blood pressure. Pantoprazole is a proton pump inhibitor, primarily known for reducing stomach acid, but it is being explored for its potential protective effects on the kidneys. Unlike some other treatments that might focus directly on kidney function, pantoprazole could help by reducing inflammation and oxidative stress during surgery, offering a different angle of protection. This novel mechanism of action is what makes pantoprazole stand out and gives researchers hope for better outcomes in AKI prevention.

What evidence suggests that pantoprazole might be an effective treatment for acute kidney injury after cardiac surgery?

This trial will compare the effects of pantoprazole and famotidine in preventing kidney damage after heart surgery. Studies suggest that pantoprazole, which participants in this trial may receive, might help prevent kidney damage post-surgery. Research on animals has shown that pantoprazole can protect kidneys and reduce swelling. This protection could lower the risk of sudden kidney problems after surgery. However, insufficient studies on humans exist to confirm this effect. While the animal research appears promising, more human studies are necessary for confirmation. ^{2 3 4 6 7}

Who Is on the Research Team?

Yafen Liang, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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 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]

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]

Citations

1. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/26/NCT06154226/Prot_000.pdf

Prevention of Post-Cardiac Surgery Acute Kidney Injury by ... Despite robust animal model data, randomized controlled trial aiming to test the effectiveness of PPI in post-cardiac surgery AKI prevention is lacking. If ...

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06706258/post-cardiac-surgery-acute-kidney-injury-prevention-by-administration-of-proton-pump-inhibitor-p2-trial

Post-Cardiac Surgery Acute Kidney Injury Prevention by ... The specific aims of the study will be achieved by randomizing a group of 400 patients to receive pantoprazole (study) or famotidine (control) ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06154226

Prevention of Post-Cardiac Surgery Acute Kidney Injury ... The purpose of this study is to determine whether perioperative intravenous administration of pantoprazole will improve kidney function parameters following ...

4. withpower.com withpower.com/trial/phase-4-acute-kidney-injury-11-2024-6f6fc

Pantoprazole for Acute Kidney Injury Prevention After ... Research shows that pantoprazole has anti-inflammatory effects and can protect against kidney damage in rats, suggesting it might help prevent kidney injury in ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11230723/

The Effects of Pantoprazole on Kidney Outcomes In this post hoc analysis of the COMPASS trial, pantoprazole resulted in a statistically significant greater rate of eGFR decline as compared with placebo.

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK499945/

Pantoprazole - StatPearls - NCBI Bookshelf In both inpatient and outpatient settings, pantoprazole remains a common therapeutic agent due to a favorable safety profile and availability in ...

7. withpower.com withpower.com/trial/phase-4-acute-kidney-injury-11-2023-1a746

Pantoprazole for Acute Kidney Injury Prevention Post ... This trial tests whether the drug pantoprazole (a proton pump inhibitor) can protect kidneys after heart surgery better than famotidine (an H2 blocker).