Pantoprazole for Acute Kidney Injury Prevention Post-Cardiac Surgery

Overseen By Connor Rollings, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The University of Texas Health Science Center, Houston

Must not be taking: Proton pump inhibitors

Disqualifiers: Dialysis, Pregnancy, Liver disease, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 days

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 protect kidneys after heart surgery better than famotidine (an H2 blocker). Researchers aim to determine if pantoprazole improves kidney health and reduces the risk of acute kidney injury (AKI), a serious post-surgery concern. Individuals scheduled for elective heart surgery with a heart-lung machine, and identified by their doctor as at moderate to high risk for kidney issues, might be suitable candidates for this trial. As a Phase 2 trial, this research measures pantoprazole's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant medical advancements.

Do I need to stop taking my current medications for this trial?

The protocol does not specify if you need to stop taking your current medications. However, if you are taking proton pump inhibitors (PPIs) and have a hypersensitivity to them, you may be excluded from the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that pantoprazole is generally easy for most people to handle. Studies have found that hospitals often use it because it is safe and doesn't usually cause serious side effects. Pantoprazole is already approved for treating conditions related to stomach acid, so doctors understand its mechanism.

Famotidine is another option. It is also considered safe and commonly used to lower stomach acid. Many people take famotidine without any problems.

Researchers are testing both drugs to see if they can help prevent kidney issues after heart surgery. So far, their regular use in other treatments supports their safety. Always consult a doctor if you have questions about joining a trial. ^{1 2 3 4 5}

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

Researchers are excited about these treatments because pantoprazole and famotidine might offer new ways to prevent acute kidney injury after heart surgery. Unlike current options that mainly manage symptoms, pantoprazole is being tested for its ability to protect kidney function directly during high-stress surgeries. Pantoprazole works by reducing stomach acid, which might help by minimizing stress on kidneys during major operations. Meanwhile, famotidine, another acid-reducer, is being studied for similar potential benefits. If successful, these treatments could be a game-changer by providing direct kidney protection in a critical surgical setting.

What evidence suggests that this trial's treatments could be effective for preventing acute kidney injury post-cardiac surgery?

Research suggests that pantoprazole, a medication that reduces stomach acid, might help prevent sudden kidney problems after heart surgery. While animal studies have shown positive results, human studies remain limited. Researchers aim to determine whether pantoprazole can improve kidney function post-surgery. In this trial, participants will receive either pantoprazole or famotidine, another acid-reducing medication. Famotidine is often used but lacks specific evidence for preventing kidney issues in this context. This study compares the two treatments to identify which better protects the kidneys after heart surgery. ^{1 2 3 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?

This trial is for adults scheduled for elective cardiac surgery with a high risk of acute kidney injury (AKI), as indicated by a Cleveland risk score over 6. They must have normal preoperative kidney function and not be on dialysis, pregnant, nursing, allergic to PPIs, or have liver disease or vitamin B12 deficiency.

Inclusion Criteria

I am scheduled for heart surgery with a high risk of kidney injury.

Exclusion Criteria

I need surgery urgently.

I have a liver condition.

I depend on dialysis for kidney function.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either pantoprazole or famotidine perioperatively for 2 days

2 days

In-hospital during surgery

Immediate Postoperative Monitoring

Monitoring of kidney injury biomarkers (KIM-1 and NGAL) at 8, 24, and 48 hours postoperatively

48 hours

Follow-up

Participants are monitored for major adverse kidney events and AKI incidence up to 30 days post-surgery

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Famotidine
• Pantoprazole

Trial Overview The study tests if intravenous pantoprazole can improve kidney function and reduce AKI after heart surgery using cardiopulmonary bypass compared to famotidine. It also looks at the effect on major adverse kidney events.

How Is the Trial Designed?

Group I: Pantoprazole group Experimental Treatment 1 Intervention

Pantoprazole (40 mg iv every 12 hours/q12H) for 2 days perioperatively (first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on postoperative (POD) 1 for a total of 4 doses over 2 days. There will be no other modifications in patient care.

Group II: Famotidine Group Active Control 1 Intervention

Famotidine (20 mg iv q12H) for 2 days perioperatively (first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on POD 1 for a total of 4 doses over 2 days. There will be no other modifications in patient care.

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

Approved in United States as Pepcid for:

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

Approved in European Union as Famotidine for:

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

Approved in Canada as Pepcid for:

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

Approved in Japan as Famotidine for:

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

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

Society of Cardiovascular Anesthesiologists

Collaborator

Trials

3

Recruited

5,600+

Published Research Related to This Trial

In a study of 50 patients undergoing simultaneous pancreas-kidney (SPK) transplantation, a quadruple immunosuppressive regimen including rabbit antithymocyte globulin (ATG) significantly reduced the incidence of acute renal rejection episodes compared to a triple regimen with cyclosporine (CsA), azathioprine, and corticosteroids (36% vs. 76%).

Despite a higher rate of adverse events in the ATG group (80% vs. 40%), none led to drug discontinuation, and there were no differences in overall patient, pancreas, or kidney survival rates between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized comparison of triple therapy and antithymocyte globulin induction treatment after simultaneous pancreas-kidney transplantation. Cantarovich, D., Karam, G., Giral-Classe, M., et al.[2013]

In a study of 136 simultaneous pancreas-kidney transplant recipients, alemtuzumab was found to significantly reduce the incidence of acute cellular rejection (ACR) compared to basiliximab (3.1% vs. 12.8% over 2 years), indicating its efficacy in preventing this type of rejection.

While both induction agents showed similar rates of antibody-mediated rejection (AMR), the study revealed that AMR was more common in patients treated with alemtuzumab, highlighting a complex balance in rejection types and suggesting that while ACR is better managed with alemtuzumab, AMR remains a concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alemtuzumab induction and antibody-mediated kidney rejection after simultaneous pancreas-kidney transplantation. Pascual, J., Pirsch, JD., Odorico, JS., et al.[2017]

In a study of 724 kidney transplant recipients, basiliximab (BSX) was found to have similar efficacy and safety outcomes compared to antithymocyte globulin (ATG) in deceased donor kidney transplantation, regardless of donor characteristics like age and kidney condition.

There were no significant differences in rates of acute rejection, delayed graft function, infections, or survival between the two induction agents, suggesting that BSX can be a viable alternative to ATG even in cases with poorer donor conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The comparative efficacy and safety of basiliximab and antithymocyte globulin in deceased donor kidney transplantation: a multicenter cohort study. Hong, SY., Kim, YS., Jin, K., et al.[2023]

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]

Over the past decade, there has been a significant shift in immunosuppression strategies for solid-organ transplantation, with a notable increase in the use of induction therapy using antibodies, particularly among kidney and pancreas transplant recipients.

The combination of tacrolimus and mycophenolate mofetil has become the most common discharge regimen, and there is a growing trend towards steroid-avoidance protocols, contributing to a decline in acute rejection rates post-transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunosuppression: evolution in practice and trends, 1994-2004. Meier-Kriesche, HU., Li, S., Gruessner, RW., et al.[2023]

In a 2-year study involving 157 outpatients with healed reflux oesophagitis, pantoprazole (40 mg daily) demonstrated significant efficacy, with endoscopic remission rates of 87% at 12 months and 76% at 24 months.

The treatment was found to be safe, with only 7% of adverse events potentially related to the medication, and a manageable increase in serum gastrin levels over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pantoprazole 40 mg daily as relapse prophylaxis in patients with healed reflux oesophagitis-a 2-year follow-up. Van Rensburg, CJ., Honiball, PJ., Van Zyl, JH., et al.[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]

Despite the use of various immunosuppressive induction agents since 1987, the rate of chronic pancreas graft loss in simultaneous pancreas-kidney transplantation has not improved, indicating a persistent challenge in long-term graft survival.

While these agents have successfully enhanced short-term survival by preventing acute rejection, they have not effectively addressed chronic rejection, highlighting the need for new strategies to improve long-term outcomes in transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous pancreas-kidney transplantation in the United States: an analysis of the UNOS registry. Waki, K., Sugawara, Y., Tamura, S., et al.[2011]

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 9860 cardiac surgery patients, preoperative exposure to proton pump inhibitors (PPIs) was linked to a higher incidence of acute kidney injury (AKI) and AKI requiring dialysis, with adjusted odds ratios indicating a significant risk increase.

Discontinuing PPIs before surgery was associated with a reduced risk of developing AKI, suggesting that managing PPI use could be an important strategy to improve patient outcomes in cardiac surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Proton Pump Inhibitor Exposure and Acute Kidney Injury After Cardiac Surgery. Koh, HB., Joo, YS., Kim, HW., et al.[2023]

Proton pump inhibitors (PPIs) may be linked to an increased risk of acute interstitial nephritis (AIN), but the evidence is not definitive and requires further investigation with more cases for clarity.

Traditional nonsteroidal anti-inflammatory drugs (tNSAIDs) are associated with a significantly higher risk of acute kidney injury (AKI), with odds ratios indicating a clear relationship between tNSAID use and kidney damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton pump inhibitors and traditional nonsteroidal anti-inflammatory drugs and the risk of acute interstitial nephritis and acute kidney injury. Leonard, CE., Freeman, CP., Newcomb, CW., et al.[2016]

In a study of 236 renal transplant patients, only 8% experienced upper gastrointestinal complications, indicating a low incidence of such issues post-transplant.

There was no significant difference in complication rates between patients treated with omeprazole or ranitidine for ulcer prevention, nor between those on tacrolimus or cyclosporin for immunosuppression, suggesting that both treatment strategies are equally effective in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upper gastrointestinal complications after renal transplantation: a 3-yr sequential study. Logan, AJ., Morris-Stiff, GJ., Bowrey, DJ., et al.[2019]

In a study involving 578 patients with gastro-oesophageal reflux disease (GERD), pantoprazole magnesium (pantoprazole-Mg) was found to be as effective as esomeprazole in achieving complete remission after 4 weeks of treatment, with both medications showing a 61% success rate.

At 8 weeks, pantoprazole-Mg provided significantly greater symptom relief compared to esomeprazole (91.6% vs. 86.0%), indicating that pantoprazole-Mg may offer an extended therapeutic effect beyond the initial treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised clinical trial: daily pantoprazole magnesium 40 mg vs. esomeprazole 40 mg for gastro-oesophageal reflux disease, assessed by endoscopy and symptoms. Moraes-Filho, JP., Pedroso, M., Quigley, EM.[2018]

Citations

1. 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 ...

2. 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 ...

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06154226/prevention-of-post-cardiac-surgery-acute-kidney-injury-by-proton-pump-inhibitor

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 ...

4. ctv.veeva.com ctv.veeva.com/study/post-cardiac-surgery-acute-kidney-injury-prevention-by-administration-of-proton-pump-inhibitor-p2-t

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) ...

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

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

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. go.drugbank.com go.drugbank.com/drugs/DB00213/clinical_trials?conditions=DBCOND0068886&phase=2&purpose=prevention&status=completed

Pantoprazole Completed Phase 2 Trials for Acute Kidney ... Pantoprazole Completed Phase 2 Trials for Acute Kidney Injury (AKI) Prevention ... Prevention of Post-Cardiac Surgery Acute Kidney Injury by Proton Pump Inhibitor.