Anti-Nausea Medications for Preventing Kidney Damage

Recruiting at 1 trial location

Overseen By Melanie Joy, PharmD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Colorado, Denver

Must not be taking: Herbal supplements, Nephrotoxins

Disqualifiers: Kidney cancer, Nephrotoxins, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 1

Duration: 3 days

72 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications, but it requires no changes in chronic medications within 2 weeks before starting. This suggests you should maintain your current medication regimen without changes.

What data supports the effectiveness of the drug Granisetron in preventing kidney damage?

The research indicates that Granisetron, along with other similar drugs like Ondansetron and Palonosetron, does not require dose adjustment in patients with impaired kidney function, suggesting it is less likely to cause kidney damage compared to other drugs that do require adjustments. ^{1 2 3 4 5}

Is it safe to use anti-nausea medications like Granisetron, Ondansetron, and Palonosetron in humans?

Anti-nausea medications such as Granisetron, Ondansetron, and Palonosetron have been reviewed and do not require dose adjustments for patients with impaired kidney function, suggesting they are generally safe for use in humans. ^{1 6 7 8 9}

How does this drug prevent kidney damage differently from other treatments?

The treatment uses anti-nausea medications, specifically 5-HT3 receptor antagonists like ondansetron and granisetron, which are typically used to prevent nausea and vomiting in chemotherapy patients. This approach is unique because it repurposes these drugs to potentially prevent kidney damage, which is not their standard use. ^{10 11 12 13 14}

What is the purpose of this trial?

This study is being done to determine 1) whether drugs to treat cisplatin-related nausea can influence harm to the kidneys, 2) whether cisplatin levels in the body can influence the risk of harm to the kidneys, and 3) whether a person's genetic make-up can increase or decrease the likelihood of kidney injury due to cisplatin therapy.

Research Team

Edgar Jaimes, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Melanie Joy, PharmD, PhD

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

This trial is for adults aged 18-80 who are prescribed cisplatin for treatment and have healthy kidneys (eGFR > 60 ml/min^2) and liver. Participants should not be pregnant, breastfeeding, or have a history of heavy alcohol use. They must avoid grapefruit juice, alcohol, certain medications, and herbal supplements before the trial.

Inclusion Criteria

I am prescribed cisplatin at a dose higher than 25 mg/m^2.

No history of alcohol consumption of >14 drinks/week

Willingness to comply with study

Exclusion Criteria

I have a severe stomach or bowel condition causing fluid loss.

I am not taking drugs like metformin or antivirals that affect drug transport in the body.

I have been diagnosed with kidney cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cisplatin and are evaluated for kidney toxicity with antiemetic regimens

3 days

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Granisetron
• Ondansetron
• Palonosetron

Trial Overview The study tests if nausea drugs like Palonosetron, Granisetron, Ondansetron affect kidney damage from cisplatin therapy. It also examines how cisplatin levels in the body and genetic factors contribute to kidney injury risk.

Participant Groups

Group I: Palonosetron Experimental Treatment 1 Intervention

Participants randomized to an antiemetic regimen containing palonosetron 0.25 mg IV and evaluated for cisplatin toxicity after the first dose of cisplatin.

Group II: Ondansetron Experimental Treatment 1 Intervention

Participants randomized to an antiemetic regimen containing ondansetron 8 mg oral or IV and evaluated for cisplatin toxicity after the first dose of cisplatin.

Group III: Granisetron Experimental Treatment 1 Intervention

Participants randomized to an antiemetic regimen containing granisetron 2 mg oral or IV and evaluated for cisplatin toxicity after the first dose of cisplatin.

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

National Institute of General Medical Sciences (NIGMS)

Collaborator

Trials

315

Recruited

251,000+

Memorial Sloan Kettering Cancer Center

Collaborator

Trials

1,998

Recruited

602,000+

Rutgers University

Collaborator

Trials

127

Recruited

2,814,000+

Findings from Research

5-HT3 receptor antagonists, such as ondansetron, granisetron, and dolasetron, are effective in preventing nausea and vomiting in cancer patients undergoing moderately- and highly-emetogenic chemotherapy, both in intravenous and oral forms.

There are no significant differences in efficacy among the three 5-HT3 receptor antagonists, making them clinically equivalent, and the choice of which to use should consider cost and the specific chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in use of the 5-HT3 receptor antagonists. Walton, SM.[2019]

In a study of 1,085 chemotherapy-naive patients, a single oral dose of granisetron (2 mg) provided equivalent antiemetic control compared to intravenous ondansetron (32 mg) during the first 48 hours after chemotherapy.

Both medications were well tolerated, but ondansetron was associated with a higher incidence of dizziness and abnormal vision, suggesting that granisetron may be a safer option for some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of single-dose oral granisetron versus intravenous ondansetron in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy: a multicenter, double-blind, randomized parallel study. Perez, EA., Hesketh, P., Sandbach, J., et al.[2022]

In a study involving 987 chemotherapy-naive patients receiving cisplatin, single doses of granisetron (10 or 40 micrograms/kg) were found to be as effective as three doses of ondansetron (0.15 mg/kg) in preventing chemotherapy-induced nausea and vomiting.

All treatment regimens were well-tolerated, indicating that both granisetron and ondansetron are safe options for managing emesis in patients undergoing chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative clinical trial of granisetron and ondansetron in the prophylaxis of cisplatin-induced emesis. The Granisetron Study Group. Navari, R., Gandara, D., Hesketh, P., et al.[2017]

In a study of 97 pediatric outpatients, a dose of 40 micrograms.kg-1 of granisetron significantly reduced the incidence and frequency of postoperative nausea and vomiting (PONV) compared to a placebo and a lower dose of 10 micrograms.kg-1.

While effective, administering the higher dose of granisetron to prevent PONV in high-risk patients would incur an additional cost of approximately $99 to $101 per patient, indicating a trade-off between efficacy and financial impact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The dose-response relation and cost-effectiveness of granisetron for the prophylaxis of pediatric postoperative emesis. Cieslak, GD., Watcha, MF., Phillips, MB., et al.[2019]

References

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

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4. Germany pubmed.ncbi.nlm.nih.gov

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Early, empiric high-dose leucovorin rescue in lymphoma patients treated with sequential doses of high-dose methotrexate. [2021]

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Methotrexate overdose in clinical practice. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Advances in use of the 5-HT3 receptor antagonists. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Comparison of single-dose oral granisetron versus intravenous ondansetron in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy: a multicenter, double-blind, randomized parallel study. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Comparative clinical trial of granisetron and ondansetron in the prophylaxis of cisplatin-induced emesis. The Granisetron Study Group. [2017]

13. India pubmed.ncbi.nlm.nih.gov

Comparison of Palonosetron with Granisetron for Prevention of Postoperative Nausea and Vomiting in Patients Undergoing Laparoscopic Abdominal Surgery. [2022]

14. United States pubmed.ncbi.nlm.nih.gov

The dose-response relation and cost-effectiveness of granisetron for the prophylaxis of pediatric postoperative emesis. [2019]