Pharmacokinetics of Zoledronic Acid in Patients on Dialysis

Официальное название

Pharmacokinetics of Zoledronic Acid in Patients With Chronic Kidney Disease on Dialysis

Обзор

Osteoporosis is a frequent complication of chronic kidney disease (CKD) on dialysis, with an estimated prevalence of approximately 40%. It is associated with increased fracture risk, reduced quality of life, and higher mortality. Despite available therapies, management often remains suboptimal, partly due to limited evidence on the safety and pharmacokinetics of bisphosphonates in this population. Objectives: To understand the pharmacokinetics of zoledronic acid in CKD patients on dialysis, as well as to analyze its effects on biomarkers of bone metabolism, bone mineral density (BMD), and clinical outcomes. Materials and Methods: This prospective clinical study involves 24 adult individuals, 8 with CKD-associated osteoporosis (control group; estimated glomerular filtration rate (eGFR) ≥ 35 mL/min/1.73 m²) and 16 with CKD-associated osteoporosis anuric on dialysis patients. Individuals undergoing dialysis will be assigned to receive zoledronic acid at doses of 2.5 mg or 5 mg intravenously (single dose, at the beggining of dialysis session), while patients with CKD-associated osteoporosis (control group; estimated glomerular filtration rate (eGFR) ≥ 35 mL/min/1.73 m²) will receive 5 mg, also in a single dose. Serial blood samples will be collected after infusion, during dialysis session and again up to 96h after dialysis session initiation. The dialysate will be continuously sampled in a tank and aliquots collected for further analysis. The plasma levels of zoledronic acid will be calculated from blood and dialysate samples using liquid chromatography mass spectrometry. The primary outcome is the plasma concentration-time curve of zoledronic acid during a regular dialysis session. Secondary outcomes are: (i) plasma concentration of zoledronic acid up to 96h;(ii) the total mass of zoledronic acid extracted by the dialysate; (iii) the dialytic clearance of zoledronic acid. Evaluation of bone biomarkers (e.g., PTH, alkaline phosphatase, calcium, phosphorus, CTX, and P1NP) and BMD (assessed by bone densitometry) will be performed at baseline and at 12 months. The study will be conducted at the UNICAMP Clinical Hospital, with the participation of one participating center, subject to prior approval from the respective Research Ethics Committees. All participants will be included only after signing the Informed Consent Form. Data will be anonymized and processed in accordance with the General Data Protection Law (LGPD). Expected results: To characterize the pharmacokinetic profile and establish the best dosage regimen of zoledronic acid in patients with CKD on dialysis; to observe the impact of the drug on biomarkers of bone metabolism and BMD.

Вмешательства

• Препарат Zoledronic Acid Injection, 5.0 mg, single dose
  Zoledronic Acid Injection, 5.0 mg, single dose for patients with CKD-associated osteoporosis with eGFR \>= 35 mL/min.
• Препарат Zoledronic Acid Injection, 2.5 mg, single dose
  Zoledronic Acid Injection, 2.5 mg, single dose, for patients with CKD-associated osteoporosis on dialysis, at the beginning of dialysis session.
• Препарат Zoledronic Acid Injection, 5.0 mg, single dose
  Zoledronic Acid Injection, 5.0 mg, single dose, for patients with CKD-associated osteoporosis on dialysis, at the beginning of dialysis session.

Первичные конечные точки

• Area Under the Curve of zoledronic acid (ng.mL/mL) [Срок оценки: From the start of dialysis session to ninety six hours (96 hours) post- drug administration.]

Вторичные конечные точки (1)

• Total mass of dapagliflozin extracted by the dialysis [Срок оценки: From the dialysis session start to the end of session at four hours (4h)]

Критерии участия

Критерии включения

• Individuals aged 18 years or older, with CKD-associated osteoporosis
• eGFR ≥ 35 mL/min/1.73 m2 and advanced CKD on dialysis
• Agree to participate in the research by signing the informed consent form

Критерии исключения

• Individuals under 18 years of age, pregnant or breastfeeding women
• Patients with CKD with hypocalcemia/hypophsphatemia
• Patients with CKD on dialysis with residual diuresis\*
• Patients with CKD on low-flux membrane dialysis\*
• Patients with neoplasia
• Hypersensitivity to bisphosphonates, or previous use of the medication
• Inadequate oral condition or anticipated invasive dental procedure within the next 12 months
• Alkaline phosphatase < 98 IU/L or > 180 IU/L\*
• PTH < 130 pg/mL and > 585 pg/mL\*
• Severe liver disease
• Severe heart disease
• Clinical suspiction of osteomalacia
• Cytopenias, defined as: platelets < 120,000/mm³, neutrophils < 3,000/mm³, lymphocytes < 1,000/mm³ and hematocrit < 26% \* Applicable only to the group of patients undergoing dialysis.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Бразилия · 1 центр

• School of Medical Sciences, University of Campinas — Campinas

Идентификаторы

NCT: NCT07741136 · 97356426.2.1001.5404

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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