Clinical trial NCT06196853: Prevention of Cisplatin-induced Nephrotoxicity
Official title: Nephroprotective Effects of Aminophylline in Pediatric Oncologic Patient on Cisplatin Based Chemotherapy; Double Blind Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Acute Kidney Injury
Renal Tubulopathy
Keywords: Acute Kidney Injury
Chemotherapy induced kidney related complication
Lead sponsor: Mahidol University
Sponsor class: OTHER
First posted: 2024-01-09
Enrollment: 24
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The research design is a prospective, randomized, controlled clinical trial in children to study effect of aminophylline in preserving renal function in oncologic patient received cisplatin either combined with other CMT or used alone. The participants in both groups will receive standard protocol pre-cisplatin infusion which include hydration with 5%DNSS/2 with KCL and MgSO4 IV infusion. In the treatment group, the participants will receive aminophylline infusion in the first 24 hours along with cisplatin, followed by oral aminophylline oral three times daily orally for 4 consecutive days post cisplatin. The aminophylline serum level will be maintained at the therapeutic range 10-20 mg. The side effect of aminophylline including nausea, vomiting and ECG will be monitored. The collected data including urine volume, GFR (estimated by cystatin C-creatinine based equation and by radiopharmaceutical-Tc DTPA), and renal tubular biomarker (urine B2 macroglobulin and urine NGAL) will be collected at baseline before receiving cisplatin, 24 hours and 5 days post cisplatin.


Eligibility criteria: Inclusion Criteria:

* Age under 18 years old
* Oncology patients who receive cisplatin-based therapy

Exclusion Criteria:

* Preexisting renal anomalies
* Preexisting GFR less than 60 ml/min/1.73 m2
* Contraindication of aminophylline including structural heart disease, arrhythmia, hyperthyroidism, chronic liver disease, epilepsy
* Aminophylline use within 24 hours prior to study entry

Primary outcomes:
measure: creatinine and cystatin C-based glomerular filtration rate estimation
timeFrame: Baseline before cisplatin, and 24 hours and 5 days post cisplatin
measure: Radionuclide-based glomerular filtration rate measurement
timeFrame: Baseline before cisplatin and 5 days post cisplatin
Secondary outcomes:
measure: Renal tubular biomarkers
timeFrame: Baseline before cisplatin, and 24 hours and 5 days post cisplatin
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: Siriraj hospital, Mahidol university
Study officials:
affiliation: Siriraj Hospital
name: Anirut Pattaragarn, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: McSweeney KR, Gadanec LK, Qaradakhi T, Ali BA, Zulli A, Apostolopoulos V. Mechanisms of Cisplatin-Induced Acute Kidney Injury: Pathological Mechanisms, Pharmacological Interventions, and Genetic Mitigations. Cancers (Basel). 2021 Mar 29;13(7):1572. doi: 10.3390/cancers13071572.
citation: Sugawara M, Mochizuki T, Takekuma Y, Miyazaki K. Structure-affinity relationship in the interactions of human organic anion transporter 1 with caffeine, theophylline, theobromine and their metabolites. Biochim Biophys Acta. 2005 Aug 15;1714(2):85-92. doi: 10.1016/j.bbamem.2005.06.006.
citation: Alsaadoun S, Rustom F, Hassan HA, Alkhurais H, Aloufi M, Alzahrani S, Bakhsh S, Dalbhi SA. Aminophylline for improving acute kidney injury in pediatric patients: A systematic review and meta-analysis. Int J Health Sci (Qassim). 2020 Nov-Dec;14(6):44-51.
citation: Benoehr P, Krueth P, Bokemeyer C, Grenz A, Osswald H, Hartmann JT. Nephroprotection by theophylline in patients with cisplatin chemotherapy: a randomized, single-blinded, placebo-controlled trial. J Am Soc Nephrol. 2005 Feb;16(2):452-8. doi: 10.1681/ASN.2004030225. Epub 2004 Dec 8.