Clinical trial NCT01759862
Conditions: Function of Renal Transplant
Keywords: kidney transplant Aminophylline pediatric
Sponsor: Stanford University
Start date: 2012-11-01; Completion date: 2017-07-25
Enrollment: 50 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The aim of this study is to evaluate whether peri-transplant administration of a drug named aminophylline to children undergoing a kidney transplant from deceased donors improves early graft function and also projects on long term graft function.

Detailed description:
This is a Double-blinded, placebo-controlled, randomized, clinical trial to evaluate whether administration of aminophylline starting pretransplant until post-transplant day 5 improves early kidney function and projects also on long term graft function.

Study Arms and intervention: On admit to the hospital prior to transplant, patients will be randomized into treatment or control arms. The randomization will be based on age groups 1-5y, 5-12y and 12-18y Treatment arm: Patients will receive aminophylline loading dose 5mg/kg prior to transplant and will continue to receive aminophylline 1.8mg/kg Q6h for a total of 20 doses.

Control arm: Patients will receive placebo infusion of normal saline, pre-transplant, followed by normal saline infusions matched by volume and frequency to treatment arm for a total of 20doses.

The only difference between the two arms will be the study intervention. Other than that all patients will receive the same standard of care for patients undergoing a kidney transplant.

Theophylline drug levels will be monitored every morning from all patients for the first 4 days post- transplant. Theophylline levels will be reported independently by the laboratory in a faxed research report directly to the pharmacist who will perform dose adjustments, according to the following table.

Theophylline Level (mcg/ml) Dose Adjustment \<2 Increase subsequent doses by 50% 2-2.9 Increase subsequent doses by 33% 3-3.9 Increase subsequent doses by 25% 4-4.9 Increase subsequent doses by 15% 5-7 (goal) Target Level; No dose adjustment 7.1-8.4 Decrease subsequent doses by 10% 8.5-9.9 Decrease subsequent doses by 15% 10-12.4 Decrease subsequent doses by 25% 12.5-14.9 Decrease subsequent doses by 50% 15-19.9 Decrease subsequent doses by 67% \>19.9 Discontinue all aminophylline doses. Contact Medical Monitor

All involved personnel will be blinded to the patient's allocation and to the drug level results.

The investigators will also collect a urine sample for NGAL (Neutrophil gelatinase-associated lipocalin)levels from all patients at 12 hours post-transplant.

Primary outcome will be calculated Glomerular Filtration Rate(GFR) on postoperative day 5. The investigators will determine whether patients in the aminophylline group had improved GFR compared to control group.

The investigators will also determine whether patients who received aminophylline had lower urinary NGAL levels compared to control group indicating a lesser degree of kidney injury. Urinary NGAL (Neutrophil gelatinase-associated lipocalin) is a biomarker of kidney injury. Elevated urinary NGAL levels post-transplant were found to be predictive of delayed graft function and the need for dialysis post-transplant.

At the investigators' center all patients undergo routine kidney protocol biopsies at 6 months post- transplant. After the slides are read by the pathologist the investigators will use the same tissue blocks to quantify the amount of fibrosis using computerized image analysis of Sirius Red-stained biopsies. The amount of fibrosis seen on 6 months protocol biopsies was proven to be correlated with expected graft survival.

An independent medical monitor will be assigned to manage toxic theophylline levels \>20mcg/mL. The laboratory will report directly to the medical monitor, who will discontinue aminophylline and remove the patient from the study.

The trial will be also be monitored with a Data Safety Monitoring Board (DSMB) unrelated to the study. The DSMB will meet after enrollment of 20 patients to assess for drug safety and monitor for adverse events of the drug.

Arms: arm 1: Patients will receive aminophylline loading dose 5mg/kg prior to transplant and will continue to receive aminophylline 1.8mg/kg Q6h for a total of 20 doses.

Theophylline drug levels will be monitored daily for 4 days. arm 2: Patients will receive placebo infusion of normal saline, pre-transplant, followed by normal saline infusions matched by volume and frequency to treatment arm for a total of 20 doses.

Drug levels will be monitored daily for 4 days.
Interventions: intervention 1: Aminophylline intervention 2: Theophylline drug levels intervention 3: Placebo
Intervention descriptions: intervention 1: Aminophylline loading dose 5mg/kg prior to transplant and will continue to receive aminophylline 1.8mg/kg Q6h for a total of 20 doses. intervention 2: Theophylline drug levels will be monitored every morning from all patients for the first 4 days post- transplant. intervention 3: Patients will receive placebo infusion of normal saline, pre-transplant, followed by normal saline infusions matched by volume and frequency to treatment arm for a total of 20 doses.

Protocol documents: