Perioperative Aminophylline to Improve Early Kidney Function After a Kidney Transplant
Condition: Function of Renal Transplant
Study type: Interventional

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.
    

Intervention name(s): Aminophylline; Theophylline drug levels; Placebo
Intervention type(s): Drug; Other; Drug
Intervention description(s): 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 every morning from all patients for the first 4 days post- transplant.; 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.
Other intervention name(s): Theophylline; Normal saline
Intervention MeSH terms: Aminophylline; Theophylline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: kidney transplant; Aminophylline; pediatric