Perioperative Aminophylline to Improve Early Kidney Function After a Kidney Transplant (RTphylline)

This study is currently recruiting participants.
Verified March 2013 by Stanford University
Sponsor:
Information provided by (Responsible Party):
Stanford University
ClinicalTrials.gov Identifier:
NCT01759862
First received: December 30, 2012
Last updated: March 19, 2013
Last verified: March 2013

December 30, 2012
March 19, 2013
November 2012
June 2014   (final data collection date for primary outcome measure)
Calculated estimated Glomerular Filtration rate (eGFR) [ Time Frame: 5 days ] [ Designated as safety issue: No ]
The investigators will measure blood creatinine on post-operative day 5 and using the Schwartz equation will calculate estimated glomerular filtration rate (GFR) to determine kidney function.
Calculated estimated Glomerular Filtration rate (eGFR) [ Time Frame: 5 days ] [ Designated as safety issue: No ]
We will measure blood creatinine on post-operative day 5 and using the Schwartz equation will calculate estimated glomerular filtration rate (GFR) to determine kidney function.
Complete list of historical versions of study NCT01759862 on ClinicalTrials.gov Archive Site
Urinary NGAL (Neutrophil gelatinase-associated lipocalin) levels [ Time Frame: 12 hours post transplant ] [ Designated as safety issue: No ]
urinary NGAL(Neutrophil gelatinase-associated lipocalin) is a biomarker for kidney injury. NGAL levels 12h post-transplant were found to be a marker for development of delayed graft function and need for dialysis post-transplant.
Same as current
Degree of fibrosis measured on protocol biopsy [ Time Frame: 6 months ] [ Designated as safety issue: No ]
The investigators will use the same cores that are obtained during routine 6 months protocol biopsies to quantify the amount of fibrosis using computerized image analysis of Sirius Red-stained biopsies. The degree of fibrosis at 6 months was found to correlate with graft survival.
Degree of fibrosis measured on protocol biopsy [ Time Frame: 6 months ] [ Designated as safety issue: No ]
We will use the same cores that are obtained during routine 6 months protocol biopsies to quantify the amount of fibrosis using computerized image analysis of Sirius Red-stained biopsies. The degree of fibrosis at 6 months was found to correlate with graft survival.
 
Perioperative Aminophylline to Improve Early Kidney Function After a Kidney Transplant
Perioperative Aminophylline to Improve High Risk Renal Graft Outcome- a Double Blinded, Placebo Controlled, Randomized Clinical Trial

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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Function of Renal Transplant
  • Drug: Aminophylline
    Aminophylline loading dose 5mg/kg prior to transplant and will continue to receive aminophylline 1.8mg/kg Q6h for a total of 20 doses.
    Other Name: Theophylline
  • Other: Theophylline drug levels
    Theophylline drug levels will be monitored every morning from all patients for the first 4 days post- transplant.
  • Drug: Placebo
    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 Name: Normal saline
  • Experimental: Aminophylline

    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.

    Interventions:
    • Drug: Aminophylline
    • Other: Theophylline drug levels
  • Placebo Comparator: Control

    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:
    • Other: Theophylline drug levels
    • Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
50
December 2014
June 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Pediatric kidney transplant recipients less than 21 years of age
  2. Patients undergoing deceased donor (DD) kidney transplants

Exclusion Criteria:

  1. Known history of non-sinus tachycardia
  2. Multiple organ transplants recipients
  3. Severe liver dysfunction
Both
1 Year to 21 Years
No
Not Provided
United States
 
NCT01759862
24280
Yes
Stanford University
Stanford University
Not Provided
Study Director: Paul C Grimm, MD Medical director, Pediatric Kidney Transplant Program Department of Pediatric Nephrology , Lucile Packard Children's hospital
Stanford University
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP