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

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ClinicalTrials.gov Identifier: NCT01759862
Recruitment Status : Unknown
Verified June 2014 by Stanford University.
Recruitment status was:  Recruiting
First Posted : January 3, 2013
Last Update Posted : July 1, 2014
Sponsor:
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment
Function of Renal Transplant Drug: Aminophylline Other: Theophylline drug levels Drug: Placebo

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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.


Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Perioperative Aminophylline to Improve High Risk Renal Graft Outcome- a Double Blinded, Placebo Controlled, Randomized Clinical Trial
Study Start Date : November 2012
Estimated Primary Completion Date : June 2016
Estimated Study Completion Date : December 2016

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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.

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.
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.

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


Outcome Measures

Primary Outcome Measures :
  1. Calculated estimated Glomerular Filtration rate (eGFR) [ Time Frame: 5 days ]
    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.


Secondary Outcome Measures :
  1. Urinary NGAL (Neutrophil gelatinase-associated lipocalin) levels [ Time Frame: 12 hours post transplant ]
    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.


Other Outcome Measures:
  1. Degree of fibrosis measured on protocol biopsy [ Time Frame: 6 months ]
    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.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01759862


Locations
United States, California
Lucile Packard Children's Hospital at Stanford Recruiting
Stanford, California, United States, 94305-5208
Contact: Vivian Shih, MD    650-723-7903    wvshih@stanford.edu   
Contact: Paul C Grimm, MD    6507237903    pgrimm@stanford.edu   
Principal Investigator: Vivian Shih, MD         
Sub-Investigator: Paul Grimm, MD         
Sponsors and Collaborators
Stanford University
Investigators
Study Director: Paul C Grimm, MD Medical director, Pediatric Kidney Transplant Program Department of Pediatric Nephrology , Lucile Packard Children's hospital
More Information

Publications:
Responsible Party: Stanford University
ClinicalTrials.gov Identifier: NCT01759862     History of Changes
Other Study ID Numbers: 24280
First Posted: January 3, 2013    Key Record Dates
Last Update Posted: July 1, 2014
Last Verified: June 2014

Keywords provided by Stanford University:
kidney transplant
Aminophylline
pediatric

Additional relevant MeSH terms:
Theophylline
Aminophylline
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Cardiotonic Agents
Protective Agents