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

February 11, 2019 updated by: Orly Haskin, Stanford University

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Stanford, California, United States, 94305-5208
        • Lucile Packard Children's Hospital at Stanford

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 17 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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
  4. graft was placed on pump after harvesting

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • Normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
5 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Urinary NGAL (Neutrophil Gelatinase-associated Lipocalin)/ Creatinine Ratio
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. NGAL levels are corrected for urine creatinine.
12 hours post transplant

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Presence 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
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Investigators

  • Study Director: Paul C Grimm, MD, Medical director, Pediatric Kidney Transplant Program Department of Pediatric Nephrology , Lucile Packard Children's hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2012

Primary Completion (Actual)

January 5, 2017

Study Completion (Actual)

July 25, 2017

Study Registration Dates

First Submitted

December 30, 2012

First Submitted That Met QC Criteria

December 30, 2012

First Posted (Estimate)

January 3, 2013

Study Record Updates

Last Update Posted (Actual)

March 5, 2019

Last Update Submitted That Met QC Criteria

February 11, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 24280

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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