Trial Outcomes & Findings for Perioperative Aminophylline to Improve Early Kidney Function After a Kidney Transplant (NCT NCT01759862)

NCT ID: NCT01759862

Last Updated: 2019-03-05

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 50 participants
• Primary outcome timeframe: 5 days
• Results posted on: 2019-03-05

Participant Flow

Participant milestones

Measure	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. Target theophylline level is 5-7mcg/ml. Aminophylline dosing will be adjusted in order to achieve desired levels as stated in the study protocol.	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.
Overall Study STARTED	23	27
Overall Study COMPLETED	20	25
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Measure	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. Target theophylline level is 5-7mcg/ml. Aminophylline dosing will be adjusted in order to achieve desired levels as stated in the study protocol.	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.
Overall Study Physician Decision	3	1
Overall Study Adverse Event	0	1

Baseline Characteristics

Perioperative Aminophylline to Improve Early Kidney Function After a Kidney Transplant

Baseline characteristics by cohort

Measure	Aminophylline n=23 Participants 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. 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. Theophylline drug levels: Theophylline drug levels will be monitored every morning from all patients for the first 4 days post- transplant.	Control n=27 Participants 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. Theophylline drug levels: Theophylline drug levels will be monitored every morning from all patients for the first 4 days post- transplant. 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.	Total n=50 Participants Total of all reporting groups
Age, Continuous	11.28 years STANDARD_DEVIATION 4.8 • n=5 Participants	11.91 years STANDARD_DEVIATION 5.4 • n=7 Participants	11.62 years STANDARD_DEVIATION 5.1 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	12 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	15 Participants n=7 Participants	28 Participants n=5 Participants
Region of Enrollment United States	23 participants n=5 Participants	27 participants n=7 Participants	50 participants n=5 Participants

PRIMARY outcome

Timeframe: 5 days

Population: Intention to treat analysis

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.

Outcome measures

Measure	Aminophylline n=23 Participants 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. Target theophylline level is 5-7mcg/ml. Aminophylline dosing will be adjusted in order to achieve desired levels as stated in the study protocol.	Control n=27 Participants 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.
Calculated Estimated Glomerular Filtration Rate (eGFR)	67.39 ml/min/1.73m2 Standard Deviation 38.9	80.48 ml/min/1.73m2 Standard Deviation 52.1

SECONDARY outcome

Timeframe: 12 hours post transplant

Population: Participants with available data were included in the analysis.

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.

Outcome measures

Measure	Aminophylline n=21 Participants 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. Target theophylline level is 5-7mcg/ml. Aminophylline dosing will be adjusted in order to achieve desired levels as stated in the study protocol.	Control n=24 Participants 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.
Urinary NGAL (Neutrophil Gelatinase-associated Lipocalin)/ Creatinine Ratio	300.5 ng/mg Interval 105.5 to 1464.5	425.4 ng/mg Interval 140.3 to 1126.2

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 months

Population: Participants with available data were included in the analysis.

The investigators will use the same cores that are obtained during routine 6 months protocol biopsies to quantify the amount of fibrosis

Outcome measures

Measure	Aminophylline n=23 Participants 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. Target theophylline level is 5-7mcg/ml. Aminophylline dosing will be adjusted in order to achieve desired levels as stated in the study protocol.	Control n=26 Participants 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.
Presence of Fibrosis Measured on Protocol Biopsy	11 Participants	14 Participants

Adverse Events

Aminophylline

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Control

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Aminophylline n=23 participants at risk 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. Target theophylline level is 5-7mcg/ml. Aminophylline dosing will be adjusted in order to achieve desired levels as stated in the study protocol.	Control n=27 participants at risk 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.
Nervous system disorders Agitation	0.00% 0/23 • 6 months	7.4% 2/27 • 6 months
Cardiac disorders tachycardia at day 1 post transplant	30.4% 7/23 • 6 months	22.2% 6/27 • 6 months
Injury, poisoning and procedural complications tacrolimus toxicity	30.4% 7/23 • 6 months	37.0% 10/27 • 6 months
Renal and urinary disorders Acute kidney injury	0.00% 0/23 • 6 months	7.4% 2/27 • 6 months
Renal and urinary disorders Rejection	17.4% 4/23 • 6 months	22.2% 6/27 • 6 months

Additional Information

Paul Grimm

Stanford University

Phone: 6507237903

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place