Clinical trial NCT01491919: Safety Study of Lisinopril in Children and Adolescents With a Kidney Transplant
Official title: Safety and Pharmacokinetics of Lisinopril in Pediatric Kidney Transplant Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypertension
Keywords: High Blood Pressure
Hypertension
Renal Transplantation
Kidney Transplantation
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: The Emmes Company, LLC
name: University of Rochester
name: OpAns, LLC
First posted: 2011-12-14
Enrollment: 26
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The drug lisinopril is approved by the U.S. Food and Drug Administration for the treatment of high blood pressure, heart failure, and acute heart attacks in adult patients. In children over 6 years of age, lisinopril is approved for the treatment of high blood pressure. Lisinopril is in a group of medications called angiotensin-converting enzyme inhibitors (ACE). ACE inhibitors such as lisinopril work by decreasing certain chemicals that tighten the blood vessels so blood flows more smoothly and the heart can pump blood more efficiently.

There is some information available about how children with high blood pressure absorb, distribute, metabolize, and eliminate lisinopril (this information about medication processing by the body is called pharmacokinetic data). However, there is no information about how children with high blood pressure who have received a kidney transplant process lisinopril. In addition to decreasing blood pressure, investigators believe that lisinopril may help kidney transplants work longer by reducing the activity of chemicals made by cells in kidney transplants that can lead to inflammation and injury. Such benefits have not been found with another group of blood pressure medications called calcium channel blockers, which are the most commonly used medication group to control high blood pressure in children after a kidney transplant. A clinical trial will be conducted in the future to compare which medication group helps kidney transplants in children last longer. To guide the selection of the best dose to test in future studies, investigators in this study will try to determine the safety profile, dose tolerability, and pharmacokinetics of lisinopril in children and adolescents (2-17 years of age) who have received a kidney transplant and have high blood pressure.


Eligibility criteria: Inclusion Criteria:

1. Kidney transplant recipient
2. Age 2-17 years, inclusive, at the time of first study dose
3. Estimated GFR (eGFR) ≥30 ml/min/1.73m2, with stable allograft function as indicated by \<20% change in serum creatinine in the previous 30 days
4. Stable immunosuppressive regimen, as indicated by \<10% change in dosage (in mg/kg) in these medications, within the 14 days prior to enrollment
5. Systolic BP \>90th percentile for age, gender, and height, necessitating initiation or addition of an antihypertensive medication
6. For females of child-bearing potential, a negative serum pregnancy test prior to initial dosing and agreement to practice appropriate contraceptive measures, including abstinence, from the time of the initial pregnancy testing through the remainder of the study (30 days after last administration of investigational agents).

Exclusion Criteria:

1. History of anaphylaxis attributable to lisinopril or other angiotensin-converting enzyme inhibitor (ACEI) agents (e.g.,enalapril, ramipril, quinapril)
2. History of anaphylaxis attributable to iohexol or an iodine hypersensitivity
3. Use of an angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker, or renin antagonist within 30 days prior to enrollment
4. Stage 2 hypertension defined as the \>99th percentile for age, height and gender + 5 mm Hg
5. Blood Potassium value \> 6.0 milliequivalent / liter (mEq/L) (as determined at the screening visit)
6. Previous participation in this study
7. Physician concern that the participant may not adhere to the study protocol, based on prior behavior
8. Current plasmapheresis treatment
9. History of angioedema
10. Pregnancy

Primary outcomes:
measure: Pharmacokinetics (PK) - Area Under the Plasma Concentration-time Curve (AUC)
timeFrame: Day 14 (+/- 3 days) of lisinopril therapy at hours 0 (pre-dose) and 1,2,4,5,8,12 and 24 hrs after dose
measure: PK - Maximum Observed Concentration of Drug in Plasma (Cmax)
timeFrame: Day14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after dose
measure: PK - Time of the Maximum Observed Concentration in Plasma (Tmax)
timeFrame: Day 14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after dose
measure: PK - Oral Clearance (CL/F)
timeFrame: Day 14 (+/- 3 d) of dose at 0 hour and at 1, 2, 4, 5, 8, 12, and 24 hrs after dose
measure: PK Renal Clearance (CLrenal)
timeFrame: Day 14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after dose.
measure: Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) During/After Study Drug Administration
timeFrame: First dose of study drug to 30 days after final study visit for AEs and until resolution for SAEs
Secondary outcomes:
measure: Change in Potassium Level From Baseline in Lisinopril-naive Participants
timeFrame: At baseline visit and Day 14 prior to final study dose.
measure: Worse Post-dose Decrease in Estimated Glomerular Filtration Rate (eGFR) From Baseline in Lisinopril-naive Participants
timeFrame: Baseline to Day 14 (+/- 3 days)
measure: Largest eGFR Percent Decrease From Baseline in Lisinopril-naive Participants
timeFrame: Baseline to Day 14 (+/- 3 days)
measure: Change in Urine Protein/Creatinine From Baseline in Lisinopril-naive Participants.
timeFrame: Baseline to worst post-dose before Day 14 (+/- 3 days)
measure: Change in Diastolic Blood Pressure From Baseline in Lisinopril-naive Participants
timeFrame: Baseline to Day 14 (+/-3 days)
measure: Change in Systolic Blood Pressure From Baseline in Lisinopril-naive Participants
timeFrame: Baseline to Day 14 (+/- 3 days)
measure: Change in Systolic Blood Pressure (BP) From Baseline in Lisinopril SOC Group
timeFrame: Screening to Day 14 to 40
measure: Change in Diastolic Blood Pressure From Baseline in Lisinopril SOC Group
timeFrame: Screening to Day 14 to 40
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Atlanta
country: United States
facility: Emory University and Children's Healthcare of Atlanta
state: Georgia
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Kansas City
country: United States
facility: Children's Mercy Hospitals & Clinics
state: Missouri
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Duke University
name: Daniel Benjamin, MD, PhD, MPH
role: STUDY_DIRECTOR
affiliation: NYU Langone Health
name: Howard Trachtman, MD
role: STUDY_CHAIR
affiliation: Duke University
name: Uptal D Patel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Adam Frymoyer, MD
role: PRINCIPAL_INVESTIGATOR
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