Safety Study of Lisinopril in Children and Adolescents With a Kidney Transplant

Status:	Completed
Conditions:	High Blood Pressure (Hypertension)
Therapuetic Areas:	Cardiology / Vascular Diseases
Healthy:	No
Age Range:	2 - 17
Updated:	11/30/2013
Start Date:	June 2012
End Date:	February 2014

Safety and Pharmacokinetics of Lisinopril in Pediatric Kidney Transplant Recipients

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.

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 ACEI agents (e.g.,
enalapril, ramipril, quinapril)

2. History of anaphylaxis attributable to iohexol or an iodine hypersensitivity

3. Use of an 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 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

We found this trial at

sites

Arkansas Children's Hospital

1 Children's Way
Little Rock, Arkansas 72202

(501) 364-1100