Safety Study of Lisinopril in Children and Adolescents With a Kidney Transplant
Condition: Hypertension
MeSH terms: Hypertension
Intervention: Lisinopril
Intervention description: Subjects will be randomized to Low, Medium, or High dose of Lisinopril
Intervention MeSH terms: Lisinopril
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 2 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: High Blood Pressure; Hypertension; Renal Transplantation; Kidney Transplantation

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