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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Uptal Patel, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT01491919
First received: November 29, 2011
Last updated: December 18, 2013
Last verified: December 2013

November 29, 2011
December 18, 2013
June 2012
September 2013   (final data collection date for primary outcome measure)
Pharmacokinetics (PK) [ Time Frame: PK evaluations will be performed after 14 +/- 3 days of lisinopril therapy at 0 hour (pre-dose) 1, 2, 4, 5, 8, 12, and 24 hours post-lisinopril dose ] [ Designated as safety issue: No ]
  1. Area under the plasma concentration-time curve (AUC)
  2. Maximum observed concentration of drug in plasma (Cmax) and time of the maximum observed concentration in plasma (Tmax).
  3. Observed concentration prior to dose (C0h) and at the 24h post-dose pharmacokinetic sample (C24h).
  4. Apparent oral clearance (CL/F) and renal clearance (CLrenal).
Same as current
Complete list of historical versions of study NCT01491919 on ClinicalTrials.gov Archive Site
  • Safety [ Time Frame: First dose of lisinopril to 30 days after last dose of study medication ] [ Designated as safety issue: Yes ]
    1. Additional PK data: lisinopril absorption rate (ka), oral apparent volume of distribution (V/F), influence on PK by demographic/ clinical covariates
    2. AEs during/after study drug administration by organ system
    3. Additional BP data: control per protocol clinic BPs, 24h ABPM, need for additional BP medications
    4. Exposure-response relationship: lisinopril plasma concentrations and BP (PK-PD model)
    5. Estimated glomerular filtration rate (eGFR) change
    6. Change in urinary protein excretion
  • Non-Safety Secondary Outcome [ Time Frame: Dried Blood Spot (DBS) samples will be collected after 14 +/- 3 days of lisinopril therapy at 0 hour (pre-dose) and at 1, 2, 4, 5, 8, 12 and 24 hours post-lisinopril dose ] [ Designated as safety issue: No ]
    Dried blood spot (DBS) sampling validity
  • Non-Safety Secondary Outcome [ Time Frame: Iohexol GFR samples will be collected after 14 +/- 3 days of lisinopril therapy at intervals of 0, 2, 4, and 5 hours post-iohexol infusion ] [ Designated as safety issue: No ]
    eGFR and iohexol GFR relationship
  • Safety [ Time Frame: First dose of lisinopril to 30 days after last dose of study medication ] [ Designated as safety issue: Yes ]
    1. Additional PK data: lisinopril absorption rate (ka), oral apparent volume of distribution (V/F), influence on PK by demographic/ clinical covariates
    2. AEs during/after study drug administration by organ system
    3. Additional BP data: control per protocol clinic BPs, 24h ABPM, need for additional BP medications
    4. Exposure-response relationship: lisinopril plasma concentrations and BP (PK-PD model)
    5. Estimated glomerular filtration rate (eGFR) change
  • Non-Safety Secondary Outcome [ Time Frame: Dried Blood Spot (DBS) samples will be collected after 14 +/- 3 days of lisinopril therapy at 0 hour (pre-dose) and at 1, 2, 4, 5, 8, 12 and 24 hours post-lisinopril dose ] [ Designated as safety issue: No ]
    Dried blood spot (DBS) sampling validity
  • Non-Safety Secondary Outcome [ Time Frame: Iohexol GFR samples will be collected after 14 +/- 3 days of lisinopril therapy at intervals of 0, 2, 4, and 5 hours post-iohexol infusion ] [ Designated as safety issue: No ]
    eGFR and iohexol GFR relationship
Not Provided
Not Provided
 
Safety Study of Lisinopril in Children and Adolescents With a Kidney Transplant
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.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Hypertension
Drug: Lisinopril
Lisinopril will be administered as a single oral dose at the following three dose levels: 0.1, 0.2, and 0.4 milligram per kilogram. The medication will be taken orally in suspension or tablet formulation once a day. Participants will receive study medication for 14±3 days.
  • Experimental: Low Dose: Lisinopril
    Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
    Intervention: Drug: Lisinopril
  • Experimental: Medium Dose: Lisinopril
    Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
    Intervention: Drug: Lisinopril
  • Experimental: High Dose: Lisinopril
    Participants will initially receive study medication at 0.2 mg/kg/day for 5±2 days. If blood tests exclude drug-related toxicity, then the lisinopril dose will be increased to 0.4 mg/kg/day and participants will continue to complete the 14±3 day Treatment Period.
    Intervention: Drug: Lisinopril

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
26
September 2013
September 2013   (final data collection date for primary outcome measure)

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
Both
2 Years to 17 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01491919
Pro00029537, HHSN275201000003I
Yes
Uptal Patel, Duke University Medical Center
Uptal Patel
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study Director: Daniel Benjamin, MD, PhD, MPH Duke University
Study Chair: Howard Trachtman, MD Cohen Children's Medical Center of New York
Principal Investigator: Uptal D Patel, MD Duke University
Duke University
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP