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

NCT ID: NCT01491919

Last Updated: 2015-07-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2013-09-30

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.

Conditions

Hypertension

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Low Dose: Lisinopril

Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day

Group Type: EXPERIMENTAL

Lisinopril

Intervention Type: DRUG

Subjects will be randomized to Low, Medium, or High dose of Lisinopril

Medium Dose: Lisinopril

Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day

Group Type: EXPERIMENTAL

Lisinopril

Intervention Type: DRUG

Subjects will be randomized to Low, Medium, or High dose of Lisinopril

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.

Group Type: EXPERIMENTAL

Lisinopril

Intervention Type: DRUG

Subjects will be randomized to Low, Medium, or High dose of Lisinopril

Interventions

Lisinopril

Subjects will be randomized to Low, Medium, or High dose of Lisinopril

Intervention Type: DRUG

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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

The Emmes Company, LLC

INDUSTRY

Sponsor Role: collaborator

University of Rochester

OTHER

Sponsor Role: collaborator

OpAns, LLC

UNKNOWN

Sponsor Role: collaborator

Uptal Patel

OTHER

Sponsor Role: lead

Responsible Party

Uptal Patel

Assoc Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Daniel Benjamin, MD, PhD, MPH

Role: STUDY_DIRECTOR

Duke University

Howard Trachtman, MD

Role: STUDY_CHAIR

NYU Langone Health

Uptal D Patel, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Adam Frymoyer, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

University of Alabama

Birmingham, Alabama, United States

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Emory University and Children's Healthcare of Atlanta

Atlanta, Georgia, United States

University of Michigan

Ann Arbor, Michigan, United States

Children's Mercy Hospitals & Clinics

Kansas City, Missouri, United States

New York University Langone Medical Center

New York, New York, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Countries

United States

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Related Links

http://bpca.nichd.nih.gov/clinical/network/index.cfm

Pediatric Trials Network (PTN)

http://www.nichd.nih.gov/

The Eunice Kennedy Shriver National Institute of Child Health and Human

http://www.nlm.nih.gov/medlineplus/druginfo/meds/a692051.html

Information about Lisinopril

Other Identifiers

HHSN275201000003I

Identifier Type: OTHER

Identifier Source: secondary_id

Pro00029537

Identifier Type: -

Identifier Source: org_study_id