HypertensionPhase 1PTN_LISINONCT01491919

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

A Phase 1 study testing Lisinopril in people with Hypertension, run by Uptal Patel at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 2 to 17 years
Conditions the study is for: Hypertension
What is being tested?: Lisinopril
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 26 participants
Where: 7 sitesUnited States
Study dates: Jun 2012to Sep 2013
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 2 to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

Kidney transplant recipient
Age 2-17 years, inclusive, at the time of first study dose
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
Stable immunosuppressive regimen, as indicated by <10% change in dosage (in mg/kg) in these medications, within the 14 days prior to enrollment
Systolic BP >90th percentile for age, gender, and height, necessitating initiation or addition of an antihypertensive medication
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).

Who cannot join

History of anaphylaxis attributable to lisinopril or other angiotensin-converting enzyme inhibitor (ACEI) agents (e.g.,enalapril, ramipril, quinapril)
History of anaphylaxis attributable to iohexol or an iodine hypersensitivity
Use of an angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker, or renin antagonist within 30 days prior to enrollment
Stage 2 hypertension defined as the >99th percentile for age, height and gender + 5 mm Hg
Blood Potassium value > 6.0 milliequivalent / liter (mEq/L) (as determined at the screening visit)
Previous participation in this study

Show all 10Show fewer

Physician concern that the participant may not adhere to the study protocol, based on prior behavior
Current plasmapheresis treatment
History of angioedema
Pregnancy

Trial locations and contacts

7 sites in 1 country.

City, postcode or hospital

7 sites in 1 country

United States7 sites

University of Michigan
Ann Arbor, Michigan, 48109
Emory University and Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
University of Alabama
Birmingham, Alabama, 35233
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Children's Mercy Hospitals & Clinics
Kansas City, Missouri, 64108
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
New York University Langone Medical Center
New York, New York, 10016

Other trials in United States

About this study

Official title: 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.

Conditions: Hypertension
Being tested: Lisinopril
Keywords: High Blood Pressure, Hypertension, Renal Transplantation, Kidney Transplantation
Medical subject headings: Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT01491919
Study group	Role	What they receive
Low Dose: Lisinopril	Experimental	Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day Receives: Drug: Lisinopril
Medium Dose: Lisinopril	Experimental	Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day Receives: Drug: Lisinopril
High Dose: Lisinopril	Experimental	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. Receives: Drug: Lisinopril

What is being measured

The primary outcome is the main question the study is designed to answer.

Pharmacokinetics (PK) - Area Under the Plasma Concentration-time Curve (AUC)
At the Day 14 (±3 days) visit, blood (1 mL) will be collected at 0 hour (pre-dose) and at 1, 2, 4, 5, 8, 12 and 24 hours post-lisinopril dose for determination of AUC. Geometric mean was calculated from all measurements.
Measured: Day 14 (+/- 3 days) of lisinopril therapy at hours 0 (pre-dose) and 1,2,4,5,8,12 and 24 hrs after dose
PK - Maximum Observed Concentration of Drug in Plasma (Cmax)
At the Day 14 (±3 days) visit, blood (1 mL) will be collected at 0 hour (pre-dose) and at 1, 2, 4, 5, 8, 12 and 24 hours post-lisinopril dose for determination of Cmax. Geometric mean was calculated from all measurements.
Measured: Day14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after dose
PK - Time of the Maximum Observed Concentration in Plasma (Tmax)
At the Day 14 (±3 days) visit, blood (1 mL) will be collected at 0 hour (pre-dose) and at 1, 2, 4, 5, 8, 12 and 24 hours post-lisinopril dose for determination of plasma lisinopril concentration. Medium was calculated from all measurements.
Measured: Day 14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after dose
PK - Oral Clearance (CL/F)
At the Day 14 (±3 days) visit, blood (1 mL) will be collected at 0 hour (pre-dose) and at 1, 2, 4, 5, 8, 12 and 24 hours post-lisinopril dose for determination of CL/F. Geometric mean was calculated from all measurements.
Measured: Day 14 (+/- 3 d) of dose at 0 hour and at 1, 2, 4, 5, 8, 12, and 24 hrs after dose
PK Renal Clearance (CLrenal)
At the Day 14 (±3 days) visit, blood (1 mL) will be collected at 0 hour (pre-dose) and at 1, 2, 4, 5, 8, 12 and 24 hours post-lisinopril dose for determination of CLrenal. Geometric mean was calculated from all measurements.
Measured: Day 14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after dose.
Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) During/After Study Drug Administration
Number of Adverse Events (AEs) related and not related to study drug; number of Serious Adverse Events (SAEs) related and not related to study drug
Measured: First dose of study drug to 30 days after final study visit for AEs and until resolution for SAEs

Secondary outcomes (8)

Change in Potassium Level From Baseline in Lisinopril-naive Participants
Potassium values will be obtained at Baseline and Day 14 prior to the final dose of study drug. Mean calculated from the two measurements.
Measured: At baseline visit and Day 14 prior to final study dose.
Worse Post-dose Decrease in Estimated Glomerular Filtration Rate (eGFR) From Baseline in Lisinopril-naive Participants
The eGFR at entry will need to be ≥ 30 ml/min/1.73m^2 to minimize concerns about an acute angiotensin-converting enzyme inhibitors (ACE-I)-mediated reduction in kidney function. eGFR ratio was computed from the worst post-dose value divided by the Baseline value.
Measured: Baseline to Day 14 (+/- 3 days)
Largest eGFR Percent Decrease From Baseline in Lisinopril-naive Participants
The eGFR at entry will need to be ≥ 30 ml/min/1.73m^2 to minimize concerns about an acute angiotensin-converting enzyme inhibitor (ACEI) mediated reduction in kidney function.
Largest eGFR percent decrease from baseline reported in results section.
Measured: Baseline to Day 14 (+/- 3 days)
Change in Urine Protein/Creatinine From Baseline in Lisinopril-naive Participants.
Change in urine protein/creatinine obtained as follows: Mean change (worst post-dose from baseline) presented for urine protein/creatinine ratio. Geometric mean of the ratio (worst post-dose / baseline with Geometric Coefficient of Variation percent (CV%) and greatest decrease presented for eGFR by dose group. Two patients in the high dose group had an evaluable urine protein/creatinine change.
Measured: Baseline to worst post-dose before Day 14 (+/- 3 days)
Change in Diastolic Blood Pressure From Baseline in Lisinopril-naive Participants
Ambulatory blood pressure readings were measured during the baseline/pre-study dose period using a SpaceLabs (Redmond, WA) device at home to avoid the confounding effects of venipuncture and abnormal sleep pattern.
Another blood pressure reading was performed at 1 day before the final dose of lisinopril (day before the last scheduled visit).
The mean of these measurements was calculated.
Measured: Baseline to Day 14 (+/-3 days)
Change in Systolic Blood Pressure From Baseline in Lisinopril-naive Participants
Ambulatory blood pressure readings were measured during the baseline/pre-study dose period using a SpaceLabs (Redmond, WA) device at home to avoid the confounding effects of venipuncture and abnormal sleep pattern.
Another blood pressure reading was performed at 1 day before the final dose of lisinopril (day before the last scheduled visit).
The mean from these measurements was calculated.
Measured: Baseline to Day 14 (+/- 3 days)
Change in Systolic Blood Pressure (BP) From Baseline in Lisinopril SOC Group
Lisinopril SOC participants were not given the ambulatory blood pressure machine to obtain readings at home, as was the Lisinopril-naive participants. Instead BP measurements were obtained during screening visit and compared to the Day 14 to 40 visit measurements. Note: these participants were not required to attend a Day 14 (+/-3 day visit) but did need to attend sometime between Day 14 to Day 40 (inclusive). The mean of these blood pressure measurements was calculated.
Measured: Screening to Day 14 to 40
Change in Diastolic Blood Pressure From Baseline in Lisinopril SOC Group
Lisinopril SOC participants were not given the ambulatory blood pressure machine to obtain readings at home, as was the Lisinopril-naive participants. Instead BP measurements were obtained during screening visit and compared to the Day 14 to 40 visit measurements (note: the participants were not required to attend a Day 14 (+/-3 day visit) but did need to attend sometime between Day 14 to Day 40. The mean from the blood pressure measurements was calculated.
Measured: Screening to Day 14 to 40

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2012Sep 2013

First posted14 Dec 2011 (estimated)
Study startJun 2012
Primary completionSep 2013
Study completionSep 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (34)Papers the sponsor has linked to this study.
Other trials for HypertensionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 26 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01491919
Sponsor's protocol ID: Pro00029537
Other IDs: HHSN275201000003I
Acronym: PTN_LISINO
Status last verified: Jun 2015
First submitted: 29 Nov 2011
Last updated: 8 Jul 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004 Aug;114(2 Suppl 4th Report):555-76. No abstract available.
PubMed 15286277
Knutter I, Wollesky C, Kottra G, Hahn MG, Fischer W, Zebisch K, Neubert RH, Daniel H, Brandsch M. Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited. J Pharmacol Exp Ther. 2008 Nov;327(2):432-41. doi: 10.1124/jpet.108.143339. Epub 2008 Aug 19.
PubMed 18713951
Lin JH, Chen IW, Ulm EH, Duggan DE. Differential renal handling of angiotensin-converting enzyme inhibitors enalaprilat and lisinopril in rats. Drug Metab Dispos. 1988 May-Jun;16(3):392-6.
PubMed 2900730
Hogg RJ, Delucchi A, Sakihara G, Wells TG, Tenney F, Batisky DL, Blumer JL, Vogt BA, Lo MW, Hand E, Panebianco D, Rippley R, Shaw W, Shahinfar S. A multicenter study of the pharmacokinetics of lisinopril in pediatric patients with hypertension. Pediatr Nephrol. 2007 May;22(5):695-701. doi: 10.1007/s00467-006-0399-5. Epub 2007 Jan 10.
PubMed 17216247
Prinivil® (lisinopril tablets) package insert; Whitehouse Station, NJ: Merck & Co., Inc.; 2003
Mitsnefes MM, Khoury PR, McEnery PT. Early posttransplantation hypertension and poor long-term renal allograft survival in pediatric patients. J Pediatr. 2003 Jul;143(1):98-103. doi: 10.1016/S0022-3476(03)00209-9.
PubMed 12915832
Silverstein DM, Leblanc P, Hempe JM, Ramcharan T, Boudreaux JP. Tracking of blood pressure and its impact on graft function in pediatric renal transplant patients. Pediatr Transplant. 2007 Dec;11(8):860-7. doi: 10.1111/j.1399-3046.2007.00753.x.
PubMed 17976120
Mitsnefes MM, Omoloja A, McEnery PT. Short-term pediatric renal transplant survival: blood pressure and allograft function. Pediatr Transplant. 2001 Jun;5(3):160-5. doi: 10.1034/j.1399-3046.2001.t01-1-00051.x.
PubMed 11422817
Cross NB, Webster AC, Masson P, O'connell PJ, Craig JC. Antihypertensives for kidney transplant recipients: systematic review and meta-analysis of randomized controlled trials. Transplantation. 2009 Jul 15;88(1):7-18. doi: 10.1097/TP.0b013e3181a9e960.
PubMed 19584673
Sorof JM, Goldstein SL, Brewer ED, Steiger HM, Portman RJ. Use of anti-hypertensive medications and post-transplant renal allograft function in children. Pediatr Transplant. 2000 Feb;4(1):21-7. doi: 10.1034/j.1399-3046.2000.00082.x.
PubMed 10731054
Hernandez AA, Moreso F, Bayes B, Lauzurica R, Sanz-Guajardo D, Gomez-Huertas E, Pereira P, Paul J, Crespo J, Amenabar JJ, Oliver J, Seron D. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in renal transplantation between 1990 and 2002 in Spain. NDT Plus. 2010 Jun;3(Suppl_2):ii21-ii25. doi: 10.1093/ndtplus/sfq068.
PubMed 20508862
Mitterbauer C, Heinze G, Kainz A, Kramar R, Horl WH, Oberbauer R. ACE-inhibitor or AT2-antagonist therapy of renal transplant recipients is associated with an increase in serum potassium concentrations. Nephrol Dial Transplant. 2008 May;23(5):1742-6. doi: 10.1093/ndt/gfm864. Epub 2008 Jan 30.
PubMed 18234845
Hiremath S, Fergusson D, Doucette S, Mulay AV, Knoll GA. Renin angiotensin system blockade in kidney transplantation: a systematic review of the evidence. Am J Transplant. 2007 Oct;7(10):2350-60. doi: 10.1111/j.1600-6143.2007.01928.x.
PubMed 17845569
Morath C, Schmied B, Mehrabi A, Weitz J, Schmidt J, Werner J, Buchler MW, Morcos M, Nawroth PP, Schwenger V, Doehler B, Opelz G, Zeier M. Angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers after renal transplantation. Clin Transplant. 2009 Dec;23 Suppl 21:33-6. doi: 10.1111/j.1399-0012.2009.01107.x.
PubMed 19930314
Inigo P, Campistol JM, Lario S, Piera C, Campos B, Bescos M, Oppenheimer F, Rivera F. Effects of losartan and amlodipine on intrarenal hemodynamics and TGF-beta(1) plasma levels in a crossover trial in renal transplant recipients. J Am Soc Nephrol. 2001 Apr;12(4):822-827. doi: 10.1681/ASN.V124822.
PubMed 11274244

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 8 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Safety and Pharmacokinetics of Lisinopril in Pediatric Kidney Transplant Recipients
ClinicalTrials.gov ID: NCT01491919
Acronym / sponsor ID: PTN_LISINO / Pro00029537
Conditions: Hypertension
Keywords: High Blood Pressure, Hypertension, Renal Transplantation, Kidney Transplantation
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 26 participants (actual)
Lead sponsor: Uptal PatelUniversity, hospital or other
Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), The Emmes Company, LLC, University of Rochester, OpAns, LLC
Study start: Jun 2012
Primary completion: Sep 2013 (actual)
Study completion: Sep 2013 (actual)
First posted: 14 Dec 2011 (estimated)
Results: Posted 8 Jul 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Low Dose: Lisinopril	Experimental	Drug: LisinoprilParticipants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
Medium Dose: Lisinopril	Experimental	Drug: LisinoprilParticipants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
High Dose: Lisinopril	Experimental	Drug: LisinoprilParticipants 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.

Who may qualify

Ages: 2 to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (6 listed)

Kidney transplant recipient
Age 2-17 years, inclusive, at the time of first study dose
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
Stable immunosuppressive regimen, as indicated by <10% change in dosage (in mg/kg) in these medications, within the 14 days prior to enrollment
Systolic BP >90th percentile for age, gender, and height, necessitating initiation or addition of an antihypertensive medication

Key exclusion criteria (10 listed)

History of anaphylaxis attributable to lisinopril or other angiotensin-converting enzyme inhibitor (ACEI) agents (e.g.,enalapril, ramipril, quinapril)
History of anaphylaxis attributable to iohexol or an iodine hypersensitivity
Use of an angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker, or renin antagonist within 30 days prior to enrollment
Stage 2 hypertension defined as the >99th percentile for age, height and gender + 5 mm Hg
Blood Potassium value > 6.0 milliequivalent / liter (mEq/L) (as determined at the screening visit)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LisinoprilSubjects will be randomized to Low, Medium, or High dose of Lisinopril	Drug	High Dose: Lisinopril, Low Dose: Lisinopril, Medium Dose: Lisinopril

Primary outcome

Pharmacokinetics (PK) - Area Under the Plasma Concentration-time Curve (AUC)
Time frame: Day 14 (+/- 3 days) of lisinopril therapy at hours 0 (pre-dose) and 1,2,4,5,8,12 and 24 hrs after dose
At the Day 14 (±3 days) visit, blood (1 mL) will be collected at 0 hour (pre-dose) and at 1, 2, 4, 5, 8, 12 and 24 hours post-lisinopril dose for determination of AUC. Geometric mean was calculated from all measurements.
PK - Maximum Observed Concentration of Drug in Plasma (Cmax)
Time frame: Day14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after dose
At the Day 14 (±3 days) visit, blood (1 mL) will be collected at 0 hour (pre-dose) and at 1, 2, 4, 5, 8, 12 and 24 hours post-lisinopril dose for determination of Cmax. Geometric mean was calculated from all measurements.
PK - Time of the Maximum Observed Concentration in Plasma (Tmax)
Time frame: Day 14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after dose
At the Day 14 (±3 days) visit, blood (1 mL) will be collected at 0 hour (pre-dose) and at 1, 2, 4, 5, 8, 12 and 24 hours post-lisinopril dose for determination of plasma lisinopril concentration. Medium was calculated from all measurements.
PK - Oral Clearance (CL/F)
Time frame: Day 14 (+/- 3 d) of dose at 0 hour and at 1, 2, 4, 5, 8, 12, and 24 hrs after dose
At the Day 14 (±3 days) visit, blood (1 mL) will be collected at 0 hour (pre-dose) and at 1, 2, 4, 5, 8, 12 and 24 hours post-lisinopril dose for determination of CL/F. Geometric mean was calculated from all measurements.
PK Renal Clearance (CLrenal)
Time frame: Day 14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after dose.
At the Day 14 (±3 days) visit, blood (1 mL) will be collected at 0 hour (pre-dose) and at 1, 2, 4, 5, 8, 12 and 24 hours post-lisinopril dose for determination of CLrenal. Geometric mean was calculated from all measurements.
Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) During/After Study Drug Administration
Time frame: First dose of study drug to 30 days after final study visit for AEs and until resolution for SAEs
Number of Adverse Events (AEs) related and not related to study drug; number of Serious Adverse Events (SAEs) related and not related to study drug

8 secondary outcomes

Change in Potassium Level From Baseline in Lisinopril-naive Participants
Time frame: At baseline visit and Day 14 prior to final study dose.
Worse Post-dose Decrease in Estimated Glomerular Filtration Rate (eGFR) From Baseline in Lisinopril-naive Participants
Time frame: Baseline to Day 14 (+/- 3 days)
Largest eGFR Percent Decrease From Baseline in Lisinopril-naive Participants
Time frame: Baseline to Day 14 (+/- 3 days)
Change in Urine Protein/Creatinine From Baseline in Lisinopril-naive Participants.
Time frame: Baseline to worst post-dose before Day 14 (+/- 3 days)
Change in Diastolic Blood Pressure From Baseline in Lisinopril-naive Participants
Time frame: Baseline to Day 14 (+/-3 days)
Change in Systolic Blood Pressure From Baseline in Lisinopril-naive Participants
Time frame: Baseline to Day 14 (+/- 3 days)
Change in Systolic Blood Pressure (BP) From Baseline in Lisinopril SOC Group
Time frame: Screening to Day 14 to 40
Change in Diastolic Blood Pressure From Baseline in Lisinopril SOC Group
Time frame: Screening to Day 14 to 40

Results and safety

Results posted to the registry on 8 Jul 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Low Dose: Lisinopril	13	12
Medium Dose: Lisinopril	10	8
High Dose: Lisinopril	3	2

Primary outcome: Pharmacokinetics (PK) - Area Under the Plasma Concentration-time Curve (AUC)

Time frame: Day 14 (+/- 3 days) of lisinopril therapy at hours 0 (pre-dose) and 1,2,4,5,8,12 and 24 hrs after dose. Geometric mean (Geometric Coefficient of Variation). Unit: ng*h/mL

Measure	Low Dose: Lisinopril n = 12	Medium Dose: Lisinopril n = 8	High Dose: Lisinopril n = 2
Value	298 (46.5)	640 (28.6)	702 (66.4)

Primary outcome: PK - Maximum Observed Concentration of Drug in Plasma (Cmax)

Time frame: Day14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after dose. Geometric mean (Geometric Coefficient of Variation). Unit: ng/ml

Measure	Low Dose: Lisinopril n = 12	Medium Dose: Lisinopril n = 8	High Dose: Lisinopril n = 2
Value	20.9 (41.2)	47.7 (25.1)	58.0 (41.2)

Primary outcome: PK - Time of the Maximum Observed Concentration in Plasma (Tmax)

Time frame: Day 14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after dose. Median (Full Range). Unit: hours

Measure	Low Dose: Lisinopril n = 12	Medium Dose: Lisinopril n = 8	High Dose: Lisinopril n = 2
Value	5.0 (4.0 to 8.1)	5.0 (4.0 to 8.0)	4.5 (4.0 to 5.0)

Primary outcome: PK - Oral Clearance (CL/F)

Time frame: Day 14 (+/- 3 d) of dose at 0 hour and at 1, 2, 4, 5, 8, 12, and 24 hrs after dose. Geometric mean (Geometric Coefficient of Variation). Unit: L/h/70 kg

Measure	Low Dose: Lisinopril n = 12	Medium Dose: Lisinopril n = 8	High Dose: Lisinopril n = 2
Value	17.9 (61.2)	18.6 (34.4)	32.8 (54.1)

8 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Low Dose: Lisinopril	0 of 12 (0%)	5 of 12 (41.7%)	Not reported
Medium Dose: Lisinopril	1 of 8 (12.5%)	4 of 8 (50%)	Not reported
High Dose: Lisinopril	0 of 2 (0%)	2 of 2 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 15286277National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004 Aug;114(2 Suppl 4th Report):555-76. No abstract available.
Background: PubMed 18713951Knutter I, Wollesky C, Kottra G, Hahn MG, Fischer W, Zebisch K, Neubert RH, Daniel H, Brandsch M. Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited. J Pharmacol Exp Ther. 2008 Nov;327(2):432-41. doi: 10.1124/jpet.108.143339. Epub 2008 Aug 19.
Background: PubMed 2900730Lin JH, Chen IW, Ulm EH, Duggan DE. Differential renal handling of angiotensin-converting enzyme inhibitors enalaprilat and lisinopril in rats. Drug Metab Dispos. 1988 May-Jun;16(3):392-6.
Background: PubMed 17216247Hogg RJ, Delucchi A, Sakihara G, Wells TG, Tenney F, Batisky DL, Blumer JL, Vogt BA, Lo MW, Hand E, Panebianco D, Rippley R, Shaw W, Shahinfar S. A multicenter study of the pharmacokinetics of lisinopril in pediatric patients with hypertension. Pediatr Nephrol. 2007 May;22(5):695-701. doi: 10.1007/s00467-006-0399-5. Epub 2007 Jan 10.
BackgroundPrinivil® (lisinopril tablets) package insert; Whitehouse Station, NJ: Merck & Co., Inc.; 2003
Background: PubMed 12915832Mitsnefes MM, Khoury PR, McEnery PT. Early posttransplantation hypertension and poor long-term renal allograft survival in pediatric patients. J Pediatr. 2003 Jul;143(1):98-103. doi: 10.1016/S0022-3476(03)00209-9.
Background: PubMed 17976120Silverstein DM, Leblanc P, Hempe JM, Ramcharan T, Boudreaux JP. Tracking of blood pressure and its impact on graft function in pediatric renal transplant patients. Pediatr Transplant. 2007 Dec;11(8):860-7. doi: 10.1111/j.1399-3046.2007.00753.x.
Background: PubMed 11422817Mitsnefes MM, Omoloja A, McEnery PT. Short-term pediatric renal transplant survival: blood pressure and allograft function. Pediatr Transplant. 2001 Jun;5(3):160-5. doi: 10.1034/j.1399-3046.2001.t01-1-00051.x.
Background: PubMed 19584673Cross NB, Webster AC, Masson P, O'connell PJ, Craig JC. Antihypertensives for kidney transplant recipients: systematic review and meta-analysis of randomized controlled trials. Transplantation. 2009 Jul 15;88(1):7-18. doi: 10.1097/TP.0b013e3181a9e960.
Background: PubMed 10731054Sorof JM, Goldstein SL, Brewer ED, Steiger HM, Portman RJ. Use of anti-hypertensive medications and post-transplant renal allograft function in children. Pediatr Transplant. 2000 Feb;4(1):21-7. doi: 10.1034/j.1399-3046.2000.00082.x.
Background: PubMed 20508862Hernandez AA, Moreso F, Bayes B, Lauzurica R, Sanz-Guajardo D, Gomez-Huertas E, Pereira P, Paul J, Crespo J, Amenabar JJ, Oliver J, Seron D. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in renal transplantation between 1990 and 2002 in Spain. NDT Plus. 2010 Jun;3(Suppl_2):ii21-ii25. doi: 10.1093/ndtplus/sfq068.
Background: PubMed 18234845Mitterbauer C, Heinze G, Kainz A, Kramar R, Horl WH, Oberbauer R. ACE-inhibitor or AT2-antagonist therapy of renal transplant recipients is associated with an increase in serum potassium concentrations. Nephrol Dial Transplant. 2008 May;23(5):1742-6. doi: 10.1093/ndt/gfm864. Epub 2008 Jan 30.
Pediatric Trials Network (PTN)Link provided by the sponsor.
The Eunice Kennedy Shriver National Institute of Child Health and HumanLink provided by the sponsor.
Information about LisinoprilLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Daniel Benjamin, MD, PhD, MPH study director

Duke University

Howard Trachtman, MD study chair

NYU Langone Health

Uptal D Patel, MD principal investigator

Duke University

7 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Lisinopril in people with Hypertension, run by Uptal Patel at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Jul 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetics (PK) - Area Under the Plasma Concentration-time Curve (AUC) (time frame: Day 14 (+/- 3 days) of lisinopril therapy at hours 0 (pre-dose) and 1,2,4,5,8,12 and 24 hrs after dose). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01491919, which also lists 34 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2015.