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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01491919
Recruitment Status : Completed
First Posted : December 14, 2011
Results First Posted : July 8, 2015
Last Update Posted : July 8, 2015
Sponsor:
Collaborators:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
The EMMES Corporation
University of Rochester
OpAns, LLC
Information provided by (Responsible Party):
Uptal Patel, Duke University

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hypertension
Intervention Drug: Lisinopril
Enrollment 26
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Low Dose: Lisinopril Medium Dose: Lisinopril High Dose: Lisinopril
Hide Arm/Group Description Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day 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.
Period Title: Overall Study
Started 13 10 3
Completed 12 8 2
Not Completed 1 2 1
Reason Not Completed
Insufficient PK sampling             1             2             1
Arm/Group Title Low Dose: Lisinopril Medium Dose: Lisinopril High Dose: Lisinopril Total
Hide Arm/Group Description Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day 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. Total of all reporting groups
Overall Number of Baseline Participants 12 8 2 22
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 8 participants 2 participants 22 participants
14.9  (2.3) 13.0  (3) 9.5  (3.5) 13.8  (3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 8 participants 2 participants 22 participants
Female
4
  33.3%
2
  25.0%
1
  50.0%
7
  31.8%
Male
8
  66.7%
6
  75.0%
1
  50.0%
15
  68.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 8 participants 2 participants 22 participants
American Indian or Alaska Native
0
   0.0%
1
  12.5%
0
   0.0%
1
   4.5%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
  25.0%
4
  50.0%
0
   0.0%
7
  31.8%
White
7
  58.3%
2
  25.0%
2
 100.0%
11
  50.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
2
  16.7%
1
  12.5%
0
   0.0%
3
  13.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 12 participants 8 participants 2 participants 22 participants
12 8 2 22
Estimated glomerular filtration rate (eGFR)   [1] 
Mean (Standard Deviation)
Unit of measure:  Ml/min per 1.73m^2
Number Analyzed 12 participants 8 participants 2 participants 22 participants
72.5  (25.7) 62  (16.7) 89.3  (44.4) 70.2  (24.4)
[1]
Measure Description:

Estimated glomerular filtration rate (eGFR) calculated by modified Schwartz formula [=0.413 x Length (cm)/serum creatinine (mg/dl)].

Note: text verified with protocol on 4/2/15 as '413xLength'. Added spaces for clarification.

Time since transplant  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 8 participants 2 participants 22 participants
4.8  (4.7) 4.9  (3.4) 0.9  (0.4) 4.5  (4.1)
Ethnicity  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 12 participants 8 participants 2 participants 22 participants
Hispanic/Latino 2 2 0 4
Non-hispanic/non-latino 10 6 2 18
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 12 participants 8 participants 2 participants 22 participants
56.8  (19.4) 50.2  (28.7) 23.1  (3.0) 51.3  (23.8)
1.Primary Outcome
Title Pharmacokinetics (PK) - Area Under the Plasma Concentration-time Curve (AUC)
Hide Description 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.
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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Low Dose: Lisinopril Medium Dose: Lisinopril High Dose: Lisinopril
Hide Arm/Group Description:
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
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.
Overall Number of Participants Analyzed 12 8 2
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
298
(46.5%)
640
(28.6%)
702
(66.4%)
2.Primary Outcome
Title PK - Maximum Observed Concentration of Drug in Plasma (Cmax)
Hide Description 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.
Time Frame Day14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Low Dose: Lisinopril Medium Dose: Lisinopril High Dose: Lisinopril
Hide Arm/Group Description:
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
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.
Overall Number of Participants Analyzed 12 8 2
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/ml
20.9
(41.2%)
47.7
(25.1%)
58.0
(41.2%)
3.Primary Outcome
Title PK - Time of the Maximum Observed Concentration in Plasma (Tmax)
Hide Description 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.
Time Frame Day 14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Low Dose: Lisinopril Medium Dose: Lisinopril High Dose: Lisinopril
Hide Arm/Group Description:
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
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.
Overall Number of Participants Analyzed 12 8 2
Median (Full Range)
Unit of Measure: hours
5.0
(4.0 to 8.1)
5.0
(4.0 to 8.0)
4.5
(4.0 to 5.0)
4.Primary Outcome
Title PK - Oral Clearance (CL/F)
Hide Description 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.
Time Frame Day 14 (+/- 3 d) of dose at 0 hour and at 1, 2, 4, 5, 8, 12, and 24 hrs after dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Low Dose: Lisinopril Medium Dose: Lisinopril High Dose: Lisinopril
Hide Arm/Group Description:
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
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.
Overall Number of Participants Analyzed 12 8 2
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L/h/70 kg
17.9
(61.2%)
18.6
(34.4%)
32.8
(54.1%)
5.Primary Outcome
Title PK Renal Clearance (CLrenal)
Hide Description 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.
Time Frame Day 14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after dose.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Low Dose: Lisinopril Medium Dose: Lisinopril High Dose: Lisinopril
Hide Arm/Group Description:
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
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.
Overall Number of Participants Analyzed 12 8 2
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L/h/70 kg
3.4
(60.4%)
3.4
(46.0%)
6.8
(94.4%)
6.Primary Outcome
Title Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) During/After Study Drug Administration
Hide Description 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
Time Frame First dose of study drug to 30 days after final study visit for AEs and until resolution for SAEs
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Lisinopril-naive Lisinopril Standard of Care (SOC)
Hide Arm/Group Description:
These protocol participants were not randomized. Instead, the older age group (7-17 years) were first enrolled consecutively into each dose level, starting with the lowest dose level (0.1 mg/kg per day). After enrollment is complete in the low dose level for an eGFR strata, enrollment will commence for the intermediate (0.2 mg/kg per day) dosage in that strata, followed by the high (0.4 mg/kg per day) dosage level. Enrollment for the 2-6 years age group did not begin until enrollment in the older age group (7-17 years) for the low and intermediate dosage level at each eGFR strata is complete.
These protocol participants were enrolled and continued on the lisinopril dose prescribed as standard of care. They were assigned to the appropriate eGFR and dose level stratum (rounding to the closest dose level). Since the lisinopril dose was assigned based on standard of care, a patient was enrolled without regard to open/closed status of the dose stratum in this group. Therefore, over enrollment of a specific dose and eGFR stratum was allowed for participants enrolled he the Lisinopril-naive group to accommodate these valuable low-risk participants already taking lisinopril.
Overall Number of Participants Analyzed 15 11
Measure Type: Number
Unit of Measure: events
AEs 12 12
AE related to study drug 5 0
AEs not related to study drug 7 12
SAE 1 0
SAE not related to study drug 1 0
7.Secondary Outcome
Title Change in Potassium Level From Baseline in Lisinopril-naive Participants
Hide Description Potassium values will be obtained at Baseline and Day 14 prior to the final dose of study drug. Mean calculated from the two measurements.
Time Frame At baseline visit and Day 14 prior to final study dose.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Low Dose: Lisinopril Medium Dose: Lisinopril High Dose: Lisinopril
Hide Arm/Group Description:
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
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.
Overall Number of Participants Analyzed 6 6 3
Mean (Standard Deviation)
Unit of Measure: mEq/L
0.1  (0.3) -0.3  (0.6) 0.3  (0.5)
8.Secondary Outcome
Title Worse Post-dose Decrease in Estimated Glomerular Filtration Rate (eGFR) From Baseline in Lisinopril-naive Participants
Hide Description 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.
Time Frame Baseline to Day 14 (+/- 3 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Low Dose: Lisinopril Medium Dose: Lisinopril High Dose: Lisinopril
Hide Arm/Group Description:
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
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.
Overall Number of Participants Analyzed 6 6 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
1
(14%)
1.02
(10%)
0.89
(14%)
9.Secondary Outcome
Title Largest eGFR Percent Decrease From Baseline in Lisinopril-naive Participants
Hide Description

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.

Time Frame Baseline to Day 14 (+/- 3 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Low Dose: Lisinopril Medium Dose: Lisinopril High Dose: Lisinopril
Hide Arm/Group Description:
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
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.
Overall Number of Participants Analyzed 6 6 3
Measure Type: Number
Unit of Measure: percentage
15 12 21
10.Secondary Outcome
Title Change in Urine Protein/Creatinine From Baseline in Lisinopril-naive Participants.
Hide Description 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.
Time Frame Baseline to worst post-dose before Day 14 (+/- 3 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Low Dose: Lisinopril Medium Dose: Lisinopril High Dose: Lisinopril
Hide Arm/Group Description:
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
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.
Overall Number of Participants Analyzed 6 6 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mg/mg
-0.45
(0.6%)
-0.08
(0.15%)
-0.74
(1.37%)
11.Secondary Outcome
Title Change in Diastolic Blood Pressure From Baseline in Lisinopril-naive Participants
Hide Description

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.

Time Frame Baseline to Day 14 (+/-3 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Change in diastolic blood pressure from baseline is reported here for lisinopril-naive participants (not the standard of care group which are reported separately).
Arm/Group Title Low Dose: Lisinopril Medium Dose: Lisinopril High Dose: Lisinopril
Hide Arm/Group Description:
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
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.
Overall Number of Participants Analyzed 6 6 3
Mean (Standard Deviation)
Unit of Measure: mmHg
eGFR 30-59 ml/min per 1.73m^2 (n=3, 1, 0) -4.0  (20) 7.0  (0) NA [1]   (NA)
eGFR >=60 ml/min per 1.73m^2 (n=3, 5, 3) -9.0  (7.5) -6.0  (6.7) -4.0  (5.3)
[1]
no participants in this category
12.Secondary Outcome
Title Change in Systolic Blood Pressure From Baseline in Lisinopril-naive Participants
Hide Description

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.

Time Frame Baseline to Day 14 (+/- 3 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Change in systolic blood pressure from baseline is reported here for lisinopril-naive participants (not the standard of care (SOC) group which are reported separately).
Arm/Group Title Low Dose: Lisinopril Medium Dose: Lisinopril High Dose: Lisinopril
Hide Arm/Group Description:
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
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.
Overall Number of Participants Analyzed 6 6 3
Mean (Standard Deviation)
Unit of Measure: mmHg
eGFR 30-59 ml/min per 1.73m2 (n=3, 1, 0) -5.0  (11.4) -6.0  (0) NA [1]   (NA)
eGFR >+60 ml/min per 1.732 (n=3, 5, 3) -6.7  (4.0) -8.8  (11.7) -11.3  (2.1)
[1]
no participants in this category
13.Secondary Outcome
Title Change in Systolic Blood Pressure (BP) From Baseline in Lisinopril SOC Group
Hide Description 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.
Time Frame Screening to Day 14 to 40
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Change in systolic blood pressure from baseline is reported here for lisinopril SOCparticipants (not the Lisinopril-naive group which are reported separately).
Arm/Group Title Low Dose: Lisinopril Medium Dose: Lisinopril High Dose: Lisinopril
Hide Arm/Group Description:
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
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.
Overall Number of Participants Analyzed 7 4 0
Mean (Standard Deviation)
Unit of Measure: mmHg
eGFR 30-59 ml/min per 1.73m2 (n=2, 2, 0) -6.0  (17) -1.0  (4.2)
eGFR >=60 ml/min per 1.73m2 (n=5, 2, 0) 6.4  (6.9) -1.0  (0)
14.Secondary Outcome
Title Change in Diastolic Blood Pressure From Baseline in Lisinopril SOC Group
Hide Description 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.
Time Frame Screening to Day 14 to 40
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Change in diastolic blood pressure from baseline is reported here for lisinopril SOCparticipants (not the Lisinopril-naive group which are reported separately).
Arm/Group Title Low Dose: Lisinopril Medium Dose: Lisinopril High Dose: Lisinopril
Hide Arm/Group Description:
Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day
Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day
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.
Overall Number of Participants Analyzed 7 4 0
Mean (Standard Deviation)
Unit of Measure: mmHg
eGFR 30-59 ml/min per 1.73m2 (n=2, 2, 0) -6.0  (5.7) -6.5  (9.2)
eGFR >=60 ml/min per 1.73m2 (n=5, 2, 0) 3.4  (14.0) -3.0  (0)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Low Dose: Lisinopril Medium Dose: Lisinopril High Dose: Lisinopril
Hide Arm/Group Description Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day 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.
All-Cause Mortality
Low Dose: Lisinopril Medium Dose: Lisinopril High Dose: Lisinopril
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Low Dose: Lisinopril Medium Dose: Lisinopril High Dose: Lisinopril
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/12 (0.00%)   1/8 (12.50%)   0/2 (0.00%) 
Infections and infestations       
Gastroenteritis  0/12 (0.00%)  1/8 (12.50%)  0/2 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Low Dose: Lisinopril Medium Dose: Lisinopril High Dose: Lisinopril
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/12 (41.67%)   4/8 (50.00%)   2/2 (100.00%) 
Blood and lymphatic system disorders       
Anaemia  1/12 (8.33%)  0/8 (0.00%)  0/2 (0.00%) 
Gastrointestinal disorders       
Abdominal pain upper  1/12 (8.33%)  2/8 (25.00%)  0/2 (0.00%) 
Diarrhea  0/12 (0.00%)  2/8 (25.00%)  0/2 (0.00%) 
Nausea  1/12 (8.33%)  1/8 (12.50%)  0/2 (0.00%) 
Retching  0/12 (0.00%)  2/8 (25.00%)  0/2 (0.00%) 
Vomiting  0/12 (0.00%)  0/8 (0.00%)  1/2 (50.00%) 
General disorders       
Infusion site extravasation  1/12 (8.33%)  0/8 (0.00%)  0/2 (0.00%) 
Infusion site pain  1/12 (8.33%)  0/8 (0.00%)  0/2 (0.00%) 
Infusion site pruritus  1/12 (8.33%)  0/8 (0.00%)  0/2 (0.00%) 
Infections and infestations       
Otitis externa  0/12 (0.00%)  1/8 (12.50%)  0/2 (0.00%) 
Injury, poisoning and procedural complications       
Upper limb fracture  0/12 (0.00%)  0/8 (0.00%)  1/2 (50.00%) 
Investigations       
Glomerular filtration rate decreased  0/12 (0.00%)  0/8 (0.00%)  1/2 (50.00%) 
Hemoglobin decreased  0/12 (0.00%)  0/8 (0.00%)  1/2 (50.00%) 
Nervous system disorders       
Dizziness  0/12 (0.00%)  2/8 (25.00%)  0/2 (0.00%) 
Headache  1/12 (8.33%)  1/8 (12.50%)  0/2 (0.00%) 
Skin and subcutaneous tissue disorders       
Rash  1/12 (8.33%)  0/8 (0.00%)  0/2 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Uptal Patel, MD
Organization: Duke Clinical Research Institute
Phone: 919-668-4601
Publications:
Prinivil® (lisinopril tablets) package insert; Whitehouse Station, NJ: Merck & Co., Inc.; 2003
CDER Approval Package for Prinivil®: Application Number 19-558/S-043. Clinical Pharmacology and Biopharmaceutics Review. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/19-558S043_Prinivil.cfm. Last accessed Jan. 6, 2011.
Responsible Party: Uptal Patel, Duke University
ClinicalTrials.gov Identifier: NCT01491919     History of Changes
Other Study ID Numbers: Pro00029537
HHSN275201000003I ( Other Identifier: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
First Submitted: November 29, 2011
First Posted: December 14, 2011
Results First Submitted: April 27, 2015
Results First Posted: July 8, 2015
Last Update Posted: July 8, 2015