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| ID | Type | Description | Link |
|---|---|---|---|
| HHSN275201000003I | Other Identifier | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) |
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| Name | Class |
|---|---|
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
| The Emmes Company, LLC | INDUSTRY |
| University of Rochester | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Low Dose: Lisinopril | Experimental | Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day |
|
| Medium Dose: Lisinopril | Experimental | Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lisinopril | Drug | Subjects will be randomized to Low, Medium, or High dose of Lisinopril |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. | 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. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Daniel Benjamin, MD, PhD, MPH | Duke University | Study Director |
| Howard Trachtman, MD | NYU Langone Health | Study Chair |
| Uptal D Patel, MD | Duke University | Principal Investigator |
| Adam Frymoyer, MD | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama | Birmingham | Alabama | 35233 | United States | ||
| Arkansas Children's Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15286277 | Background | 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. | |
| 18713951 | Background |
| Label | URL |
|---|---|
| Pediatric Trials Network (PTN) | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Low Dose: Lisinopril | Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day |
| FG001 | Medium Dose: Lisinopril | Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day |
| FG002 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Low Dose: Lisinopril | Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day |
| BG001 | Medium Dose: Lisinopril | Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Day 14 (+/- 3 days) of lisinopril therapy at hours 0 (pre-dose) and 1,2,4,5,8,12 and 24 hrs after dose |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Low Dose: Lisinopril | Participants will receive study medication for 14±3 days at a dose 0.1 mg/kg/day |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastroenteritis | Infections and infestations |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Uptal Patel, MD | Duke Clinical Research Institute | 919-668-4601 | uptal.patel@duke.edu |
Not provided
| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D017706 | Lisinopril |
| ID | Term |
|---|---|
| D004151 | Dipeptides |
| D009842 | Oligopeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
Not provided
Not provided
| OpAns, LLC |
| UNKNOWN |
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| 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 | First dose of study drug to 30 days after final study visit for AEs and until resolution for SAEs |
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. |
| 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. | 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. | 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. | 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. | 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. | 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. | Screening to Day 14 to 40 |
| Little Rock |
| Arkansas |
| 72202 |
| United States |
| Emory University and Children's Healthcare of Atlanta | Atlanta | Georgia | 30322 | United States |
| University of Michigan | Ann Arbor | Michigan | 48109 | United States |
| Children's Mercy Hospitals & Clinics | Kansas City | Missouri | 64108 | United States |
| New York University Langone Medical Center | New York | New York | 10016 | United States |
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229 | United States |
| 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. |
| 2900730 | Background | 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. |
| 17216247 | Background | 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. |
| Background | Prinivil® (lisinopril tablets) package insert; Whitehouse Station, NJ: Merck & Co., Inc.; 2003 |
| 12915832 | Background | 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. |
| 17976120 | Background | 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. |
| 11422817 | Background | 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. |
| 19584673 | Background | 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. |
| 10731054 | Background | 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. |
| 20508862 | Background | 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. |
| 18234845 | Background | 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. |
| 17845569 | Background | 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. |
| 19930314 | Background | 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. |
| 11274244 | Background | 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. |
| 20854382 | Background | Nielsen SE, Schjoedt KJ, Astrup AS, Tarnow L, Lajer M, Hansen PR, Parving HH, Rossing P. Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Kidney Injury Molecule 1 (KIM1) in patients with diabetic nephropathy: a cross-sectional study and the effects of lisinopril. Diabet Med. 2010 Oct;27(10):1144-50. doi: 10.1111/j.1464-5491.2010.03083.x. |
| 17425758 | Background | Halimi JM, Giraudeau B, Buchler M, Al-Najjar A, Etienne I, Laouad I, Bruyere F, Lebranchu Y. Enalapril/amlodipine combination in cyclosporine-treated renal transplant recipients: a prospective randomized trial. Clin Transplant. 2007 Mar-Apr;21(2):277-84. doi: 10.1111/j.1399-0012.2007.00643.x. |
| 19154107 | Background | Spooner N, Lad R, Barfield M. Dried blood spots as a sample collection technique for the determination of pharmacokinetics in clinical studies: considerations for the validation of a quantitative bioanalytical method. Anal Chem. 2009 Feb 15;81(4):1557-63. doi: 10.1021/ac8022839. |
| 19158356 | Background | Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009 Mar;20(3):629-37. doi: 10.1681/ASN.2008030287. Epub 2009 Jan 21. |
| 14553956 | Background | Soffer B, Zhang Z, Miller K, Vogt BA, Shahinfar S. A double-blind, placebo-controlled, dose-response study of the effectiveness and safety of lisinopril for children with hypertension. Am J Hypertens. 2003 Oct;16(10):795-800. doi: 10.1016/s0895-7061(03)00900-2. |
| 12533979 | Background | Thompson KC, Zhao Z, Mazakas JM, Beasley CA, Reed RA, Moser CL. Characterization of an extemporaneous liquid formulation of lisinopril. Am J Health Syst Pharm. 2003 Jan 1;60(1):69-74. doi: 10.1093/ajhp/60.1.69. |
| Background | 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. |
| 18846389 | Background | Rhodin MM, Anderson BJ, Peters AM, Coulthard MG, Wilkins B, Cole M, Chatelut E, Grubb A, Veal GJ, Keir MJ, Holford NH. Human renal function maturation: a quantitative description using weight and postmenstrual age. Pediatr Nephrol. 2009 Jan;24(1):67-76. doi: 10.1007/s00467-008-0997-5. Epub 2008 Oct 10. |
| 2539850 | Background | Thomson AH, Kelly JG, Whiting B. Lisinopril population pharmacokinetics in elderly and renal disease patients with hypertension. Br J Clin Pharmacol. 1989 Jan;27(1):57-65. doi: 10.1111/j.1365-2125.1989.tb05335.x. |
| 12043359 | Background | Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, Mei Z, Wei R, Curtin LR, Roche AF, Johnson CL. 2000 CDC Growth Charts for the United States: methods and development. Vital Health Stat 11. 2002 May;(246):1-190. |
| 19892427 | Background | Bazzoli C, Retout S, Mentre F. Design evaluation and optimisation in multiple response nonlinear mixed effect models: PFIM 3.0. Comput Methods Programs Biomed. 2010 Apr;98(1):55-65. doi: 10.1016/j.cmpb.2009.09.012. Epub 2009 Nov 4. |
| 16690893 | Background | Sayed-Tabatabaei FA, Oostra BA, Isaacs A, van Duijn CM, Witteman JC. ACE polymorphisms. Circ Res. 2006 May 12;98(9):1123-33. doi: 10.1161/01.RES.0000223145.74217.e7. |
| 12359978 | Background | Wuhl E, Witte K, Soergel M, Mehls O, Schaefer F; German Working Group on Pediatric Hypertension. Distribution of 24-h ambulatory blood pressure in children: normalized reference values and role of body dimensions. J Hypertens. 2002 Oct;20(10):1995-2007. doi: 10.1097/00004872-200210000-00019. |
| 9042117 | Background | Soergel M, Kirschstein M, Busch C, Danne T, Gellermann J, Holl R, Krull F, Reichert H, Reusz GS, Rascher W. Oscillometric twenty-four-hour ambulatory blood pressure values in healthy children and adolescents: a multicenter trial including 1141 subjects. J Pediatr. 1997 Feb;130(2):178-84. doi: 10.1016/s0022-3476(97)70340-8. |
| 19846849 | Background | ESCAPE Trial Group; Wuhl E, Trivelli A, Picca S, Litwin M, Peco-Antic A, Zurowska A, Testa S, Jankauskiene A, Emre S, Caldas-Afonso A, Anarat A, Niaudet P, Mir S, Bakkaloglu A, Enke B, Montini G, Wingen AM, Sallay P, Jeck N, Berg U, Caliskan S, Wygoda S, Hohbach-Hohenfellner K, Dusek J, Urasinski T, Arbeiter K, Neuhaus T, Gellermann J, Drozdz D, Fischbach M, Moller K, Wigger M, Peruzzi L, Mehls O, Schaefer F. Strict blood-pressure control and progression of renal failure in children. N Engl J Med. 2009 Oct 22;361(17):1639-50. doi: 10.1056/NEJMoa0902066. |
| 17848393 | Background | Knoll GA, Cantarovitch M, Cole E, Gill J, Gourishankar S, Holland D, Kiberd B, Muirhead N, Prasad R, Tibbles LA, Treleaven D, Fergusson D. The Canadian ACE-inhibitor trial to improve renal outcomes and patient survival in kidney transplantation--study design. Nephrol Dial Transplant. 2008 Jan;23(1):354-8. doi: 10.1093/ndt/gfm574. Epub 2007 Sep 10. |
| 16760444 | Background | Cooper WO, Hernandez-Diaz S, Arbogast PG, Dudley JA, Dyer S, Gideon PS, Hall K, Ray WA. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med. 2006 Jun 8;354(23):2443-51. doi: 10.1056/NEJMoa055202. |
| 18678786 | Background | Urbina E, Alpert B, Flynn J, Hayman L, Harshfield GA, Jacobson M, Mahoney L, McCrindle B, Mietus-Snyder M, Steinberger J, Daniels S; American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee. Ambulatory blood pressure monitoring in children and adolescents: recommendations for standard assessment: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee of the council on cardiovascular disease in the young and the council for high blood pressure research. Hypertension. 2008 Sep;52(3):433-51. doi: 10.1161/HYPERTENSIONAHA.108.190329. Epub 2008 Aug 4. No abstract available. |
| 25807932 | Derived | Trachtman H, Frymoyer A, Lewandowski A, Greenbaum LA, Feig DI, Gipson DS, Warady BA, Goebel JW, Schwartz GJ, Lewis K, Anand R, Patel UD; Best Pharmaceuticals for Children Act-Pediatric Trials Network Administrative Core Committee. Pharmacokinetics, Pharmacodynamics, and Safety of Lisinopril in Pediatric Kidney Transplant Patients: Implications for Starting Dose Selection. Clin Pharmacol Ther. 2015 Jul;98(1):25-33. doi: 10.1002/cpt.127. Epub 2015 May 2. |
| The Eunice Kennedy Shriver National Institute of Child Health and Human | View source |
| Information about Lisinopril | View source |
| BG002 | 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. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Estimated glomerular filtration rate (eGFR) | 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. | Mean | Standard Deviation | ml/min per 1.73m^2 |
|
| Time since transplant | Mean | Standard Deviation | years |
|
| Ethnicity | Number | participants |
|
| Weight | Mean | Standard Deviation | kg |
|
| OG002 | 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. |
|
|
| Primary | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/ml | Day14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after dose |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | mEq/L | At baseline visit and Day 14 prior to final study dose. |
|
|
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| Secondary | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Baseline to Day 14 (+/- 3 days) |
|
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| Primary | 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. | Posted | Median | Full Range | hours | Day 14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after dose |
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| Primary | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/h/70 kg | Day 14 (+/- 3 d) of dose at 0 hour and at 1, 2, 4, 5, 8, 12, and 24 hrs after dose |
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| Primary | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/h/70 kg | Day 14 (+/- 3 d) of dose at 0 hour and 1, 2, 4, 5, 8, 12, and 24 hrs after dose. |
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| Primary | 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 | Posted | Number | events | First dose of study drug to 30 days after final study visit for AEs and until resolution for SAEs |
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| Secondary | 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. | Posted | Number | percentage | Baseline to Day 14 (+/- 3 days) |
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| Secondary | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | mg/mg | Baseline to worst post-dose before Day 14 (+/- 3 days) |
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| Secondary | 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. | Change in diastolic blood pressure from baseline is reported here for lisinopril-naive participants (not the standard of care group which are reported separately). | Posted | Mean | Standard Deviation | mmHg | Baseline to Day 14 (+/-3 days) |
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| Secondary | 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. | 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). | Posted | Mean | Standard Deviation | mmHg | Baseline to Day 14 (+/- 3 days) |
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| Secondary | 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. | Change in systolic blood pressure from baseline is reported here for lisinopril SOCparticipants (not the Lisinopril-naive group which are reported separately). | Posted | Mean | Standard Deviation | mmHg | Screening to Day 14 to 40 |
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| Secondary | 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. | Change in diastolic blood pressure from baseline is reported here for lisinopril SOCparticipants (not the Lisinopril-naive group which are reported separately). | Posted | Mean | Standard Deviation | mmHg | Screening to Day 14 to 40 |
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| 0 |
| 12 |
| 5 |
| 12 |
| EG001 | Medium Dose: Lisinopril | Participants will receive study medication for 14±3 days at a dose 0.2 mg/kg/day | 1 | 8 | 4 | 8 |
| EG002 | 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. | 0 | 2 | 2 | 2 |
| Abdominal pain upper | Gastrointestinal disorders |
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| Diarrhea | Gastrointestinal disorders |
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| Nausea | Gastrointestinal disorders |
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| Retching | Gastrointestinal disorders |
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| Vomiting | Gastrointestinal disorders |
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| Infusion site extravasation | General disorders |
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| Infusion site pain | General disorders |
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| Infusion site pruritus | General disorders |
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| Otitis externa | Infections and infestations |
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| Upper limb fracture | Injury, poisoning and procedural complications |
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| Glomerular filtration rate decreased | Investigations |
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| Hemoglobin decreased | Investigations |
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| Dizziness | Nervous system disorders |
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| Headache | Nervous system disorders |
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| Rash | Skin and subcutaneous tissue disorders |
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Not provided
Not provided
| AEs not related to study drug |
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| SAE |
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| SAE not related to study drug |
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| eGFR >=60 ml/min per 1.73m^2 (n=3, 5, 3) |
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| eGFR >+60 ml/min per 1.732 (n=3, 5, 3) |
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