|February 18, 2020
|February 20, 2020
|October 14, 2020
|March 5, 2020
|April 24, 2024 (Final data collection date for primary outcome measure)
- Clearance (CL) or apparent oral clearance (CL/F) as measured by PK sampling [ Time Frame: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days. ]
- Volume of distribution (V) or apparent oral volume of distribution (V/F) as measured by PK sampling [ Time Frame: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days. ]
- Elimination rate constant (ke) as measured by PK sampling [ Time Frame: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days. ]
- Half-life (t1/2) as measured by PK sampling [ Time Frame: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days. ]
- Absorption rate constant (ka) as measured by PK sampling [ Time Frame: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days. ]
- AUC (area under the curve) as measured by PK sampling [ Time Frame: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days. ]
- Maximum concentration (Cmax) as measured by PK sampling [ Time Frame: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days. ]
- Time to achieve maximum concentration (Tmax) as measured by PK sampling [ Time Frame: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days. ]
|Same as current
|Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children Per Standard of Care (POPS)
|Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs
|The study investigators are interested in learning more about how drugs, that are given to children by their health care provider, act in the bodies of children and young adults in hopes to find the most safe and effective dose for children. The primary objective of this study is to evaluate the PK of understudied drugs currently being administered to children per SOC as prescribed by their treating provider.
|Observational Model: Other
Time Perspective: Prospective
|Retention: Samples With DNA
Whole blood, effluent samples, and plasma.
|Children under 21 years of age.
- Coronavirus Infection (COVID-19)
- Pulmonary Arterial Hypertension
- Urinary Tract Infections in Children
- Primary Hyperaldosteronism
- Heart Failure
- Skin Infection
- Asthma in Children
- Bronchopulmonary Dysplasia
- Adrenal Insufficiency
- Fibrinolysis; Hemorrhage
- Attention Deficit Hyperactivity Disorder
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Kawasaki Disease
- Coagulation Disorder
- Down Syndrome
|Drug: The POP02 study is collecting bodily fluid samples (i.e., whole blood, effluent samples) of children prescribed the following drugs of interest per standard of care:
The prescribing of drugs to children is not part of this protocol. Participants will receive DOIs as prescribed by their treating provider.
- Aminocaproic acid
- Sevelamer Carbonate / Sevelamer Hydrochloride
- Tranexamic acid
|Children and young adults who are prescribed drugs of interest
Children and young adults who are prescribed drugs of interest as part of their routine medical care OR are SARS-CoV-2 positive.
Intervention: Drug: The POP02 study is collecting bodily fluid samples (i.e., whole blood, effluent samples) of children prescribed the following drugs of interest per standard of care:
- Benjamin DK Jr, Smith PB, Murphy MD, Roberts R, Mathis L, Avant D, Califf RM, Li JS. Peer-reviewed publication of clinical trials completed for pediatric exclusivity. JAMA. 2006 Sep 13;296(10):1266-73.
- Phan H, Leder M, Fishley M, Moeller M, Nahata M. Off-label and unlicensed medication use and associated adverse drug events in a pediatric emergency department. Pediatr Emerg Care. 2010 Jun;26(6):424-30. doi: 10.1097/PEC.0b013e3181e057e1.
- Long D, Koren G, James A. Ethics of drug studies in infants: how many samples are required for accurate estimation of pharmacokinetic parameters in neonates? J Pediatr. 1987 Dec;111(6 Pt 1):918-21.
- European Union. Ethical considerations for clinical trials on medicinal products conducted with the paediatric population. Eur J Health Law. 2008 Jul;15(2):223-50.
- Wade KC, Wu D, Kaufman DA, Ward RM, Benjamin DK Jr, Sullivan JE, Ramey N, Jayaraman B, Hoppu K, Adamson PC, Gastonguay MR, Barrett JS; National Institute of Child Health and Development Pediatric Pharmacology Research Unit Network. Population pharmacokinetics of fluconazole in young infants. Antimicrob Agents Chemother. 2008 Nov;52(11):4043-9. doi: 10.1128/AAC.00569-08. Epub 2008 Sep 22.
- de Hoog M, Schoemaker RC, Mouton JW, van den Anker JN. Vancomycin population pharmacokinetics in neonates. Clin Pharmacol Ther. 2000 Apr;67(4):360-7.
- García B, Barcia E, Pérez F, Molina IT. Population pharmacokinetics of gentamicin in premature newborns. J Antimicrob Chemother. 2006 Aug;58(2):372-9. Epub 2006 Jun 16.
- Capparelli E, Hochwald C, Rasmussen M, Parham A, Bradley J, Moya F. Population pharmacokinetics of cefepime in the neonate. Antimicrob Agents Chemother. 2005 Jul;49(7):2760-6.
- Pullen J, Stolk LM, Nieman FH, Degraeuwe PL, van Tiel FH, Zimmermann LJ. Population pharmacokinetics and dosing of amoxicillin in (pre)term neonates. Ther Drug Monit. 2006 Apr;28(2):226-31.
- Tremoulet A, Le J, Poindexter B, Sullivan JE, Laughon M, Delmore P, Salgado A, Ian-U Chong S, Melloni C, Gao J, Benjamin DK Jr, Capparelli EV, Cohen-Wolkowiez M; Administrative Core Committee of the Best Pharmaceuticals for Children Act-Pediatric Trials Network. Characterization of the population pharmacokinetics of ampicillin in neonates using an opportunistic study design. Antimicrob Agents Chemother. 2014 Jun;58(6):3013-20. doi: 10.1128/AAC.02374-13. Epub 2014 Mar 10.
- Hornik CP, Benjamin DK Jr, Smith PB, Pencina MJ, Tremoulet AH, Capparelli EV, Ericson JE, Clark RH, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act-Pediatric Trials Network. Electronic Health Records and Pharmacokinetic Modeling to Assess the Relationship between Ampicillin Exposure and Seizure Risk in Neonates. J Pediatr. 2016 Nov;178:125-129.e1. doi: 10.1016/j.jpeds.2016.07.011. Epub 2016 Aug 10.
- Le J, Poindexter B, Sullivan JE, Laughon M, Delmore P, Blackford M, Yogev R, James LP, Melloni C, Harper B, Mitchell J, Benjamin DK Jr, Boakye-Agyeman F, Cohen-Wolkowiez M. Comparative Analysis of Ampicillin Plasma and Dried Blood Spot Pharmacokinetics in Neonates. Ther Drug Monit. 2018 Feb;40(1):103-108. doi: 10.1097/FTD.0000000000000466.
- Gonzalez D, Melloni C, Yogev R, Poindexter BB, Mendley SR, Delmore P, Sullivan JE, Autmizguine J, Lewandowski A, Harper B, Watt KM, Lewis KC, Capparelli EV, Benjamin DK Jr, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act - Pediatric Trials Network Administrative Core Committee. Use of opportunistic clinical data and a population pharmacokinetic model to support dosing of clindamycin for premature infants to adolescents. Clin Pharmacol Ther. 2014 Oct;96(4):429-37. doi: 10.1038/clpt.2014.134. Epub 2014 Jun 20.
- Gonzalez D, Delmore P, Bloom BT, Cotten CM, Poindexter BB, McGowan E, Shattuck K, Bradford KK, Smith PB, Cohen-Wolkowiez M, Morris M, Yin W, Benjamin DK Jr, Laughon MM. Clindamycin Pharmacokinetics and Safety in Preterm and Term Infants. Antimicrob Agents Chemother. 2016 Apr 22;60(5):2888-94. doi: 10.1128/AAC.03086-15. Print 2016 May.
- Gonzalez D, Melloni C, Poindexter BB, Yogev R, Atz AM, Sullivan JE, Mendley SR, Delmore P, Delinsky A, Zimmerman K, Lewandowski A, Harper B, Lewis KC, Benjamin DK Jr, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act--Pediatric Trials Network Administrative Core Committee. Simultaneous determination of trimethoprim and sulfamethoxazole in dried plasma and urine spots. Bioanalysis. 2015;7(9):1137-49. doi: 10.4155/bio.15.38.
- Autmizguine J, Melloni C, Hornik CP, Dallefeld S, Harper B, Yogev R, Sullivan JE, Atz AM, Al-Uzri A, Mendley S, Poindexter B, Mitchell J, Lewandowski A, Delmore P, Cohen-Wolkowiez M, Gonzalez D; the Pediatric Trials Network Steering Committee. Population Pharmacokinetics of Trimethoprim-Sulfamethoxazole in Infants and Children. Antimicrob Agents Chemother. 2017 Dec 21;62(1). pii: e01813-17. doi: 10.1128/AAC.01813-17. Print 2018 Jan.
- Dallefeld SH, Atz AM, Yogev R, Sullivan JE, Al-Uzri A, Mendley SR, Laughon M, Hornik CP, Melloni C, Harper B, Lewandowski A, Mitchell J, Wu H, Green TP, Cohen-Wolkowiez M. A pharmacokinetic model for amiodarone in infants developed from an opportunistic sampling trial and published literature data. J Pharmacokinet Pharmacodyn. 2018 Jun;45(3):419-430. doi: 10.1007/s10928-018-9576-y. Epub 2018 Feb 12.
- Hornik CP, Gonzalez D, van den Anker J, Atz AM, Yogev R, Poindexter BB, Ng KC, Delmore P, Harper BL, Melloni C, Lewandowski A, Gelber C, Cohen-Wolkowiez M, Lee JH; Pediatric Trial Network Steering Committee. Population Pharmacokinetics of Intramuscular and Intravenous Ketamine in Children. J Clin Pharmacol. 2018 Apr 20. doi: 10.1002/jcph.1116. [Epub ahead of print]
- Drolet BA, Boakye-Agyeman F, Harper B, Holland K, Lewandowski A, Stefanko N, Melloni C; Pediatric Trials Network Steering Committee (See Acknowledgments for a listing of committee members.). Systemic timolol exposure following topical application to infantile hemangiomas. J Am Acad Dermatol. 2020 Mar;82(3):733-736. doi: 10.1016/j.jaad.2019.02.029. Epub 2019 Feb 18.
- Hornik CP, Yogev R, Mourani PM, Watt KM, Sullivan JE, Atz AM, Speicher D, Al-Uzri A, Adu-Darko M, Payne EH, Gelber CE, Lin S, Harper B, Melloni C, Cohen-Wolkowiez M, Gonzalez D; Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee. Population Pharmacokinetics of Milrinone in Infants, Children, and Adolescents. J Clin Pharmacol. 2019 Dec;59(12):1606-1619. doi: 10.1002/jcph.1499. Epub 2019 Jul 17.
- Cohen-Wolkowiez M, Ouellet D, Smith PB, James LP, Ross A, Sullivan JE, Walsh MC, Zadell A, Newman N, White NR, Kashuba AD, Benjamin DK Jr. Population pharmacokinetics of metronidazole evaluated using scavenged samples from preterm infants. Antimicrob Agents Chemother. 2012 Apr;56(4):1828-37. doi: 10.1128/AAC.06071-11. Epub 2012 Jan 17.
- Cohen-Wolkowiez M, Benjamin DK Jr, Ross A, James LP, Sullivan JE, Walsh MC, Zadell A, Newman N, White NR, Kashuba AD, Ouellet D. Population pharmacokinetics of piperacillin using scavenged samples from preterm infants. Ther Drug Monit. 2012 Jun;34(3):312-9. doi: 10.1097/FTD.0b013e3182587665.
- Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001 Mar;69(3):89-95. Review.
- Kearns GL, Artman M. Functional Biomarkers: an Approach to Bridge Pharmacokinetics and Pharmacodynamics in Pediatric Clinical Trials. Curr Pharm Des. 2015;21(39):5636-42. Review.
- Husain A, Loehle JA, Hein DW. Clinical pharmacogenetics in pediatric patients. Pharmacogenomics. 2007 Oct;8(10):1403-11. Review.
- Zheng H, Webber S, Zeevi A, Schuetz E, Zhang J, Lamba J, Bowman P, Burckart GJ. The MDR1 polymorphisms at exons 21 and 26 predict steroid weaning in pediatric heart transplant patients. Hum Immunol. 2002 Sep;63(9):765-70.
- Odetola FO, Clark SJ, Freed GL, Bratton SL, Davis MM. A national survey of pediatric critical care resources in the United States. Pediatrics. 2005 Apr;115(4):e382-6.
- Watson RS, Crow SS, Hartman ME, Lacroix J, Odetola FO. Epidemiology and Outcomes of Pediatric Multiple Organ Dysfunction Syndrome. Pediatr Crit Care Med. 2017 Mar;18(3_suppl Suppl 1):S4-S16. doi: 10.1097/PCC.0000000000001047. Review.
- Typpo KV, Petersen NJ, Hallman DM, Markovitz BP, Mariscalco MM. Day 1 multiple organ dysfunction syndrome is associated with poor functional outcome and mortality in the pediatric intensive care unit. Pediatr Crit Care Med. 2009 Sep;10(5):562-70. doi: 10.1097/PCC.0b013e3181a64be1.
- Wang L, McGregor TL, Jones DP, Bridges BC, Fleming GM, Shirey-Rice J, McLemore MF, Chen L, Weitkamp A, Byrne DW, Van Driest SL. Electronic health record-based predictive models for acute kidney injury screening in pediatric inpatients. Pediatr Res. 2017 Sep;82(3):465-473. doi: 10.1038/pr.2017.116. Epub 2017 May 31.
- Kaddourah A, Basu RK, Bagshaw SM, Goldstein SL; AWARE Investigators. Epidemiology of Acute Kidney Injury in Critically Ill Children and Young Adults. N Engl J Med. 2017 Jan 5;376(1):11-20. doi: 10.1056/NEJMoa1611391. Epub 2016 Nov 18.
- Ricci Z, Goldstein SL. Pediatric Continuous Renal Replacement Therapy. Contrib Nephrol. 2016;187:121-30. doi: 10.1159/000442370. Epub 2016 Feb 8. Review.
- Hayes LW, Oster RA, Tofil NM, Tolwani AJ. Outcomes of critically ill children requiring continuous renal replacement therapy. J Crit Care. 2009 Sep;24(3):394-400. doi: 10.1016/j.jcrc.2008.12.017. Epub 2009 Mar 27.
- Nolin TD, Aronoff GR, Fissell WH, Jain L, Madabushi R, Reynolds K, Zhang L, Huang SM, Mehrotra R, Flessner MF, Leypoldt JK, Witcher JW, Zineh I, Archdeacon P, Roy-Chaudhury P, Goldstein SL; Kidney Health Initiative. Pharmacokinetic assessment in patients receiving continuous RRT: perspectives from the Kidney Health Initiative. Clin J Am Soc Nephrol. 2015 Jan 7;10(1):159-64. doi: 10.2215/CJN.05630614. Epub 2014 Sep 4.
- Buck ML. Pharmacokinetic changes during extracorporeal membrane oxygenation: implications for drug therapy of neonates. Clin Pharmacokinet. 2003;42(5):403-17. Review.
- Watt K, Li JS, Benjamin DK Jr, Cohen-Wolkowiez M. Pediatric cardiovascular drug dosing in critically ill children and extracorporeal membrane oxygenation. J Cardiovasc Pharmacol. 2011 Aug;58(2):126-32. doi: 10.1097/FJC.0b013e318213aac2. Review.
- Goldstein SL, Nolin TD. Lack of drug dosing guidelines for critically ill patients receiving continuous renal replacement therapy. Clin Pharmacol Ther. 2014 Aug;96(2):159-61. doi: 10.1038/clpt.2014.102. Epub 2014 May 8. Review.
- Lewis SJ, Mueller BA. Antibiotic dosing in critically ill patients receiving CRRT: underdosing is overprevalent. Semin Dial. 2014 Sep-Oct;27(5):441-5. doi: 10.1111/sdi.12203.
- Centers for Disease Control and Prevention (CDC). Improved national prevalence estimates for 18 selected major birth defects--United States, 1999-2001. MMWR Morb Mortal Wkly Rep. 2006 Jan 6;54(51):1301-5.
- Pritchard M, Reeves RH, Dierssen M, Patterson D, Gardiner KJ. Down syndrome and the genes of human chromosome 21: current knowledge and future potentials. Report on the Expert workshop on the biology of chromosome 21 genes: towards gene-phenotype correlations in Down syndrome. Washington D.C., September 28-October 1, 2007. Cytogenet Genome Res. 2008;121(1):67-77. doi: 10.1159/000124384. Epub 2008 May 7.
- Padmakumar B, Evans Jones LG, Sills JA. Is arthritis more common in children with Down syndrome? Rheumatology (Oxford). 2002 Oct;41(10):1191-3.
- Garré ML, Relling MV, Kalwinsky D, Dodge R, Crom WR, Abromowitch M, Pui CH, Evans WE. Pharmacokinetics and toxicity of methotrexate in children with Down syndrome and acute lymphocytic leukemia. J Pediatr. 1987 Oct;111(4):606-12.
- Peeters MA, Rethore MO, Lejeune J. In vivo folic acid supplementation partially corrects in vitro methotrexate toxicity in patients with Down syndrome. Br J Haematol. 1995 Mar;89(3):678-80.
- Jones JT, Talib N, Lovell D, Becker ML. Clinical Features and Treatment of Down Syndrome Arthropathy: Experience from Two US Tertiary Hospitals. Paediatr Drugs. 2019 Feb;21(1):33-39. doi: 10.1007/s40272-018-0322-0.
- Foley CM, Deely DA, MacDermott EJ, Killeen OG. Arthropathy of Down syndrome: an under-diagnosed inflammatory joint disease that warrants a name change. RMD Open. 2019 Jun 3;5(1):e000890. doi: 10.1136/rmdopen-2018-000890. eCollection 2019.
- Blatt J, Albo V, Prin W, Orlando S, Wollman M. Excessive chemotherapy-related myelotoxicity in children with Down syndrome and acute lymphoblastic leukaemia. Lancet. 1986 Oct 18;2(8512):914.
- Taub JW, Ge Y. Down syndrome, drug metabolism and chromosome 21. Pediatr Blood Cancer. 2005 Jan;44(1):33-9. Review.
- Uffmann M, Rasche M, Zimmermann M, von Neuhoff C, Creutzig U, Dworzak M, Scheffers L, Hasle H, Zwaan CM, Reinhardt D, Klusmann JH. Therapy reduction in patients with Down syndrome and myeloid leukemia: the international ML-DS 2006 trial. Blood. 2017 Jun 22;129(25):3314-3321. doi: 10.1182/blood-2017-01-765057. Epub 2017 Apr 11.
- Taub JW, Huang X, Matherly LH, Stout ML, Buck SA, Massey GV, Becton DL, Chang MN, Weinstein HJ, Ravindranath Y. Expression of chromosome 21-localized genes in acute myeloid leukemia: differences between Down syndrome and non-Down syndrome blast cells and relationship to in vitro sensitivity to cytosine arabinoside and daunorubicin. Blood. 1999 Aug 15;94(4):1393-400.
- Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999-2004. JAMA. 2006 Apr 5;295(13):1549-55.
- Sherwin J, Heath T, Watt K. Pharmacokinetics and Dosing of Anti-infective Drugs in Patients on Extracorporeal Membrane Oxygenation: A Review of the Current Literature. Clin Ther. 2016 Sep;38(9):1976-94. doi: 10.1016/j.clinthera.2016.07.169. Epub 2016 Aug 21. Review.
- Srinivasan V, Nadkarni VM, Helfaer MA, Carey SM, Berg RA; American Heart Association National Registry of Cardiopulmonary Resuscitation Investigators. Childhood obesity and survival after in-hospital pediatric cardiopulmonary resuscitation. Pediatrics. 2010 Mar;125(3):e481-8. doi: 10.1542/peds.2009-1324. Epub 2010 Feb 22.
|Same as current
|April 24, 2024
|April 24, 2024 (Final data collection date for primary outcome measure)
Participant is < 21 years of age and
- is receiving understudied drugs of interest (DOIs) per standard of care (SOC) as prescribed by their treating provider OR
is NOT receiving one or more of the study drugs of interest but is SARS-CoV-2 positive within 60 days prior to enrollment
2. Parent/ Legal Guardian/ Adult Participant can understand the consent process and is willing to provide informed consent/HIPAA
Participant has a known pregnancy
For participants receiving one or more of the study drugs of interest at the time of enrollment, DOI administration or PK sampling:
(Refer to DOI specific appendices for details on enrollment cohort specifications)
- Has had intermittent dialysis within previous 24 hours
- Has had a kidney transplant within previous 30 days
- Has had a liver transplant within previous 1 year
- Has had a stem cell transplant within previous 1 year
- Has had therapeutic hypothermia within previous 24 hours
- Has had plasmapheresis within the previous 24 hours
- Has a Ventricular Assist Device
- Has any condition which would make the participant, in the opinion of the investigator, unsuitable for the study
|Sexes Eligible for Study:
|up to 20 Years (Child, Adult)
|Canada, United States
|Studies a U.S. FDA-regulated Drug Product:
|Studies a U.S. FDA-regulated Device Product:
- The Emmes Company, LLC
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
||Duke Clinical Research Institute