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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01744730




Registration number
NCT01744730
Ethics application status
Date submitted
5/12/2012
Date registered
7/12/2012
Date last updated
29/11/2016

Titles & IDs
Public title
Safety and Pharmacokinetics of Clindamycin in Pediatric Subjects With BMI = 85th Percentile
Scientific title
Safety and Pharmacokinetics of Multiple-Dose Intravenous and Oral Clindamycin in Pediatric Subjects With BMI = 85th Percentile (NICHD): CLIN01
Secondary ID [1] 0 0
HHSN275201000003I
Secondary ID [2] 0 0
Pro00041855
Universal Trial Number (UTN)
Trial acronym
CLIN01
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bacterial Infections 0 0
Obesity 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Clindamycin

Active comparator: Clindamycin IV-ages 2 to 11 Years Old (BMI 85-95th Percentile) - Clindamycin IV: Children ages 2 to 11 years old with BMI 85th to 95th percentile. Their schedule of IV Clindamycin administration included 30-40 mg/kg/day dosed every 6 or every 8 hours with a maximum daily dose of 2.7 grams/day. Dosing greater than 2.7g/day was allowed for children receiving clindamycin as part of clinical care.

Active comparator: Clindamycin IV-ages 2 to 11 Years Old (BMI Greater Than 95th) - Clindamycin IV: Children ages 2 to 11 years old with BMI greater than 95th percentile. Their schedule of IV Clindamycin administration included 30-40 mg/kg/day dosed every 6 or every 8 hours with a maximum daily dose of 2.7 grams/day. Dosing greater than 2.7g/day was allowed for children receiving clindamycin as part of clinical care.

Active comparator: Clinidamycin IV-ages 12 to 17 (BMI 85-95th Percentile) - Clindamycin IV: Children ages 12 to 17 years old with BMI 85th to 95th percentile. Their schedule of IV Clindamycin administration included 30-40 mg/kg/day dosed every 6 or every 8 hours with a maximum daily dose of 2.7 grams/day. Dosing greater than 2.7g/day was allowed for children receiving clindamycin as part of clinical care.

Active comparator: Clindamycin IV-ages 12 to 17 (BMI Greater Than 95th) - Clindamycin IV: Children ages 12 to 17 years old with BMI greater than 95th percentile. Their schedule of IV Clindamycin administration included 30-40 mg/kg/day dosed every 6 or every 8 hours with a maximum daily dose of 2.7 grams/day. Dosing greater than 2.7g/day was allowed for children receiving clindamycin as part of clinical care.


Treatment: Drugs: Clindamycin
Schedule includes 30-40 mg/kg/day dosed every 6 or every 8 hours with a maximum daily dose of 2.7 grams/day. Dosing greater than 2.7g/day will be allowed for children receiving clindamycin as part of clinical care.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Knee Injury and Osteoarthritis Outcome Score (KOOS) activities of daily living (ADL) sub-score change from baseline.
Timepoint [1] 0 0
One year or later (approximately 304 days or later)
Primary outcome [2] 0 0
Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin.
Timepoint [2] 0 0
After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6).
Primary outcome [3] 0 0
Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin.
Timepoint [3] 0 0
After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).
Primary outcome [4] 0 0
Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin.
Timepoint [4] 0 0
After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).
Primary outcome [5] 0 0
PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin.
Timepoint [5] 0 0
After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).
Primary outcome [6] 0 0
PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin.
Timepoint [6] 0 0
After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).
Secondary outcome [1] 0 0
Patient Reported Outcome: Oxford Knee Score (OKS)
Timepoint [1] 0 0
Pre-op (-90 to -1 days before surgery), < 1 year (1 to 303 days), minimum 1 year (304 to 668 days), minimum 2 year (669 to 1763 days)
Secondary outcome [2] 0 0
Patient Reported Outcome: Pre-surgical/Post-surgical Patient's Knee Implant Performance (PKIP)
Timepoint [2] 0 0
Pre-op (-90 to -1 days before surgery), < 1 year (1 to 303 days), minimum 1 year (304 to 668 days), minimum 2 year (669 to 1763 days)
Secondary outcome [3] 0 0
Patient Report Outcome: EuroQol 5D 3L questionnaire (EQ-5D-3L)
Timepoint [3] 0 0
Pre-op (-90 to -1 days before surgery), < 1 year (1 to 303 days), minimum 1 year (304 to 668 days), minimum 2 year (669 to 1763 days)
Secondary outcome [4] 0 0
Type and Frequency of Adverse Events (AEs) for all enrolled subjects
Timepoint [4] 0 0
< 1 year (1 to 303 days), minimum 1 year (304 to 668 days), minimum 2 year (669 to 1763 days)
Secondary outcome [5] 0 0
Evaluate primary cemented fixation through zonal radiographic analysis post-operatively
Timepoint [5] 0 0
minimum 1 year (304 to 668 days), minimum 2 year (669 to 1763 days)
Secondary outcome [6] 0 0
Incidence of post-operative anterior knee pain and symptomatic/asymptomatic crepitus
Timepoint [6] 0 0
Pre-op (-90 to -1 days before surgery), < 1 year (1 to 303 days), minimum 1 year (304 to 668 days), minimum 2 year (669 to 1763 days)
Secondary outcome [7] 0 0
Evaluate surgeon learning curve on clinical and functional outcomes
Timepoint [7] 0 0
< 1 year (1 to 303 days), minimum 1 year (304 to 668 days), minimum 2 year (669 to 1763 days)
Secondary outcome [8] 0 0
Evaluate the impact of ligament balancing surgical technique on functional performance
Timepoint [8] 0 0
Operatively (Day 0 - Date of Surgery)
Secondary outcome [9] 0 0
Psychometric Properties of the Patient Knee Implant Performance (PKIP)questionnaire
Timepoint [9] 0 0
Pre-op (-90 to -1 days before surgery), < 1 year (1 to 303 days), minimum 1 year (304 to 668 days), minimum 2 year (669 to 1763 days)
Secondary outcome [10] 0 0
Evaluate the functional outcome of patella resurfacing and non-resurfacing
Timepoint [10] 0 0
< 1 year (1 to 303 days), minimum 1 year (304 to 668 days), minimum 2 year (669 to 1763 days)
Secondary outcome [11] 0 0
Evaluate changes in femoral component and tibial component alignment
Timepoint [11] 0 0
< 1 year (1 to 303 days), minimum 1 year (304 to 668 days), minimum 2 year (669 to 1763 days)

Eligibility
Key inclusion criteria
* 2 years - < 18 years of age at the time of first dose of study drug
* Suspected or confirmed infection OR receiving IV clindamycin per routine care
* Negative serum pregnancy test (if female and has reached menarche) within 24 hours of first dose of study drug and agreement to practice appropriate contraceptive measures, including abstinence, from the time of the initial pregnancy test through the last dose of study drug
* BMI = 85th percentile for age and sex, based on Centers for Disease Control (CDC) recommendations
* Signed informed consent/Health Insurance Portability and Accountability Act (HIPAA) documents by the parent/legal guardian and assent (if applicable)
Minimum age
2 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* The following apply only to those who are NOT already receiving clindamycin per routine care:

1. History of hypersensitivity or allergic reaction to clindamycin or lincomycin
2. History of C. difficile colitis with previous administration of clindamycin
3. Aspartate aminotransferase (AST) > 120 units/L
4. Alanine aminotransferase (ALT) > 210 units/L
5. Total bilirubin > 3 mg/dL
6. Serum creatinine > 2 mg/dL
7. Receiving a neuromuscular blocker as part of their therapy
* Previous participation in the study
* Subject is on prohibited medication or herbal product (see Appendix II)
* Subject is receiving extracorporeal life support (ECLS)
* Subject is post-cardiac bypass (within 24 hours)
* Subject on inotropes/pressors
* Any other condition or chronic illness that, in the opinion of the principal investigator, makes participation unadvised or unsafe

Study design
Purpose of the study
Other
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2014
Sample size
Target
Accrual to date
Final
22
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Illinois
Country [2] 0 0
United States of America
State/province [2] 0 0
Kansas
Country [3] 0 0
United States of America
State/province [3] 0 0
Kentucky
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
California
Country [6] 0 0
United States of America
State/province [6] 0 0
Colorado
Country [7] 0 0
United States of America
State/province [7] 0 0
Nevada
Country [8] 0 0
United States of America
State/province [8] 0 0
New Hampshire

Funding & Sponsors
Primary sponsor type
Other
Name
Phillip Brian Smith
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
The Emmes Company, LLC
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to better understand how clindamycin works in children who fall in the 85th percentile or higher for body mass index (BMI - a ratio of weight to height). The results of the study will help better understand if children in higher BMI ranges process the medication differently and whether dosing should be adjusted in these children.
Trial website
https://clinicaltrials.gov/study/NCT01744730
Trial related presentations / publications
Gerber JS, Coffin SE, Smathers SA, Zaoutis TE. Trends in the incidence of methicillin-resistant Staphylococcus aureus infection in children's hospitals in the United States. Clin Infect Dis. 2009 Jul 1;49(1):65-71. doi: 10.1086/599348.
Herigon JC, Hersh AL, Gerber JS, Zaoutis TE, Newland JG. Antibiotic management of Staphylococcus aureus infections in US children's hospitals, 1999-2008. Pediatrics. 2010 Jun;125(6):e1294-300. doi: 10.1542/peds.2009-2867. Epub 2010 May 17.
Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity and trends in body mass index among US children and adolescents, 1999-2010. JAMA. 2012 Feb 1;307(5):483-90. doi: 10.1001/jama.2012.40. Epub 2012 Jan 17.
Kasten MJ. Clindamycin, metronidazole, and chloramphenicol. Mayo Clin Proc. 1999 Aug;74(8):825-33. doi: 10.4065/74.8.825.
Pai MP, Bearden DT. Antimicrobial dosing considerations in obese adult patients. Pharmacotherapy. 2007 Aug;27(8):1081-91. doi: 10.1592/phco.27.8.1081.
Bearden DT, Rodvold KA. Dosage adjustments for antibacterials in obese patients: applying clinical pharmacokinetics. Clin Pharmacokinet. 2000 May;38(5):415-26. doi: 10.2165/00003088-200038050-00003.
Falagas ME, Kompoti M. Obesity and infection. Lancet Infect Dis. 2006 Jul;6(7):438-46. doi: 10.1016/S1473-3099(06)70523-0.
Reed MD. Reversing the myths obstructing the determination of optimal age- and disease-based drug dosing in pediatrics. J Pediatr Pharmacol Ther. 2011 Jan;16(1):4-13.
Jacobs MR. How can we predict bacterial eradication? Int J Infect Dis. 2003 Mar;7 Suppl 1:S13-20. doi: 10.1016/s1201-9712(03)90066-x.
Bradley JS, Garonzik SM, Forrest A, Bhavnani SM. Pharmacokinetics, pharmacodynamics, and Monte Carlo simulation: selecting the best antimicrobial dose to treat an infection. Pediatr Infect Dis J. 2010 Nov;29(11):1043-6. doi: 10.1097/INF.0b013e3181f42a53. No abstract available.
Bell MJ, Shackelford P, Smith R, Schroeder K. Pharmacokinetics of clindamycin phosphate in the first year of life. J Pediatr. 1984 Sep;105(3):482-6. doi: 10.1016/s0022-3476(84)80033-5.
Koren G, Zarfin Y, Maresky D, Spiro TE, MacLeod SM. Pharmacokinetics of intravenous clindamycin in newborn infants. Pediatr Pharmacol (New York). 1986;5(4):287-92.
DeHaan RM, Schellenberg D. Clindamycin palmitate flavored granules. Multidose tolerance, absorption, and urinary excretion study in healthy children. J Clin Pharmacol New Drugs. 1972 Feb-Mar;12(2):74-83. doi: 10.1002/j.1552-4604.1972.tb00149.x. No abstract available.
DeHaan RM, Metzler CM, Schellenberg D, Vandenbosch WD. Pharmacokinetic studies of clindamycin phosphate. J Clin Pharmacol. 1973 May-Jun;13(5):190-209. doi: 10.1002/j.1552-4604.1973.tb00208.x. No abstract available.
del Carmen Carrasco-Portugal M, Lujan M, Flores-Murrieta FJ. Evaluation of gender in the oral pharmacokinetics of clindamycin in humans. Biopharm Drug Dispos. 2008 Oct;29(7):427-30. doi: 10.1002/bdd.624.
DeHaan RM, Metzler CM, Schellenberg D, VandenBosch WD, Masson EL. Pharmacokinetic studies of clindamycin hydrochloride in humans. Int J Clin Pharmacol. 1972 Jun;6(2):105-19. No abstract available.
Townsend RJ, Baker RP. Pharmacokinetic comparison of three clindamycin phosphate dosing schedules. Drug Intell Clin Pharm. 1987 Mar;21(3):279-81. doi: 10.1177/106002808702100310.
Wynalda MA, Hutzler JM, Koets MD, Podoll T, Wienkers LC. In vitro metabolism of clindamycin in human liver and intestinal microsomes. Drug Metab Dispos. 2003 Jul;31(7):878-87. doi: 10.1124/dmd.31.7.878.
Green B, Duffull S. Caution when lean body weight is used as a size descriptor for obese subjects. Clin Pharmacol Ther. 2002 Dec;72(6):743-4. doi: 10.1067/mcp.2002.129306. No abstract available.
Erstad BL. Which weight for weight-based dosage regimens in obese patients? Am J Health Syst Pharm. 2002 Nov 1;59(21):2105-10. doi: 10.1093/ajhp/59.21.2105. No abstract available.
Weiss M. How does obesity affect residence time dispersion and the shape of drug disposition curves? Thiopental as an example. J Pharmacokinet Pharmacodyn. 2008 Jun;35(3):325-36. doi: 10.1007/s10928-008-9090-8. Epub 2008 May 9.
Berezhkovskiy LM. On the accuracy of estimation of basic pharmacokinetic parameters by the traditional noncompartmental equations and the prediction of the steady-state volume of distribution in obese patients based upon data derived from normal subjects. J Pharm Sci. 2011 Jun;100(6):2482-97. doi: 10.1002/jps.22444. Epub 2011 Jan 19.
Morrish GA, Pai MP, Green B. The effects of obesity on drug pharmacokinetics in humans. Expert Opin Drug Metab Toxicol. 2011 Jun;7(6):697-706. doi: 10.1517/17425255.2011.570331. Epub 2011 Mar 22.
Leykin Y, Miotto L, Pellis T. Pharmacokinetic considerations in the obese. Best Pract Res Clin Anaesthesiol. 2011 Mar;25(1):27-36. doi: 10.1016/j.bpa.2010.12.002.
Weinstein AJ, Gibbs RS, Gallagher M. Placental transfer of clindamycin and gentamicin in term pregnancy. Am J Obstet Gynecol. 1976 Apr 1;124(7):688-91. doi: 10.1016/s0002-9378(16)33336-1.
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.
Gatti G, Flaherty J, Bubp J, White J, Borin M, Gambertoglio J. Comparative study of bioavailabilities and pharmacokinetics of clindamycin in healthy volunteers and patients with AIDS. Antimicrob Agents Chemother. 1993 May;37(5):1137-43. doi: 10.1128/AAC.37.5.1137.
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
P. Brian Smith, MD, MHS, MPH
Address 0 0
Duke Medical Center/Duke Clinical Research Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01744730