Clinical trial NCT02048163: Intermittent Versus Continuous Infusion Meropenem in Cystic Fibrosis
Official title: A Comparison of the Effect of Intermittent and Continuous Infusion of Meropenem on the Prevalence of Nausea in Pediatric Cystic Fibrosis Patients
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Cystic Fibrosis
Keywords: Meropenem
Nausea
Pharmacokinetics
Lead sponsor: Dayton Children's Hospital
Sponsor class: OTHER
First posted: 2014-01-29
Enrollment: 0
Sex: ALL
Minimum age (years): 7
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_CROSSOVER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Male and female patients with cystic fibrosis ages 7 to 21 who are admitted to Dayton Children's Hospital and who will receive meropenem as part of their treatment regimen.

Brief summary: The purpose of this study is to compare the incidence of nausea and vomiting following short intermittent versus prolonged intermittent infusion of meropenem.

Detailed description: 1. To assess the number of episodes of emesis following both short and prolonged intermittent infusion of meropenem.
2. To assess the number of episodes of emesis corresponding to the peak serum concentration of meropenem.
3. To assess the number of episodes of emesis corresponding to the area under the meropenem serum concentration time curve.
4. To assess reported nausea, measured through administered dosages of anti-nausea medication, following both short and prolonged intermittent infusion of meropenem.
5. To assess reported nausea, measured through administered doses of anti-nausea medication, corresponding to peak concentrations of meropenem.
6. To assess reported nausea, measured through administered dosages of anti-nausea medication, corresponding to the area under the serum concentration time curve
7. To assess reported nausea, measured through patient-reported nausea measured using pictorial scales of severity of nausea in pediatric patients, following both short and prolonged intermittent infusion of meropenem.
8. To assess reported nausea, measured through patient-reported nausea measured using pictorial scales of severity corresponding to the peak serum concentrations of meropenem.
9. To assess reported nausea, measured through patient-reported nausea measured using pictorial scales of severity corresponding to the area under the meropenem serum concentration time curve.

Eligibility criteria: Inclusion Criteria:

1. Be an admitted patient at Dayton Children's Hospital.
2. Between 7 and 21 years of age.
3. Have a documented CF diagnosis with one or more of the following clinical features:

   1. Sweat chloride \> 60 mEq/liter as determined by quantitative pilocarpine iontophoresis test (QPIT).
   2. Two mutations (well characterized) in the cystic fibrosis transmembrane conductive regulator (CTFR) gene.
   3. Abnormal nasal potential difference.
4. Based on Hankinson/NHanes III criteria, are able to elicit an FEV1 \> 25% but with \< 95% predicted value when admitted.
5. Sputum or throat swab specimen positive for P. aeruginosa and have a history of at least one additional sputum culture positive for P. aeruginosa within the last 12 months.
6. Are able to perform an acceptable spirometry session (defined as 3 acceptable or usable efforts per ATS/ERS criteria upon admission).
7. Have not smoked tobacco within 28 days prior to Visit 1 and agree not to smoke for the duration of the study.
8. Are able to and have given written informed consent (if they are adults) or assent in combination with consent of their legal representative(s) (if they are minors) in a manner approved by the Institutional Review Board.
9. Patient is experiencing symptoms of CF exacerbation of CF: with any 4 of the following 12 signs or symptoms:

   * Change in sputum;
   * New or increased hemoptysis;
   * Increased cough;
   * Increased dyspnea;
   * Malaise, fatigue or lethargy;
   * Temperature above 38°C;
   * Anorexia or weight loss;
   * Sinus pain or tenderness;
   * Change in sinus discharge;
   * Change in physical examination of the chest;
   * Decrease in pulmonary function by 10 percent or more from a previously recorded value;
   * Radiographic changes indicative of pulmonary infection.

Exclusion Criteria:

1. History of hypersensitivity or intolerance to meropenem.
2. History of hypersensitivity or intolerance to granisetron.
3. Are pregnant, breastfeeding, or unwilling to practice a highly effective method of birth control or abstinence during participation in the study.

Primary outcomes:
measure: Compare indices of nausea following both prolonged intermittent and short intermittent infusions of meropenem
timeFrame: Nausea will be assessed while patient is receiving 4 days of prolonged intermittent infusion and 4 days of short intermittent infusion.
Secondary outcomes:
measure: Compare pharmacokinetic data to indices of nausea.
timeFrame: Pharmacokinetic data will be obtained following the third, fourth, or fifth dose of meropenem administered during of each arm of the study. Peak serum concentration and area under the serum concentration time curve will be compared to nausea indices.
Other outcomes:
Locations:
city: Dayton
country: United States
facility: Dayton Children's Hospital
state: Ohio
Study officials:
affiliation: Dayton Children's Hospital
name: Pat Christoff, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Prescott WA Jr, Gentile AE, Nagel JL, Pettit RS. Continuous-infusion antipseudomonal Beta-lactam therapy in patients with cystic fibrosis. P T. 2011 Nov;36(11):723-63.
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citation: Lodise TP, Lomaestro BM, Drusano GL; Society of Infectious Diseases Pharmacists. Application of antimicrobial pharmacodynamic concepts into clinical practice: focus on beta-lactam antibiotics: insights from the Society of Infectious Diseases Pharmacists. Pharmacotherapy. 2006 Sep;26(9):1320-32. doi: 10.1592/phco.26.9.1320.
citation: Du X, Li C, Kuti JL, Nightingale CH, Nicolau DP. Population pharmacokinetics and pharmacodynamics of meropenem in pediatric patients. J Clin Pharmacol. 2006 Jan;46(1):69-75. doi: 10.1177/0091270005283283.
citation: Legrand T, Chhun S, Rey E, Blanchet B, Zahar JR, Lanternier F, Pons G, Jullien V. Simultaneous determination of three carbapenem antibiotics in plasma by HPLC with ultraviolet detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Nov 15;875(2):551-6. doi: 10.1016/j.jchromb.2008.09.020. Epub 2008 Sep 25.
citation: Blumer JL, Reed MD, Kearns GL, Jacobs RF, Gooch WM 3rd, Yogev R, Willims K, Ewing BJ. Sequential, single-dose pharmacokinetic evaluation of meropenem in hospitalized infants and children. Antimicrob Agents Chemother. 1995 Aug;39(8):1721-5. doi: 10.1128/AAC.39.8.1721.