TINN Pharmacokinetics (PK) Study Treat Infections iN Neonates (TINN-PK)

Phase I, Open-label Study to Evaluate the Pharmacokinetics and Tolerability of Ciprofloxacin in Neonates With Suspected or Proven Gram Negative Infection

Phase I, open-label study to evaluate the pharmacokinetics, tolerability and short-term safety of ciprofloxacin in neonates with suspected (or proven) Gram Negative infection. Objectives: To evaluate the multiple-dose pharmacokinetics of ciprofloxacin in neonates and young infants (24 - 52 weeks postmenstrual age) with suspected or proven Gram Negative infection.

To evaluate the tolerability and describe short-term safety of ciprofloxacin in neonates and young infants with suspected (or proven) Gram Negative infection.

To describe the clinical outcomes of neonates treated with ciprofloxacin

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics of Ciprofloxacin in Neonates
• Intervention / Treatment: Procedure: Collection of biological samples

Detailed Description

This study is part of TINN 'Treat Infections in Neonates' a comprehensive project that is evaluating the safety of ciprofloxacin and how it is tolerated by neonates. Ciprofloxacin is an antibiotic that has been used for many years in newborn babies and infants less than 3 months old to treat bacteria that are resistant to other antibiotics. Ciprofloxacin is unlicensed for this age group. The European Medicines Agency and WHO have prioritised research about this drug. The TINN consortium aims to conduct the work required for a license (marketing authorization) in newborn babies and infants less than 3 months old. The aim of this study is to describe how newborn babies and young infants deal with this medicine. Blood samples will be taken at the beginning of the course of antibiotics and at the end. A minimal amount of blood will be required (less than half a teaspoon) in total and collected by staff experienced in blood sampling from neonates in a way that causes the least disruption to the baby. The levels of ciprofloxacin in the blood will be measured. The levels will be used to work out how quickly the body gets rid of the medicine. This will allow recommendations about the best dose and how often the medicine should be given.

We aim to recruit 50 neonates and infants under the age of 3 months who have been prescribed Ciprofloxacin as inpatients for suspected or proven infection. They will be recruited over 2 years from the neonatal unit at Liverpool Women's NHS Foundation Trust and Alder Hey Children's NHS Foundation Trust. Consent will be requested for babies to have more detailed investigation to see if there if genetic factors affect the way the body handles ciprofloxacin.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Merseyside
    • Liverpool, Merseyside, United Kingdom, L12 2AP
      • Alder Hey Children's NHS Foundation Trust
    • Liverpool, Merseyside, United Kingdom, L8 7SS
      • Liverpool Women's NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 11 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Receiving ciprofloxacin following clinical decision by attending physician

Exclusion Criteria:

• Likely not to survive 48 hours in the judgement of attending physician
• Ciprofloxacin commenced before 5th day of life

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Pharmacokinetics of ciprofloxacin; Patients receiving ciprofloxacin following clinical decision by attending physician	Procedure: Collection of biological samples; Sparse blood samples (n=2 or 3 depending on weight) will be drawn on day 1 and day 5- 7 (or last day of treatment if the course is completed before day 7). Monitoring of adverse events DNA for pharmacogenetics (scavenged clinical samples or buccal) CSF (if required clinically) Faeces

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ciprofloxacin plasma concentration and population pharmacokinetic (PK) parameters	Ciprofloxacin plasma concentration and population pharmacokinetic (PK) parameters [maximum concentration, clearance, area under the curve (0-tau)], their relationship with selected covariates their interindividual variability (CV%). Covariate analysis will include postmenstrual age, gestational age, postnatal age, weight, and serum creatinine	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK variables	PK variables, including apparent volume of distribution and half life.	6 weeks
Tolerability	Withdrawal due to lack of tolerability	6 weeks
Safety	Adverse events (AEs) and serious adverse events (SAEs).	6 Weeks
Clinical/microbiological outcomes	Outcome of treatment episodes (clinical and microbiological)	6 Weeks

Collaborators and Investigators

• Sponsor: Liverpool Women's NHS Foundation Trust
• Collaborators: University of Liverpool
• Investigators: Principal Investigator: Mark A Turner, MD, University of Liverpool/Liverpool Women's Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: March 17, 2011
• First Submitted That Met QC Criteria: March 18, 2011
• First Posted (Estimate): March 21, 2011

Study Record Updates

• Last Update Posted (Estimate): October 12, 2015
• Last Update Submitted That Met QC Criteria: October 9, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Neonates; Ciprofloxacin; Gram negative infection
• Additional Relevant MeSH Terms: Infections
• Other Study ID Numbers: LWH0852; 2010-019955-23 (EudraCT Number)