Clinical trial NCT00854932: Neonatal Procalcitonin Intervention Study
Official title: Effect of Procalcitonin-guided Decision Making on Duration of Antibiotic Therapy in Suspected Neonatal Early-onset Sepsis: Multicenter Prospective Randomized Intervention Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Sepsis
Keywords: procalcitonin
sepsis
newborn
intervention study
Lead sponsor: Luzerner Kantonsspital
Sponsor class: OTHER
Collaborators: name: Kantonsspital Winterthur KSW
name: Triemli Hospital
name: Kantonsspital Graubuenden
name: Insel Gruppe AG, University Hospital Bern
name: Jeroen Bosch Ziekenhuis, s'-Hertogenbosch
name: Amsterdam UMC, location VUmc
name: Reinier de Graaf Groep
name: Erasmus Medical Center
name: Thomayer University Hospital
name: Flevo Ziekenhuis, Almere
name: Atrium Medisch Centrum, Heerlen
name: Ijssalland Ziekenhuis, Capelle aan den Ijssel
name: Sint Franciscus Gasthuis
name: Vlietland Ziekenhuis
name: McMaster University
name: St. Joseph's Healthcare Hamilton
First posted: 2009-03-03
Enrollment: 1600
Sex: ALL
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In neonates, clinical signs and symptoms associated with early-onset sepsis are non-specific and currently available tests have poor positive and negative predictive values. The investigators hypothesize that procalcitonin (PCT) has a reliable negative predictive values to allow a reduction in duration of empiric antibiotic therapy in suspected neonatal early-onset sepsis with unchanged outcome. This study is designed as a multi-center, prospective, randomized intervention trial. The duration of antibiotic therapy in the standard group is based on the attending physician's assessment of the probability of infection during hospitalisation. In the PCT group, if infection is considered to be unlikely or possible, antibiotic therapy is discontinued when two consecutive PCT values are within the normal range.

Detailed description: Detailed description according our pilot study (see reference). This trial is designed to exclude a difference in rate of re-infection or death greater than 2%. Assuming a 2% reinfection/death rate in each group, 770 patients are required for a power of 80% at alpha=0.05. To allow for some unevaluable cases 800 per group will be included. Based on the data of the pilot study (see reference), with a number of 770 per group a difference between mean antibiotic therapy durations of 10 hours can be detected at two-sided alpha of 0.05 with a power of 95%.

Eligibility criteria: Inclusion Criteria:

* Term and near term infants with a gestational age \> 34 weeks
* Suspected sepsis in the first 3 days of life requiring empiric antibiotic therapy
* Parental consent

Exclusion Criteria:

* Surgery in the first week of life
* Severe congenital malformations

Primary outcomes:
measure: The absolute reduction of the duration of antibiotic therapy with unchanged outcome
timeFrame: 1 month
Secondary outcomes:
measure: Duration of hospitalisation
timeFrame: 1 month
Other outcomes:
Locations:
city: Lucerne
country: Switzerland
facility: children's Hospital of Lucerne
Study officials:
affiliation: Kantonsspital Luzern, Switzerland
name: Martin Stocker, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stocker M, Fontana M, El Helou S, Wegscheider K, Berger TM. Use of procalcitonin-guided decision-making to shorten antibiotic therapy in suspected neonatal early-onset sepsis: prospective randomized intervention trial. Neonatology. 2010;97(2):165-74. doi: 10.1159/000241296. Epub 2009 Sep 24.
citation: Stocker M, Hop WC, van Rossum AM. Neonatal Procalcitonin Intervention Study (NeoPInS): Effect of Procalcitonin-guided decision making on duration of antibiotic therapy in suspected neonatal early-onset sepsis: A multi-centre randomized superiority and non-inferiority Intervention Study. BMC Pediatr. 2010 Dec 8;10:89. doi: 10.1186/1471-2431-10-89.
citation: Stocker M, Daunhawer I, van Herk W, El Helou S, Dutta S, Schuerman FABA, van den Tooren-de Groot RK, Wieringa JW, Janota J, van der Meer-Kappelle LH, Moonen R, Sie SD, de Vries E, Donker AE, Zimmerman U, Schlapbach LJ, de Mol AC, Hoffmann-Haringsma A, Roy M, Tomaske M, Kornelisse RF, van Gijsel J, Plotz FB, Wellmann S, Achten NB, Lehnick D, van Rossum AMC, Vogt JE. Machine Learning Used to Compare the Diagnostic Accuracy of Risk Factors, Clinical Signs and Biomarkers and to Develop a New Prediction Model for Neonatal Early-onset Sepsis. Pediatr Infect Dis J. 2022 Mar 1;41(3):248-254. doi: 10.1097/INF.0000000000003344.
citation: Stocker M, van Herk W, El Helou S, Dutta S, Fontana MS, Schuerman FABA, van den Tooren-de Groot RK, Wieringa JW, Janota J, van der Meer-Kappelle LH, Moonen R, Sie SD, de Vries E, Donker AE, Zimmerman U, Schlapbach LJ, de Mol AC, Hoffman-Haringsma A, Roy M, Tomaske M, Kornelisse RF, van Gijsel J, Visser EG, Willemsen SP, van Rossum AMC; NeoPInS Study Group. Procalcitonin-guided decision making for duration of antibiotic therapy in neonates with suspected early-onset sepsis: a multicentre, randomised controlled trial (NeoPIns). Lancet. 2017 Aug 26;390(10097):871-881. doi: 10.1016/S0140-6736(17)31444-7. Epub 2017 Jul 12.