Neonatal Procalcitonin Intervention Study (NeoPInS)

Effect of Procalcitonin-guided Decision Making on Duration of Antibiotic Therapy in Suspected Neonatal Early-onset Sepsis: Multicenter Prospective Randomized Intervention Study

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.

Study Overview

• Status: Unknown
• Conditions: Sepsis
• Intervention / Treatment: Other: Procalcitonin-guided decision making

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%.

• Study Type: Interventional
• Enrollment (Anticipated): 1600
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Lucerne, Switzerland, 6000
    • children's Hospital of Lucerne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 days (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: PCT group; 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.Antibiotic therapy can be continued despite fulfilled criteria at the discretion of the attending physician. These divesions from the stopping rules will be reported for further analysis.	Other: Procalcitonin-guided decision making; In the PCT group, if infection is considered to be unlikely or possible, antibiotic therapy is discontinued when two consecutive PDT values are within the normal range.; Other Names: Procalcitonin-guided duration of antibiotic therapy
NO_INTERVENTION: Standard group; The duration of antibiotic treatment in the standard group is based on the attending physician's assessment of the risk of classification: infection unlikely for 36-72 hours, infection possible for 5-7 days, infection probable of proven for 7-21 days depending on clinical course, laboratory values and positive cultures.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The absolute reduction of the duration of antibiotic therapy with unchanged outcome	Unchanged outcome = proportion of infants with a recurrence of infection requiering additional courses of antibiotic therapy within 72 hours after ending antibiotic therapy and/or death in the first month of life	1 month

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of hospitalisation	1 month

Collaborators and Investigators

• Sponsor: Luzerner Kantonsspital
• Collaborators: St. Joseph's Healthcare Hamilton; University Hospital Inselspital, Berne; Erasmus Medical Center; McMaster University; Amsterdam UMC, location VUmc; Triemli Hospital; Kantonsspital Winterthur KSW; Vlietland Ziekenhuis; Sint Franciscus Gasthuis; Thomayer University Hospital; Kantonsspital Graubuenden; Jeroen Bosch Ziekenhuis, s'-Hertogenbosch; Reinier de Graaf Gasthuis Delft; Flevo Ziekenhuis, Almere; Atrium Medisch Centrum, Heerlen; Ijssalland Ziekenhuis, Capelle aan den Ijssel
• Investigators: Principal Investigator: Martin Stocker, MD, Kantonsspital Luzern, Switzerland

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (ACTUAL): May 1, 2015
• Study Completion (ANTICIPATED): August 1, 2016

Study Registration Dates

• First Submitted: March 2, 2009
• First Submitted That Met QC Criteria: March 2, 2009
• First Posted (ESTIMATE): March 3, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): March 8, 2016
• Last Update Submitted That Met QC Criteria: March 4, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: sepsis; procalcitonin; newborn; intervention study
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: NeoPInS