PRedicting OutcomeS in Preterm nEonates With thromboCyTopenia (PROSPECT)

September 2, 2025 updated by: Hilde van der Staaij, MD, Leiden University Medical Center

Sequential Predictions Under Repeated Interventions: Estimating the Risk of Major Bleeding or Death With and Without Prophylactic Platelet Transfusion in Thrombocytopenic Neonates.

Preterm neonates often receive platelet transfusions when their platelet count is low to prevent bleeding. However, it is currently unclear which infants benefit from such transfusions. A recent randomized controlled trial (PlaNeT-2/MATISSE trial) showed that the higher platelet count threshold for transfusion was associated with a higher risk of major bleeding or death. Current transfusion protocols are based only on platelet count thresholds. However, neonates with similar platelet counts may have different bleeding risks due to varying clinical conditions. There is an important unmet medical need to identify which neonates with low platelet counts (i.e., severe thrombocytopenia) will benefit from a transfusion. Ideally, clinicians would be able to repeatedly predict a neonate's risk of major bleeding or death with and without giving a platelet transfusion, taking into account the neonate's clinical condition at that particular time. Obtaining personalized risk estimates under specific treatment strategies, with updated predictions at each new treatment decision moment, is called 'sequential prediction under interventions'. The investigators set up an international multicenter observational cohort study to develop a model to predict major bleeding or death with and without platelet transfusion at any time point during the first week after the onset of severe thrombocytopenia. This model is designed to support platelet transfusion decisions in the NICU and may help clinicians balance the benefits and harms of platelet transfusion based on updated characteristics of the neonate at the time of prediction.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Main objective: To develop a sequential interventional prediction model to support transfusion decisions by predicting the risk of major bleeding or death with and without giving a platelet transfusion to neonates with severe thrombocytopenia (i.e., platelet count below 50x10^9/L), conditional on their characteristics present at the moment of prediction.

Study design: Multicenter international observational cohort study.

Study population: Neonates with a gestational age below 34 weeks and at least one platelet count below 50x10^9/L, admitted to a neonatal intensive care unit (NICU) between January 1st 2017 and January 1st 2022.

Main study endpoint: Major bleeding or mortality during NICU admission

Assessments: Only routine care data will be collected. This includes platelet counts and transfusions, cranial (head) ultrasounds and other information on bleeding, and multiple clinical variables.

Statistical analyses: Development of a sequential prediction model under interventions using the cloning-censoring-weighting approach with inverse probability weighting. Validation of the model in a separate cohort of preterm neonates with severe thrombocytopenia.

Study Type

Observational

Enrollment (Actual)

1042

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
    • Metropolregion Berlin-Brandenburg
      • Berlin, Metropolregion Berlin-Brandenburg, Germany, 10117
        • Charité - Universitätsmedizin Berlin
  • Netherlands
    • Gelderland
      • Nijmegen, Gelderland, Netherlands, 6525 GA
        • Radboud University Medical Center, Amalia Children's hospital
    • Limburg
      • Maastricht, Limburg, Netherlands, 6229 HX
        • Maastricht University Medical Center, MosaKids
    • North Brabant
      • Veldhoven, North Brabant, Netherlands, 5504 DB
        • Maxima Medical Center
    • North Holland
      • Amsterdam, North Holland, Netherlands, 1081 HV
        • Amsterdam University Medical Center, Emma Children's hospital, location VUmc
      • Amsterdam, North Holland, Netherlands, 1105 AZ
        • Amsterdam University Medical Center, Emma Children's hospital, location AMC
    • Overijssel
      • Zwolle, Overijssel, Netherlands, 8025 AB
        • Isala Clinics
    • Provincie Groningen
      • Groningen, Provincie Groningen, Netherlands, 9713 GZ
        • University Medical Center Groningen, Beatrix Children's hospital
    • South Holland
      • Leiden, South Holland, Netherlands, 2333 ZA
        • Leiden University Medical Center, Willem Alexander Children's hospital
      • Rotterdam, South Holland, Netherlands, 3015 CN
        • Erasmus University Medical Center, Sophia pediatric hospital
    • Utrecht
      • Utrecht, Utrecht, Netherlands, 3584 EA
        • University Medical Center Utrecht, Wilhelmina Children's hospital
  • Sweden
    • Södermanland and Uppland
      • Stockholm, Södermanland and Uppland, Sweden, 171 76
        • Karolinska University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Neonates with a gestational age below 34 weeks and at least one platelet count below 50x10^9/L, admitted to a NICU between January 1st, 2017 and January 1st, 2022.

Description

Inclusion Criteria:

  1. Gestational age at birth <34 weeks;
  2. At least one platelet count <50x109/L;
  3. Admission to a participating tertiary care NICU, including postnatal transfers, between January 1st, 2017 and January 1st, 2022.

Exclusion Criteria:

  1. A severe congenital malformation;
  2. Only spurious platelet counts <50x109/L (e.g. clots in the sample, or a very rapid recovery to a normal platelet count without platelet transfusion);
  3. Only platelet counts <50x109/L in the context of exchange transfusion;
  4. Major intracranial bleeding prior to the onset of severe thrombocytopenia. Neonates with major bleeding after the end of follow-up will not be excluded, but will be recorded as having had no major bleeding during the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Neonates with severe thrombocytopenia
Neonates with a gestational age below 34 weeks and at least one platelet count below 50x10^9/L, who were admitted to a NICU between January 1st, 2017 and January 1st, 2022.
Drug: Platelets
Observational data: all platelet transfusions recorded in routine care medical file data.
Other Names:
  • Platelet transfusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
A composite of major bleeding or death during NICU admission is the primary outcome. Neonates who first had a major bleeding and then died reach the endpoint at the time of the major bleeding.
Time Frame: From onset of severe thrombocytopenia until one week thereafter. The risk of major bleeding or death is predicted within 3 days and within 14 days from each moment of prediction during this time frame.

The investigators defined major bleeding as either one of the following:

  1. Intraventricular hemorrhage (IVH) grade 3 or IVH of any grade in combination with parenchymal involvement (according to the Volpe grading system);
  2. Parenchymal hemorrhage (without IVH) or cerebellar hemorrhage (>4 mm visible on cranial ultrasound, not if ≤4 mm visible on MRI only);
  3. Pulmonary hemorrhage, defined as a fresh bleed from the trachea requiring intubation or ventilation, or a fresh bleed from the tube requiring increased ventilatory requirements;

  4. Any type of severe hemorrhage, including gastrointestinal bleeding, if associated with hemodynamic instability (e.g., hypotension) and/or requiring one of the following interventions within 24h*:

    1. Red blood cell transfusion
    2. Volume boluses
    3. Inotropes (either start of inotropes, or increased dose of current therapy)
From onset of severe thrombocytopenia until one week thereafter. The risk of major bleeding or death is predicted within 3 days and within 14 days from each moment of prediction during this time frame.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bronchopulmonary dysplasia (BPD)
Time Frame: 36 weeks of postmenstrual age (PMA)
The number of study participants with BPD defined as dependency on oxygen for at least 28 days and/or the need for respiratory support at 36 weeks of postmenstrual age (PMA).
36 weeks of postmenstrual age (PMA)
Necrotizing enterocolitis (NEC)
Time Frame: Up to 4 weeks after the onset of severe thrombocytopenia
The number of study participants with a new episode of NEC defined as ≥grade IIA as per Bell's criteria
Up to 4 weeks after the onset of severe thrombocytopenia
Proven sepsis
Time Frame: Up to 4 weeks after the onset of severe thrombocytopenia
The number of study participants with a new episode of proven sepsis, including both early-onset (<72 hours after birth) and late-onset (≥72 hours after birth) sepsis, and defined as a positive blood culture treated with antibiotics for 5 or more days or shorter if death occurred while receiving antibiotics. Blood cultures positive for organisms generally considered to be contaminants were only considered sepsis episodes if C-Reactive Protein (CRP) levels were >10 mg/L within 2 days of the blood culture or if there were at least two cultures positive for the organism.
Up to 4 weeks after the onset of severe thrombocytopenia
Retinopathy of prematurity (ROP)
Time Frame: Up to 38 weeks of PMA
The number of study participants with unilateral or bilateral ROP stage ≥2 for which treatment is indicated (e.g., laser or bevacizumab therapy) up to 38 weeks of PMA
Up to 38 weeks of PMA
Mortality
Time Frame: Mortality within 3 days during the first 2 weeks after the onset of severe thrombocytopenia.
Mortality, including if deaths were related to major bleeding (either as a direct result or following withdrawal of life-supporting treatment because of major bleeding). In a sensitivity analysis, the investigators will also assess the composite outcome of major bleeding or mortality.
Mortality within 3 days during the first 2 weeks after the onset of severe thrombocytopenia.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Leiden University Medical Center

Collaborators

Sanquin Research & Blood Bank Divisions
Amsterdam University Medical Center

Investigators

  • Study Director: Hilde van der Staaij, MD, Leiden University Medical Center and Sanquin Blood Supply Foundation
  • Principal Investigator: Suzanne F Fustolo-Gunnink, MD/PhD, Sanquin Blood Supply Foundation
  • Principal Investigator: Enrico Lopriore, MD/PhD/Prof, Leiden University Medical Center
  • Principal Investigator: Johanna G van der Bom, MD/PhD/Prof, Leiden University Medical Center
  • Principal Investigator: Camila Caram-Deelder, MSc/PhD, Leiden University Medical Center
  • Principal Investigator: Karin Fijnvandraat, MD/PhD/Prof, Amsterdam University Medical Center
  • Principal Investigator: Wes Onland, MD/PhD, Amsterdam University Medical Center
  • Principal Investigator: Nan van Geloven, MSc/PhD, Leiden University Medical Center
  • Principal Investigator: Ilaria Prosepe, MSc, Leiden University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 26, 2022

Primary Completion (Actual)

April 30, 2024

Study Completion (Actual)

April 30, 2024

Study Registration Dates

First Submitted

August 17, 2023

First Submitted That Met QC Criteria

September 15, 2023

First Posted (Actual)

September 21, 2023

Study Record Updates

Last Update Posted (Estimated)

September 9, 2025

Last Update Submitted That Met QC Criteria

September 2, 2025

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 22-3028

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Due to the sensitivity of the data, the underlying data sets will not be shared publicly due to ethical/privacy restrictions. However, all analyses will be documented, reproducible and available for audit. The data dictionary will be available upon request or as appendix in the manuscript. We might consider restricted access to the raw data in a repository when the target journal deems this necessary for publication. For future collaboration with the research partners or for data transfer/sharing, written agreements on data management, privacy, data ownership and intellectual properties will be made, such as a research collaboration agreement and data sharing agreement, and discussed with the support of Legal/Privacy/RDM experts where appropriate. In line with the Netherlands Code of Conduct for Research Integrity, raw and processed will be stored for a period of at least 10 years. The LUMC has long-term storage with back-up available for this.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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