PRedicting OutcomeS in Preterm nEonates With thromboCyTopenia (PROSPECT)

Completed

• Conditions: Neonatal Thrombocytopenia; Intraventricular Hemorrhage; Platelet Transfusion
• Interventions: Drug: Platelets

• Registration Number: NCT06043050
• Lead Sponsor: Leiden University Medical Center

Brief Summary

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 retrospective 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.

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 retrospective 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 Timeline

• Study Start: 2022-09-26
• Study First Submitted: 2023-08-17
• Study First Submitted QC: 2023-09-15
• Study First Posted: 2023-09-21
• Primary Completion: 2024-04-30
• Study Completion: 2024-04-30
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-01
• Last Update Posted: 2024-08-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1042

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Neonates with severe thrombocytopenia	Platelets	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.

Primary Outcome Measures

Name	Time	Method
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.	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)

Trial Locations

Locations (12)

University Medical Center Groningen, Beatrix Children's hospital; 🇳🇱 Groningen, Netherlands

Isala clinics; 🇳🇱 Zwolle, Overijssel, Netherlands

Erasmus University Medical Center, Sophia pediatric hospital; 🇳🇱 Rotterdam, South Holland, Netherlands

Leiden University Medical Center, Willem Alexander Children's hospital; 🇳🇱 Leiden, South Holland, Netherlands

Máxima Medical Center; 🇳🇱 Veldhoven, Brabant, Netherlands

Radboud University Medical Center, Amalia Children's hospital; 🇳🇱 Nijmegen, Gelderland, Netherlands

Maastricht University Medical Center, MosaKids; 🇳🇱 Maastricht, Limburg, Netherlands

Amsterdam University Medical Center, Emma Children's hospital, location VUmc; 🇳🇱 Amsterdam, North Holland, Netherlands

Amsterdam University Medical Center, Emma Children's hospital, location AMC; 🇳🇱 Amsterdam, North Holland, Netherlands

University Medical Center Utrecht, Wilhelmina Children's hospital; 🇳🇱 Utrecht, Netherlands

Karolinska University Hospital; 🇸🇪 Stockholm, Södermanland And Uppland, Sweden

Charité - Universitätsmedizin Berlin; 🇩🇪 Berlin, Metropolregion Berlin-Brandenburg, Germany