PRedicting OutcomeS in Preterm nEonates With thromboCyTopenia

NCT06043050 | Completed

• 1 other identifier: 22-3028
• Study Type: observational
• Target: 1,042
• Locations: 3 countries
• Sites: 12

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 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.

Conditions

Neonatal Thrombocytopenia; Intraventricular Hemorrhage; Platelet Transfusion

Keywords

Sequential prediction under interventions; Causal prediction; Hemorrhage; Neonate; Thrombocytopenia

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

Study Arms (1)

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

Interventions

Platelets DRUG

Observational data: all platelet transfusions recorded in routine care medical file data.

Also known as: Platelet transfusion

Neonates with severe thrombocytopenia

Eligibility Criteria

• Age: 22 Weeks - 34 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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.

You may qualify if:

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

You may not qualify if:

• A severe congenital malformation;
• 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);
• Only platelet counts \<50x109/L in the context of exchange transfusion;
• 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.

Sponsors & Collaborators

• Leiden University Medical Center: lead
• Sanquin Research & Blood Bank Divisions: collaborator
• Amsterdam University Medical Center: collaborator

Study Sites (12)

Charité - Universitätsmedizin Berlin

Berlin, Metropolregion Berlin-Brandenburg, 10117, Germany

Location

Radboud University Medical Center, Amalia Children's hospital

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Maastricht University Medical Center, MosaKids

Maastricht, Limburg, 6229 HX, Netherlands

Location

Máxima Medical Center

Veldhoven, North Brabant, 5504 DB, Netherlands

Location

Amsterdam University Medical Center, Emma Children's hospital, location VUmc

Amsterdam, North Holland, 1081 HV, Netherlands

Location

Amsterdam University Medical Center, Emma Children's hospital, location AMC

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

Isala clinics

Zwolle, Overijssel, 8025 AB, Netherlands

Location

University Medical Center Groningen, Beatrix Children's hospital

Groningen, Provincie Groningen, 9713 GZ, Netherlands

Location

Leiden University Medical Center, Willem Alexander Children's hospital

Leiden, South Holland, 2333 ZA, Netherlands

Location

Erasmus University Medical Center, Sophia pediatric hospital

Rotterdam, South Holland, 3015 CN, Netherlands

Location

University Medical Center Utrecht, Wilhelmina Children's hospital

Utrecht, Utrecht, 3584 EA, Netherlands

Location

Karolinska University Hospital

Stockholm, Södermanland and Uppland, 171 76, Sweden

Location

Related Publications (9)

• Curley A, Stanworth SJ, Willoughby K, Fustolo-Gunnink SF, Venkatesh V, Hudson C, Deary A, Hodge R, Hopkins V, Lopez Santamaria B, Mora A, Llewelyn C, D'Amore A, Khan R, Onland W, Lopriore E, Fijnvandraat K, New H, Clarke P, Watts T; PlaNeT2 MATISSE Collaborators. Randomized Trial of Platelet-Transfusion Thresholds in Neonates. N Engl J Med. 2019 Jan 17;380(3):242-251. doi: 10.1056/NEJMoa1807320. Epub 2018 Nov 2.

  PMID: 30387697 BACKGROUND

• Davenport P, Sola-Visner M. Hemostatic Challenges in Neonates. Front Pediatr. 2021 Mar 2;9:627715. doi: 10.3389/fped.2021.627715. eCollection 2021.

  PMID: 33738269 BACKGROUND

• Davenport PE, Wood TR, Heagerty PJ, Sola-Visner MC, Juul SE, Patel RM. Platelet Transfusion and Death or Neurodevelopmental Impairment in Children Born Extremely Preterm. JAMA Netw Open. 2024 Jan 2;7(1):e2352394. doi: 10.1001/jamanetworkopen.2023.52394.

  PMID: 38261320 BACKGROUND

• Fustolo-Gunnink SF, Fijnvandraat K, van Klaveren D, Stanworth SJ, Curley A, Onland W, Steyerberg EW, de Kort E, d'Haens EJ, Hulzebos CV, Huisman EJ, de Boode WP, Lopriore E, van der Bom JG; PlaNeT2 and MATISSE collaborators. Preterm neonates benefit from low prophylactic platelet transfusion threshold despite varying risk of bleeding or death. Blood. 2019 Dec 26;134(26):2354-2360. doi: 10.1182/blood.2019000899.

  PMID: 31697817 BACKGROUND

• Fustolo-Gunnink SF, Fijnvandraat K, Putter H, Ree IM, Caram-Deelder C, Andriessen P, d'Haens EJ, Hulzebos CV, Onland W, Kroon AA, Vijlbrief DC, Lopriore E, van der Bom JG. Dynamic prediction of bleeding risk in thrombocytopenic preterm neonates. Haematologica. 2019 Nov;104(11):2300-2306. doi: 10.3324/haematol.2018.208595. Epub 2019 Feb 28.

  PMID: 30819913 BACKGROUND

• Hernan MA, Wang W, Leaf DE. Target Trial Emulation: A Framework for Causal Inference From Observational Data. JAMA. 2022 Dec 27;328(24):2446-2447. doi: 10.1001/jama.2022.21383.

  PMID: 36508210 BACKGROUND

• Keogh RH, Van Geloven N. Prediction Under Interventions: Evaluation of Counterfactual Performance Using Longitudinal Observational Data. Epidemiology. 2024 May 1;35(3):329-339. doi: 10.1097/EDE.0000000000001713. Epub 2024 Apr 18.

  PMID: 38630508 BACKGROUND

• van der Staaij H, Stanworth SJ, Fustolo-Gunnink SF. Prophylactic Platelet Transfusions: Why Less Is More. Clin Perinatol. 2023 Dec;50(4):775-792. doi: 10.1016/j.clp.2023.07.007. Epub 2023 Aug 31.

  PMID: 37866847 BACKGROUND

• van Geloven N, Swanson SA, Ramspek CL, Luijken K, van Diepen M, Morris TP, Groenwold RHH, van Houwelingen HC, Putter H, le Cessie S. Prediction meets causal inference: the role of treatment in clinical prediction models. Eur J Epidemiol. 2020 Jul;35(7):619-630. doi: 10.1007/s10654-020-00636-1. Epub 2020 May 22.

  PMID: 32445007 BACKGROUND

MeSH Terms

Conditions

Thrombocytopenia, Neonatal Alloimmune; Hemorrhage; Thrombocytopenia

Interventions

Platelet Count; Platelet Transfusion

Condition Hierarchy (Ancestors)

Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Blood Cell Count; Cell Count; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Hematologic Tests; Platelet Function Tests; Investigative Techniques; Cell Physiological Phenomena; Blood Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Blood Component Transfusion; Blood Transfusion; Biological Therapy; Therapeutics

Study Officials

• Hilde van der Staaij, MD

  Leiden University Medical Center and Sanquin Blood Supply Foundation

  STUDY DIRECTOR

• 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

• Enrico Lopriore, MD/PhD/Prof

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

• Karin Fijnvandraat, MD/PhD/Prof

  Amsterdam University Medical Center

  PRINCIPAL INVESTIGATOR

• Suzanne F Fustolo-Gunnink, MD/PhD

  Sanquin Blood Supply Foundation

  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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Coordinating Investigator

Study Record Dates

• First Submitted: August 17, 2023
• First Posted: September 21, 2023
• Study Start: September 26, 2022
• Primary Completion: April 30, 2024
• Study Completion: April 30, 2024
• Last Updated: September 9, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (10); SE (1); DE (1)