Infant, Extremely Low Birth Weight, Infant, Newborn, Diseases, Infant, Small for Gestational Age, Neonatal, Platelet Transfusion, Thrombocytopenia, Thrombosis
Conditions
Keywords
platelet transfusion, neonatal, thrombosis
Brief summary
The objective of the NeoPlaTT trial is to test whether, among extremely preterm infants born at 23 0/7 to 26 6/7 weeks' gestation, a lower platelet transfusion threshold, compared to a higher threshold, improves survival without major or severe bleeding up to 40 0/7 weeks' postmenstrual age (PMA).
Detailed description
Thrombocytopenia, defined as a platelet count \<150 x 10\^9/L, is a common neonatal problem that affects 22% to 35% of infants admitted to the neonatal intensive care unit. Platelets are important for primary hemostasis to prevent blood extravasation after vascular injury. Based on the role of platelets in hemostasis, prophylactic platelet transfusions are routinely administered to preterm infants with thrombocytopenia to prevent bleeding. The incidence of thrombocytopenia and administration of platelet transfusion are both inversely related to the gestational age at birth. Currently, there is uncertainty regarding the optimal platelet transfusion threshold, particularly among the most immature infants in the first week of life, which represents the period of highest bleeding risk. The NeoPlaTT trial was designed to address this pressing uncertainty in the highest risk population (\<27 weeks GA). It will test whether a threshold of 20x10\^9/L could be safely used after the first week of life, when the risk of serious bleeding is significantly lower, and reduce the need for platelet transfusion altogether. The results of this study have a potential to change clinical practice and improve outcomes in this vulnerable population, while also decreasing costs and resource utilization. This is a randomized trial with 1:1 allocation to parallel arms. Infants, inborn or outborn, who are admitted to participating NICUs, and who meet the inclusion and exclusion criteria, will be invited to enroll into the trial for platelet count monitoring. Only consented and enrolled infants meeting the additional platelet count trigger of \< 50 x 10\^9/L (postnatal days 1-7) or \<35 x 10\^9/L (8 or more postnatal days) will be randomized. Postnatal day 1 starts at birth. Randomization will be allowed to occur up to 36 6/7 weeks' PMA; subjects will be monitored through 40 0/7 weeks PMA. Approximately 30% of consented and enrolled infants are expected to meet the platelet count threshold for randomization.
Interventions
PROCEDUREHigher Platelet Transfusion Threshold
Infants randomized to this arm will be monitored for a platelet transfusion threshold of 50 x 10\^9/L during postnatal days 1-7, and then for a platelet transfusion threshold of 35 x 10\^9/L at 8 or more postnatal days of life. Infants will remain on this protocol-driven threshold through 40 0/7 weeks postmenstrual age. The platelet dose will be 10 ml/kg administered over 60-120 minutes.
PROCEDURELower Platelet Transfusion Threshold
Infants randomized to this arm will be monitored for a platelet transfusion threshold of 25 x 10\^9/L during postnatal days 1-7, and then for a platelet transfusion threshold of 20 x 10\^9/L at 8 or more postnatal days of life. Infants will remain on this protocol-driven threshold through 40 0/7 weeks postmenstrual age. The platelet dose will be 10 ml/kg administered over 60-120 minutes.
Sponsors
NICHD Neonatal Research Network
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
There will be no blinding/masking of the treatment group allocation to providers or parents to ensure providers are aware of treatment allocation to guide platelet transfusions. This is necessary to ensure adherence to the treatment arms. However, a standard tool will be used to assess bleeding as described below and grading of the severity of bleeding will be performed centrally. In addition, radiologists interpreting cranial ultrasound findings will be blinded to treatment arm allocation.
Intervention model description
Randomized trial with 1:1 allocation to parallel arms within strata of Study Center and gestational age (23-24 weeks and 25-26 weeks PMA). Multiples will be randomized independently. Approximately 30% of enrolled participants are expected to meet the platelet count threshold for randomization. The target sample size for randomization is 730, or 365 per arm.
Eligibility
Sex/Gender
ALL
Age
1 Years to 48 Years
Healthy volunteers
Yes
Inclusion criteria
* Gestational age of 23 0/7 to 26 6/7 weeks * Postnatal age of \< 48 hours
Exclusion criteria
* Comfort care or withdrawal of care planned * Neonatal alloimmune thrombocytopenia or suspected/confirmed congenital platelet or bleeding disorder * Receipt of platelet transfusion * No receipt of Vitamin K * Parents/guardian decline consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival without major or severe bleeding | Randomization to 40 0/7 weeks postmenstrual age, death, discharge, or transfer outside of the Study Center, whichever occurs first (an average of 98 days postnatal age) | Bleeding will be assessed using the neonatal Bleeding Assessment Tool (NeoBAT), a validated bleeding assessment tool (Venkatesh V, 2013) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Death | Randomization to 52 0/7 weeks' postmenstrual age, death, discharge, or transfer outside of the Study Center, whichever occurs first, per Neonatal Research Network Generic Research Database Registry protocol. | — |
| Major or severe bleeding | Randomization to 40 0/7 weeks postmenstrual age, death, discharge, or transfer outside of the Study Center, whichever occurs first (an average of 98 days postnatal age) | Bleeding will be assessed using the neonatal Bleeding Assessment Tool (NeoBAT), a validated bleeding assessment tool (Venkatesh V, 2013) |
| Number of platelet transfusions | Randomization to 40 0/7 weeks postmenstrual age, death, discharge, or transfer outside of the Study Center, whichever occurs first (an average of 98 days postnatal age) | — |
| At least one platelet transfusion | Randomization to 40 0/7 weeks postmenstrual age, death, discharge, or transfer outside of the Study Center, whichever occurs first (an average of 98 days postnatal age) | — |
| Bronchopulmonary dysplasia among survivors to 36 weeks postmenstrual age | At 36 weeks postmenstrual age | — |
| Retinopathy of Prematurity (ROP) | Randomization to 52 0/7 weeks' postmenstrual age, death, discharge, or transfer outside of the Study Center, whichever occurs first, per Neonatal Research Network Generic Research Database Registry protocol. | Stage 3 ROP, or stage 1 or 2 in Zone 1, or plus disease |
| Periventricular leukomalacia | Randomization to 52 0/7 weeks' postmenstrual age, death, discharge, or transfer outside of the Study Center, whichever occurs first, per Neonatal Research Network Generic Research Database Registry protocol. | — |
Countries
United States
Contacts
CONTACTRavi M Patel, MD
CONTACTAbhik Das, PhD
PRINCIPAL_INVESTIGATORRavi M Patel, MD
Emory University
Outcome results
None listed