To assess whether a higher prophylactic platelet transfusion threshold is superior to the lower thresholds in reducing the proportion of patients who experience a major bleed or death up to study day 28.
ID
Source
Brief title
Condition
- Platelet disorders
- Congenital and peripartum neurological conditions
- Neonatal and perinatal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The proportion of patients who either die or experience a major bleed up to and
including study day 28.
Secondary outcome
• Proportion of patients surviving to go home following a major bleed
• Proportion of patients surviving to go home without having had a major bleed
• Proportion of patients who have died up to study day 28
• Proportion of patients who sustain a major bleed up to study day 28
• The rate and time from randomization of minor, moderate and major bleeding
derived from the bleeding assessment tool up to study day 14, and for major
bleeds up to study day 28.
• Number of platelet units transfused up to study day 28
• Time to discharge home
• Neuro-developmental outcome as assessed by the Bayley III scale of infant
development or a Dutch self-completion questionnaire (PARCA-R: Parent Report of
Children*s Abilities for very Premature Infants) and a supplementary
questionnaire designed specifically for MATISSE. This assessment will take
place at 2 year corrected postnatal age.
• Platelet transfusion-related adverse events up to discharge
Background summary
Preterm neonates with thrombocytopenia are often treated with prophylactic
thrombocyte transfusions, with the aim of preventing major bleeding. Practice
in many Dutch neonatal units has seen the adoption of thresholds for
prophylactic platelet transfusions at around 25-50 x10^9/L. However, the
effectiveness and safety of any thresholds in preterm neonates has not been
established in randomised controlled trials. Several observational trials show
that more restrictive guidelines do not cause increased bleeding risk.
Study objective
To assess whether a higher prophylactic platelet transfusion threshold is
superior to the lower thresholds in reducing the proportion of patients who
experience a major bleed or death up to study day 28.
Study design
MATISSE is a randomized, parallel group, superiority trial. Preterm neonates
with severe thrombocytopenia are randomized between a high transfusion
threshold (50x10^9/L) and a low transfusion threshold arm (25x10^9/L). Regular
observational bleeding scores and cranial ultrasounds will be performed to
assess the presence of bleeding. Follow up continues until a gestational age of
38 weeks or discharge. A follow-up visit to assess neurologic development at 2
years corrected age will also be performed.
Intervention
Randomization between a thrombocyte transfusion threshold of 50x10^9/L and a
thrombocyte transfusion threshold of 25x10^9/L.
Study burden and risks
Daily bleeding scores are based on standard observations and do not require
extra manipulation of the neonates. Cranial ultrasounds are known to be safe
and will be combined with standard ultrasound regimes where possible. No extra
blood draws will be performed for this study. The two year neurodevelopmental
follow up visit is standard care for the majority of preterm neonates, but will
be scheduled on top of standard care for a small subset. Risk of an excess of
severe bleeding events in either arm of the trial will be addressed by close
monitoring of all neonates using the pre-piloted bleeding assessment tool by
trained clinical staff, education to highlight bleeding events and severity,
and immediate reporting of all major bleeding events. In addition, the PlaNet-2
trial has already performed an interim analysis and the Independent Data
Monitoring Committee (IDMC) is closely monitoring the primary outcome
(mortality and major bleeds) as well as safety data for any imbalance between
the two arms. It is possible that neonates will benefit from receiving either
more of fewer transfusions. Because of the current lack of evidence, it is
impossible to predict whether this will be the case. We do not expect neonates
to be harmed by this study, based on observational studies suggesting that
lowering the transfusion threshold does not increase the number of major
bleeds. This study has to be conducted in this study population because preterm
neonates are a very distinct population with organ systems (including the
hemostatic system) that are still immature and high risk of specific
age-related diseases such as necrotizing enterocolitis (NEC) and other
diseases. Results from adult or pediatric studies can therefore not be
extrapolated to this population.
North Bristol Park, Northway 500
Bristol BS34 7QH
GB
North Bristol Park, Northway 500
Bristol BS34 7QH
GB
Listed location countries
Age
Inclusion criteria
1. Written informed consent obtained
2. Admission to a participating NICU (includes postnatal transfer)
3. <34 weeks gestational age at birth
4. A platelet count of <50 x10^9/L
5. Cranial ultrasound scan must have been undertaken less than 6 hours prior to randomisation in order to rule out recent major intraventricular hemorrhage
Exclusion criteria
1. Major/life-threatening congenital malformations (e.g. chromosomal anomalies, Fanconi*s anaemia, Thrombocytopenia Absent Radius syndrome (TAR));
2. The occurrence of a major/ severe bleed within the previous 72 hours. However, the neonate may be eligible for randomisation later, once 72 hours has elapsed, provided there are no further major bleeds and the baby meets all the inclusion criteria;
3. All foetal intracranial haemorrhages excluding subependymal haemorrhage from any antenatal ultrasound scan;
4. Known immune thrombocytopenia or family history of alloimmune thrombocytopenia or maternal antiplatelet antibodies or maternal idiopathic thrombocytopenic purpura;
5. Neonates judged by the attending neonatologist to be unlikely to survive more than a few hours at the time of proposed randomisation;
6. Neonates who were not given parenteral Vitamin K after birth.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | De MATISSE centra staan als Nederlandse includerende centra genoemd bij de registratie van de Engelse Planet-2 studie. |
| CCMO | NL45931.018.13 |