AimTo determine whether the prophylactic use of IVIg reduces the need for ET in neonates with Rh-D hemolytic disease.
ID
Source
Brief title
Condition
- Haemolyses and related conditions
- Blood and lymphatic system disorders congenital
- Neonatal and perinatal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
13.1 Primary outcomes
a. Use of ET (%; proportion of children receiving one or more ET)
b. Number of ET performed per infant
Secondary outcome
13.2 Secondary outcomes
c. Duration of phototherapy (number of days)
d. Maximum serum bilirubin (mmol/l)
e. Change in bilirubin in first 24 hours (%)
f. Change in bilirubin in first 48 hours (%)
g. Use of top-up red cell transfusion in first week of life (%; proportion of
children receiving one or more red cell transfusion and number of transfusions
per infant)
h. Use of simple red cell transfusion after first week and until 3 months of
life (%; proportion of children receiving one or more red cell transfusion and
number of transfusions per infant)
i. Duration of hospital stay (number of days)
Background summary
Background
Rh-D disease of the neonate may lead to excessive hyperbilirubinemia and
permanent brain damage (i.e. kernicterus). Traditional neonatal treatment of
Rh-D disease consists of intensive phototherapy and ET. Phototherapy lowers
bilirubin through photo-oxidation, whereas ET removes bilirubin and hemolytic
antibodies, and corrects anemia. ET is a high-risk invasive procedure
associated with a significant rate of adverse effects. Although the mortality
rate associated with ET is nowadays reported to be less than 0.3% in the term
infants, the morbidity rate associated with ET is at least 5%.
Neonatal treatment with IVIg has been suggested as an alternative therapy for
ET in hemolytic disease of the neonate (HDN). A few small randomized controlled
trials (RCT) have suggested that IVIG combined with phototherapy reduces the
serum bilirubin and the need for ET in neonates with HDN compared with
phototherapy alone6-9. In these studies, treatment with IVIg also reduced the
duration of phototherapy and length of hospitalization, but increased the need
for late red cell transfusions7. However, the number of patients included in
these RCTs was small and the study- design and inclusion criteria varied
considerably. In one study, infants with ABO incompatibility were also
included. Moreover, an unexpected and large number of these children with ABO
incompatibility and HDN required ET8. Finally, the criteria for exchange
transfusion were discordant between the various studies.
Therefore, the evidence thus far is considered insufficient to recommend the
routine use of IVIg10. A recent Cochrane review suggested that the results of
further trials of higher quality should be awaited10. In contrast, the American
Association of Pediatrics (AAP) recommended in 2004 the use of IVIg (0.5 - 1
g/kg) in HDN in case of failure of phototherapy, despite the limited data1.
Given the conflicting recommendations, a well-designed randomized controlled
trial (RCT) for the use of IVIg in HDN is urgently needed.
Study objective
Aim
To determine whether the prophylactic use of IVIg reduces the need for ET in
neonates with Rh-D hemolytic disease.
Study design
Prospective randomized double blind placebo controlled trial
Intervention
Prior to randomization, stratification into two groups (with and without
intrauterine blood transfusion) will occur. At birth, patients are then
randomized to the IVIg treatment group (group A) or placebo control group
(group B) by opening a sealed envelop containing a study number. In group A,
patients will receive conventional intensive phototherapy plus prophylactic
IVIg as a single dose of 0.75 g/kg within the first 4 hours after birth. In
group B, patients will receive conventional intensive phototherapy plus an
equal amount of glucose 5% intravenous infusion (placebo) on day one. For
details on the phototherapy protocol, see paragraph 18.
Study burden and risks
Apart from the excellent safety profile for transmission of viral disease, all
blood products (incl IVIg) have a theoretical risk for transmission of variant
Creutzfeldt-Jakob disease. At present, this risk is considered extremely low.
albinusdreef 2
2300 rc Leiden
Nederland
albinusdreef 2
2300 rc Leiden
Nederland
Listed location countries
Age
Inclusion criteria
7.1 Inclusion criteria: Neonates of 35 or more weeks of gestation with Rh-D hemolytic disease admitted to the neonatal nursery of the Leiden University Medical Center (LUMC). Rh-D hemolytic disease was defined as (1) Antibody Dependent Cellular Cytotoxicity-test (ADCC) > 50% and (2) positive direct Coombs test in a Rh-D positive fetus/neonate with a Rh-D negative mother and a Rh-D positive father. Previous intra-uterine transfusions and the presence of additional antibodies besides anti-D are not reasons for exclusion.
Exclusion criteria
7.2 Exclusion criteria: (1) Perinatal asphyxia (defined as an Apgar score at 5 minutes less than 3 and/or umbilical cord arterial pH less than 7.0). (2) Neonates with hemolytic disease other than Rh-D. (3) Neonates with Rh-D hemolytic disease presenting > 24 hours after birth.
Design
Recruitment
metc-ldd@lumc.nl
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 |
|---|---|
| CCMO | NL11345.058.06 |