Oxygen Therapy and Pregnancy in Sickle Cell Disease
Condition: Sickle Cell Disease
MeSH terms: Anemia, Sickle Cell
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to assess the efficiency of the preventive oxygen therapy on the
      occurrence of vaso-occlusive complications, which last more than 24 hours and require
      hospitalisation, in women with sickle cell disease.
    

Detailed description: 
      Sickle cell disease (SCD) corresponds to a group of inherited disorders with clinical
      manifestations resulting from the biochemical consequences of a single-base substitution of
      valine by glutamic acid at position 6 of the ß-hemoglobin (Hb) subunit (HbA [ß6val] to HbS
      [ß6glu]). When the oxygen tension is low, the solubility of HbS falls and the molecules
      polymerize. In turn, the intracellular formation of HbS polymers results in red blood cell
      (RBC) sickling. The aggregation of sickle cells is responsible for the vaso-occlusive crises
      (VOCs) that characterize SCD.

      Thanks to improvements in the management of SCD patients, over 95% of affected infants
      survive to adulthood. Pregnancy is a high-risk situation for women with sickle cell disease,
      especially in the third trimester, during delivery and in the post-partum period. Conversely
      sickle cell disease can lead to pregnancy complications for both mother and fetus since
      maternal-fetal mortality remains elevated.

      RBC transfusions and careful prevention of infections represent the only available treatments
      in this situation.

      The complexity of this setting and the associated therapeutic strategy is further accentuated
      by the high frequency of post-transfusion side effects during SCD pregnancies, can indirectly
      affect the newborn by inducing hypoxia, and may ultimately prevent the woman from receiving
      further transfusions (RCOG, 2015) (Tuck et al, 1983). Post-transfusion complications
      constitute negative prognostic factors that affect both the mother's health and fetal
      development and thus increase the risk of premature death.

      Another factor complicating the outcome of the pregnancy is the increase in oxygen demand in
      order to satisfy the increased metabolic requirements of the placenta and fetus. As the
      maternal oxygen reserve can be compromised during pregnancy for several reasons (such as the
      increased oxygen consumption, the SCD related anemia accentuated by the plasmatic increase),
      patients are particularly susceptible to hypoxemia - leading to the exacerbation of sickling
      events and SCD-related complications. (Hill & Pickinpaugh, 2008)(Thame et al, 2007)(Rathod et
      al, 2007a)(Cines et al, 1998)(Hassell, 2005)(Pantanowitz et al, 2000)(Rathod et al, 2007b)
      Moving from this observation, the first innovative approach introduced was the widespread use
      of prophylactic oxygen treatment at home. The rationale behind this change came from
      experiments on a murine model of SCD mice, in which a high-oxygen environment during
      pregnancy was associated with a lower prenatal fetal/maternal mortality rate (Ye et al,
      2008). The absence of severe complications was also noticed in some women who could not be
      transfused (because of severe alloimmunization) and who were already receiving oxygen therapy
      at home before pregnancy.

      Then a preliminary retrospective study was performed to evaluate the clinical benefit of the
      widespread use of prophylactic oxygen treatment at home. It indicates that this innovative
      treatment is safe and seems to be associated with a significant decrease in the transfusion
      rate in SCD patients during pregnancy.

      These findings are encouraging, but they are preliminary and bias have to be taken into
      account. These results have to be confirmed by a randomized trial.

      The project aim is to assess preventive oxygen therapy impact on women with sickle cell
      disease, their fetal and their newborn. Firstly, investigators want to assess preventive
      home-based oxygen therapy efficacy for preventing vaso-occlusive complications which last 24
      hours and require a hospitalization. Secondly, they want to assess oxygen therapy impact on
      prevention and characteristics of obstetrical complications, prevention of neonatal
      complications, fetal and newborn's characteristics, type of medical care, transfusion balance
      sheet, way of transfusion and maternal, fetal and newborn tolerability of home-based oxygen
      therapy during pregnancy.

      For this they propose to analyze 200 pregnant SCD women. 100 women in the first arm with
      standard medical care. 100 women in the second arm who will have home-based oxygen therapy
      early at night.

      This study will be performed in 9 French hospitals. Blood samples of SCD women and blood cord
      will be drawn to monitor red cell adherence protein expression and function and their
      mechanic and adhesive properties.
    

Intervention name(s): oxygen therapy
Intervention type(s): Device
Intervention description(s): Oxygen therapy early in the night (2L/min) during 4hours per days
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: sickle cell disease; oxygen therapy; pregnancy; pregnancy in sickle cell disease