Oxygen Therapy and Pregnancy in Sickle Cell Disease

Sickle Cell Disease Clinical Trial

— DRO2G  

Official title:

Impact of Home-based Oxygen Therapy on Maternal and Fetal Complications, in Pregnant Women With Sickle Cell Disease. A Randomized Multi-center Trial.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02813850
• Other study ID #: P140030
• Secondary ID: 2015-A01276-43
• Status: Completed
• Phase: Phase 3
• Start date: October 5, 2016
• Est. completion date: August 12, 2022

Study information

• Verified date: November 2022
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 178
• Est. completion date: August 12, 2022
• Est. primary completion date: December 3, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Pregnant women from 18 to 50 years old
• Maximal term: 20SA
• Patient with sickle cell disease
• Consent form signed by the patient
• Affiliated or beneficiary of a health insurance regimen and State Medical Aid.

Exclusion Criteria:

• Patients with transfusion restrictions
• Patients whose house can not receive the device
• Patients who have a weekly use of prophylactic oxygen therapy at home
• Patients who don't understand the operating instructions *Include patients with a doctor's prescription only. The portable oxygen concentrator will be removed from patients' home at the initiation visit prior to the overnight home oximetry test.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Device:
• oxygen therapy
Oxygen therapy early in the night (2L/min) during 4hours per days

Locations

Country	Name	City	State
France	Hôpital Necker Enfants-Malades (Public Hospitals of Paris)	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of at least one vaso-occlusive complication which last more than 24h	Painful vaso-occlusive episodes in bones, acute chest syndrome, ischemic stroke, cardiomyopathy, pulmonary hypertension, splenic and hepatic sequestration, death of the mother	30 days postpartum
Secondary	Occurrence of at least one vaso-occlusive complication which last more than 24h	Painful vaso-occlusive episodes in bones, acute chest syndrome, ischemic stroke, cardiomyopathy, pulmonary hypertension, splenic and hepatic sequestration, death of the mother	30 days postpartum
Secondary	Occurrence of pregnancy-induced hypertension, pre-eclampsia, eclampsia		20 months
Secondary	Occurence of hospitalisation because of premature delivery risk		20 months
Secondary	Occurence of late miscarriage		20 months
Secondary	Occurence of Preterm (<35SA) and very preterm ( from 26 to 32SA)		20 months
Secondary	Type of delivery (vaginal, active, caesarean)		20 months
Secondary	Number of days hospitalisation postpartum		20 months
Secondary	Occurence of Neonatal complications ( respiratory distress, analgesics withdrawal symptom)		20 months
Secondary	Number of days of hospitalisation for the newborn		20 months
Secondary	Number of days of hospitalisation in resuscitation unit for the newborn		20 months
Secondary	Newborn weight		20 months
Secondary	Newborn size		20 months
Secondary	Newborn head circumference		20 months
Secondary	Apgar score assess 1 min after birth		20 months
Secondary	Apgar score assess 5 min after birth		20 months
Secondary	Apgar score assess 10 min after birth		20 months
Secondary	Perinatal and neonatal death		20 months
Secondary	pH of of the newborn		20 months
Secondary	Lactate of of the newborn		20 months
Secondary	Number of days using painkiller (level II and III) during pregnancy		20 months
Secondary	Number of urgent consultation		20 months
Secondary	Number of days of hospitalisation and hospitalisation in intensive care during pregnancy		20 months
Secondary	Stage of pregnancy at the first transfusion		20 months
Secondary	Total volume of transfusion during pregnancy		20 months
Secondary	Way of transfusion: simple, bleeding-transfusion, erythrocytapheresis		20 months
Secondary	Maternal, fetal and newborn tolerability of home-based oxygen therapy during pregnancy		20 months