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Oxygen Therapy and Pregnancy in Sickle Cell Disease (DRO2G)

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ClinicalTrials.gov Identifier: NCT02813850
Recruitment Status : Recruiting
First Posted : June 27, 2016
Last Update Posted : March 20, 2020
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date  ICMJE June 23, 2016
First Posted Date  ICMJE June 27, 2016
Last Update Posted Date March 20, 2020
Actual Study Start Date  ICMJE October 5, 2016
Estimated Primary Completion Date November 5, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 18, 2020)
Occurrence of at least one vaso-occlusive complication which last more than 24h [ Time Frame: 30 days postpartum ]
Painful vaso-occlusive episodes in bones, acute chest syndrome, ischemic stroke, cardiomyopathy, pulmonary hypertension, splenic and hepatic sequestration, death of the mother
Original Primary Outcome Measures  ICMJE
 (submitted: June 23, 2016)
Occurrence of at least one vaso-occlusive complication which last more than 24h [ Time Frame: During pregnancy ]
Painful vaso-occlusive episodes in bones, acute chest syndrome, ischemic stroke, cardiomyopathy, pulmonary hypertension, splenic and hepatic sequestration, death of the mother
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 23, 2016)
  • Occurrence of at least one vaso-occlusive complication which last more than 24h [ Time Frame: 30 days postpartum ]
    Painful vaso-occlusive episodes in bones, acute chest syndrome, ischemic stroke, cardiomyopathy, pulmonary hypertension, splenic and hepatic sequestration, death of the mother
  • Occurrence of pregnancy-induced hypertension, pre-eclampsia, eclampsia [ Time Frame: 20 months ]
  • Occurence of hospitalisation because of premature delivery risk [ Time Frame: 20 months ]
  • Occurence of late miscarriage [ Time Frame: 20 months ]
  • Occurence of Preterm (<35SA) and very preterm ( from 26 to 32SA) [ Time Frame: 20 months ]
  • Type of delivery (vaginal, active, caesarean) [ Time Frame: 20 months ]
  • Number of days hospitalisation postpartum [ Time Frame: 20 months ]
  • Occurence of Neonatal complications ( respiratory distress, analgesics withdrawal symptom) [ Time Frame: 20 months ]
  • Number of days of hospitalisation for the newborn [ Time Frame: 20 months ]
  • Number of days of hospitalisation in resuscitation unit for the newborn [ Time Frame: 20 months ]
  • Newborn weight [ Time Frame: 20 months ]
  • Newborn size [ Time Frame: 20 months ]
  • Newborn head circumference [ Time Frame: 20 months ]
  • Apgar score assess 1 min after birth [ Time Frame: 20 months ]
  • Apgar score assess 5 min after birth [ Time Frame: 20 months ]
  • Apgar score assess 10 min after birth [ Time Frame: 20 months ]
  • Perinatal and neonatal death [ Time Frame: 20 months ]
  • pH of of the newborn [ Time Frame: 20 months ]
  • Lactate of of the newborn [ Time Frame: 20 months ]
  • Number of days using painkiller (level II and III) during pregnancy [ Time Frame: 20 months ]
  • Number of urgent consultation [ Time Frame: 20 months ]
  • Number of days of hospitalisation and hospitalisation in intensive care during pregnancy [ Time Frame: 20 months ]
  • Stage of pregnancy at the first transfusion [ Time Frame: 20 months ]
  • Total volume of transfusion during pregnancy [ Time Frame: 20 months ]
  • Way of transfusion: simple, bleeding-transfusion, erythrocytapheresis [ Time Frame: 20 months ]
  • Maternal, fetal and newborn tolerability of home-based oxygen therapy during pregnancy [ Time Frame: 20 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Oxygen Therapy and Pregnancy in Sickle Cell Disease
Official Title  ICMJE Impact of Home-based Oxygen Therapy on Maternal and Fetal Complications, in Pregnant Women With Sickle Cell Disease. A Randomized Multi-center Trial.
Brief 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Sickle Cell Disease
Intervention  ICMJE Device: oxygen therapy
Oxygen therapy early in the night (2L/min) during 4hours per days
Study Arms  ICMJE
  • No Intervention: control
    standard medical care
  • Experimental: oxygen therapy
    Intervention: Device: oxygen therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 23, 2016)
200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 5, 2022
Estimated Primary Completion Date November 5, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Laure JOSEPH, MD, PhD 00 33 1 44 49 52 74
Contact: Valérie JOLAINE, Master +33 1 42 19 28 79 valerie.jolaine@aphp.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02813850
Other Study ID Numbers  ICMJE P140030
2015-A01276-43 ( Registry Identifier: ID RCB )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Alexandra BENACHI, MD, PhD Assistance Publique - Hôpitaux de Paris
Principal Investigator: Laure JOSEPH, MD,PhD Assistance Publique - Hôpitaux de Paris
Principal Investigator: Marina CAVAZZANA, MD, PhD Assistance Publique - Hôpitaux de Paris
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP