Treatment of Anaemia After Caesarean With Intravenous Versus Oral Iron and Postpartum Depression: a Multicentric Randomized Open-labelled Controlled Trial
Trial Snapshot
- Phase
- Phase 4
- Status
- Recruiting
- Enrollment
- 2,860
- Locations
- 1
- Primary Endpoint
- Prevalence of PostPartum Depression (PPD) symptoms defined by an Edinburg Postpartum Depression Scale (EPDS) score ≥ 11
Study Overview
Brief Summary
The objectif of the IRON-DEP Study is to assess the efficacy of intravenous (IV) versus oral iron treatment on the prevalence of postpartum depression (PPD) in women with moderate iron deficiency anemia after caesarean delivery.
Detailed Description
PPD is a frequent (10-20% of delivery) and serious condition that has a detrimental impact on both maternal and child health by altering the quality of their interactions. Moreover, it is a significant risk factor for suicide, which is the leading cause of maternal death.
The increased risk of PPD in women with postpartum anemia has been documented. Women who delivered by cesarean are particularly vulnerable to this risk as this mode of delivery is a risk factor for both postpartum anaemia and postpartum depression. Therefore, correcting anemia and preventing PPD in this population represent a major public health priority.
First line treatment recommended for iron deficiency moderate anaemia (8.0g/dL≤ Hb ≤10.0g/dL) is oral iron. However oral iron is associated with very frequent adverse effects, contributing to poor tolerance and compliance of this treatment. Actually, IV iron is indicated in women with non-severe postpartum anaemia with lack of response or intolerance to oral iron treatment. There is growing interest in the use of intravenous iron and several randomized controlled trials demonstrated that IV iron is significantly more efficient than oral iron supplementation to correct moderate postpartum anaemia and increase haemoglobin level. However, none of them compared the efficacy of IV iron versus oral iron on postpartum depression as a primary outcome.
The hypothesis of the IRON-DEP Study is that, among women with moderate postpartum iron deficiency anaemia after caesarean delivery, the prevalence of PPD symptoms at 8 weeks after delivery is lower in women treated with IV iron than in those treated with oral iron.
The IRON-DEP trial is a phase IV national multicenter comparative randomized controlled superiority open-label trial with 2 parallel groups.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Health Services Research
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Pre-inclusion criteria:
- •Age ≥18 years
- •Caesarean delivery (elective or in emergency)
- •Gestational age at delivery ≥ 32 weeks
- •8.0 g/dL ≤ postoperative Hb level ≤ 10.0 g/dL measured within 72 hours postpartum
- •Informed consent form signed
- •Hospitalization in the postpartum maternity ward
- •National social security coverage including AME
- •Inclusion criteria:
- •Ferritinemia ≤ 100 ng/mL OR transferrin saturation ≤ 20% measured after postoperative Hb level measurement
- •EPDS score in the immediate postpartum <13 with a "never" answer to question n°10
Exclusion Criteria
- •Stillbirth or neonatal death
- •Last body weight available before inclusion (measured at the end of pregnancy or in postpartum) < 35kg or > 100kg
- •Biermer disease
- •Hemochromatosis
- •Homozygous sickle cell disease or thalassemia
- •Chronic iron supplementation (outside pregnancy)
- •Known hypersensitivity or allergy to the studied drugs (IV or oral iron)
- •Contra-indication to the studied drugs (IV or oral iron)
- •Severe asthma (with daily background treatment)
- •Any known severe renal or liver disorder
- •Active acute infection
- •Diagnosis of schizophrenia or physical and intellectual state incompatible with a reliable self-evaluation
- •Women currently treated with medication or with Electro Convulsion Therapy (ECT) for depression or bipolar disorders
- •Participation in another clinical trial involving an intervention with the following risks:
- •A change (increase or decrease in value) in Haemoglobin measured at 2 months postpartum OR
- •A change in EPDS score measured at 2 and 6 months postpartum OR
- •A trial exploring an intervention with a specific anaphylactic risk (reported as a potential adverse events in the protocol of the other trial) administered during the postpartum hospitalization period.
- •Poor understanding of the French language
- •Legal protection (curatorship or tutorship)
Arms & Interventions
Intravenous iron
Women in the experimental arm will receive an IV iron infusion within 5 days after delivery
Oral iron
Women in the comparator arm will receive oral iron supplementation for 8 weeks after delivery
Outcomes
Primary Outcomes
Prevalence of PostPartum Depression (PPD) symptoms defined by an Edinburg Postpartum Depression Scale (EPDS) score ≥ 11
Time Frame: 8 weeks postpartum
Edinburg Postpartum Depression Scale (EPDS) wil be measured by a self-assessment questionnaire at 8 weeks. The primary measure of treatment effect will be based on the 'treatment policy' estimand: the effect will be measured by including all women who participated in the study, according to the initial randomization, regardless of the treatment they actually received or their adherence to the treatment. If the 8-week value is not observed, these participants will be included in the analysis after imputing their missing value. Secondary measures of treatment effect will be implemented based on the "principal stratum strategy" estimand: the effect will be measured in women according to the treatment they actually received and in those who achieved a compliance rate of over 80%. The estimands discussed above will be applied to all efficacy-related criteria. For safety-related criteria, only the second estimand (principal stratum strategy) will be considered.
Secondary Outcomes
- The mean Haemoglobin (Hb) level(8 weeks postpartum)
- Change in postpartum Haemoglobin (Hb) level(At Inclusion and at 8 weeks postpartum)
- The proportion of women with Haemoglobin level < 12.0 g/dL(8 weeks postpartum)
- The mean ferritinemia level(At Inclusion and at 8 weeks postpartum)
- The mean change in ferritinemia level(At Inclusion and at 8 weeks postpartum)
- The proportion of women with ferritinemia < 20 ng/mL(8 weeks postpartum)
- Mean EPDS score(8 weeks postpartum, 6 months postpartum)
- The proportions of participants with moderate depressive symptoms level defined by an EPDS ≥ 11 and <13(8 weeks postpartum, 6 months postpartum)
- The proportions of participants with high depressive symptoms level defined by an EPDS ≥13(8 weeks postpartum, 6 months postpartum)
- The mean change in EPDS score(8 weeks postpartum, 6 months postpartum)
- The need for red blood cell transfusion(From discharge to 8 weeks postpartum)
- The mean fatigue score measured by the Multidimensional Fatigue Inventory score-20 (MFI-20)(8 weeks postpartum, 6 months postpartum)
- The proportion of women with high fatigue score (MIF-20 score>15)(8 weeks postpartum, 6 months postpartum)
- The mean relative change in MFI-20 scores(8 weeks postpartum, 6 months postpartum)
- The mean score for mother and child bonding measured by the Mother to Infant Bonding Scale (MIBS)(8 weeks postpartum, 6 months postpartum)
- The proportion of women with MIBS≥2(8 weeks postpartum, 6 months postpartum)
- The proportion of breastfeeding women and mean duration for those who stopped(8 weeks postpartum, 6 months postpartum)
- The mean relative change in MIBS score(8 weeks postpartum, 6 months postpartum)
- The mean score of quality of life measured by EQ-5D-5L (European questionnaire of quality of life, 5 domains, 5 levels)(8 weeks postpartum, 6 months postpartum)
- The number of women in each group who also received the other group treatment within 8 weeks postpartum(Up to 8 weeks)
- Assessement of adverse events(From first drug administration to 8 weeks)
- Compliance to treatment for participants in the oral iron arm(8 weeks)
- Total costs of healthcare resources for medicoeconomic cost-consequence analysis(Up to 6 months postpartum)