Clinical trial NCT06833788: Treatment of Anaemia After Caesarean with Intravenous Versus Oral Iron and Postpartum Depression
Official title: Treatment of Anaemia After Caesarean with Intravenous Versus Oral Iron and Postpartum Depression: a Multicentric Randomized Open-labelled Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Postpartum Depression (PPD)
Keywords: Postpartum depression (PPD)
Postpartum anaemia
Caesarean
Intravenous (IV) iron therapy
Oral iron therapy
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2025-02-19
Enrollment: 2860
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

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.

Implementation of the study :

* 24 french maternity units will be participating
* Women who delivered by cesarean admitted in the postpartum maternity ward, with postpartum anaemia will be screened to check the inclusion and exclusion criteria.
* The investigator will inform the eligible patient about the protocol and obtain the written consent
* The randomization will take place during the hospitalization for caesarean delivery and will be stratified on the centre and on the initial severity of post-partum anemia (according to the postpartum hemoglobin level).
* IV iron will be administered during hospitalization and participants in the oral iron group will start their treatment during their hospitalization for 8 weeks treatment.
* A follow up visit at 8 weeks postpartum will be planned at the maternity unit for all participants
* All participants will fill in self-assessment questionnaires (online or paper form) at inclusion, 8 weeks and 6 months postpartum follow up.

Eligibility 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 \<11 with a "never" answer to question n°10

Exclusion Criteria:

* Stillbirth or neonatal death
* Body weight \< 35kg or \> 100kg at the end of pregnancy
* 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)

Primary outcomes:
measure: Prevalence of PostPartum Depression (PPD) symptoms defined by an Edinburg Postpartum Depression Scale (EPDS) score ≥ 11
timeFrame: 8 weeks postpartum
Secondary outcomes:
measure: The mean Haemoglobin (Hb) level
timeFrame: 8 weeks postpartum
measure: Change in postpartum Haemoglobin (Hb) level
timeFrame: At Inclusion and at 8 weeks postpartum
measure: The proportion of women with Haemoglobin level < 12.0 g/dL
timeFrame: 8 weeks postpartum
measure: The mean ferritinemia level
timeFrame: At Inclusion and at 8 weeks postpartum
measure: The mean change in ferritinemia level
timeFrame: At Inclusion and at 8 weeks postpartum
measure: The proportion of women with ferritinemia < 20 ng/mL
timeFrame: 8 weeks postpartum
measure: Mean EPDS score
timeFrame: 8 weeks postpartum, 6 months postpartum
measure: The proportions of participants with moderate depressive symptoms level defined by an EPDS ≥ 11 and <13
timeFrame: 8 weeks postpartum, 6 months postpartum
measure: The proportions of participants with high depressive symptoms level defined by an EPDS ≥13
timeFrame: 8 weeks postpartum, 6 months postpartum
measure: The mean change in EPDS score
timeFrame: 8 weeks postpartum, 6 months postpartum
measure: The need for red blood cell transfusion
timeFrame: From discharge to 8 weeks postpartum
measure: The mean fatigue score measured by the Multidimensional Fatigue Inventory score-20 (MFI-20)
timeFrame: 8 weeks postpartum, 6 months postpartum
measure: The proportion of women with high fatigue score (MIF-20 score>15)
timeFrame: 8 weeks postpartum, 6 months postpartum
measure: The mean relative change in MFI-20 scores
timeFrame: 8 weeks postpartum, 6 months postpartum
measure: The mean score for mother and child bonding measured by the Mother to Infant Bonding Scale (MIBS)
timeFrame: 8 weeks postpartum, 6 months postpartum
measure: The proportion of women with MIBS≥2
timeFrame: 8 weeks postpartum, 6 months postpartum
measure: The proportion of breastfeeding women and mean duration for those who stopped
timeFrame: 8 weeks postpartum, 6 months postpartum
measure: The mean relative change in MIBS score
timeFrame: 8 weeks postpartum, 6 months postpartum
measure: The mean score of quality of life measured by EQ-5D-5L (European questionnaire of quality of life, 5 domains, 5 levels)
timeFrame: 8 weeks postpartum, 6 months postpartum
measure: The number of women in each group who also received the other group treatment within 8 weeks postpartum
timeFrame: Up to 8 weeks
measure: Assessement of adverse events
timeFrame: From first drug administration to 8 weeks
measure: Compliance to treatment for participants in the oral iron arm
timeFrame: 8 weeks
measure: Total costs of healthcare resources for medicoeconomic cost-consequence analysis
timeFrame: Up to 6 months postpartum
Other outcomes:
Locations:
city: Paris
country: France
facility: CHU Armand -Trousseau, AP-HP Service d'anesthésie-réanimation chirurgicale
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Marie-Pierre BONNET, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Assistance Publique - Hôpitaux de Paris
name: Catherine DENEUX-THARAUX, MD, PhD
role: STUDY_DIRECTOR
References: