Anemia, Pregnancy Complications
Conditions
Keywords
iron deficiency anemia, pregnancy, third trimester, intravenous iron, efficacy, a randomized trial, Female, Ferric Compounds/therapeutic use*, Infusions, Intravenous, Hematologic/therapy*
Brief summary
The purpose of this study is to compare the efficacy of body iron storage replenishment between low dose intravenous iron and oral iron in late pregnancy.
Detailed description
Despite routine antenatal oral iron supplementation, the prevalence of iron deficiency anemia (IDA) in the 3rd trimester of pregnancy in developing countries remains high. Apparently, intravenous iron sucrose appears to be safe and efficient in treating within a short period. From literature review, no study of intravenous iron for IDA treatment has been carried out in the third trimester of pregnancy. This research aims to compare the efficacy of body iron storage replenishment at 3 weeks as labor may take place at this point in some women. In this study,500 mg intravenous iron has been given weekly instead of every other day for the sake of patient's convenience in the hope that parenteral iron may become another alternative for treatment of pregnant women with iron deficiency anemia who have difficulties or failures with oral iron.
Interventions
DRUGFerli-6® (Continental Pharm co., ltd.)
In the O-group, women had to take 3 ferrous fumarate tablets (Ferli-6®) everyday with a total of 200 mg of elemental iron per day from 33 weeks gestation until delivery. Emphasizing and monitoring for compliance to the treatment protocol were carried out.
DRUGVenofer® (Vifor AG, St. Gallen, Switzerland)
Women in the IV-group received 500 mg iron sucrose (Venofer®, Vifor International AG, St. Gallen, Switzerland) divided into three weekly administrations. Two doses of 200 mg iron sucrose were given at 33 and 34 weeks gestation while the remaining (100 mg) was infused at gestation of 35 weeks. Thereafter, women in this group received no further iron therapy until delivery. In preparation, 200 mg of iron sucrose was diluted into 100 ml of 0.9% saline solution.
Sponsors
Vifor Pharma
Mahidol University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age 18-45 years old 2. Singleton pregnancy at 32 weeks gestation 3. Having anemia in the third trimester according to World Health Organization, namely, with a hemoglobin level of \< 11 g/dL or hematocrit of \< 33% 4. Having no underlying disease such as hypertension, gestational diabetes mellitus, heart disease, peptic ulcer, etc. 5. Having no history of allergy to iron containing medication 6. Having no history or other allergic conditions or asthma 7. Having no thalassemia disease, for examples: B thalassemia major, hemoglobin E/ B thalassemia, homozygous hemoglobin E, Hemoglobin H, AE Bart disease, and EF Bart disease. Pregnant women who have iron deficiency anemia and are thalassemia carriers such as A-thalassemia 1, B-thalassemia, or less severe Hb E/ B thalassemia are able to enter the study. 8. Having no history of bleeding tendency 9. Having no history of blood transfusion within the prior 120 days 10. Having no history of delivery before 36 weeks gestation 11. Giving consent and having signed the consent form for this study
Exclusion criteria
1. Stool exam revealed parasitic infestation 2. C-reactive protein \> 3 mg/L 3. Serum ferritin \> 15 mcg/L
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Serum Ferritin Level | 3 weeks after intervention |
Secondary
| Measure | Time frame |
|---|---|
| Haemoglobin Level | 3 weeks after intervention |
Countries
Thailand
Participant flow
Recruitment details
This trial was conducted at Maternal Fetal Medicine Unit, Siriraj Hospital between September 2008 and December 2009. Singleton pregnant women aged 18-45 years old at GA of 32 weeks with Hb level \< 11.0 g/dL, serum ferritin levels \< 15 µg/L and CRP of \< 20 mg/L with negative stool examination for parasitic infection were recruited into the study.
Participants by arm
| Arm | Count |
|---|---|
| Iron Sucrose, Venofer, Intravenous Drug Initially, there were 194 subjects enrolled but 114 cases were excluded from the study. Among those, 104 cases did not meet the inclusion criteria and 10 cases refused to take part. A total of 80 eligible patients were equally randomised and allocated in to 2 groups of intravenous sucrose complex-group (ISC) and oral ferrous fuamrate-group (OFF) . At GA of 36 weeks, there were 4 cases of the OFF-group and 2 cases of the ISC-group lost to follow-up. At delivery, there were 50 patients remained in the study whereas 30 patients were excluded from statistical analysis due to losing to follow-up (16 cases), delivery at other hospitals (10 cases) and preterm deliveries (4 cases). | 40 |
| Ferrous Fumarate, Ferri-6, Oral Tablet Initially, there were 194 subjects enrolled but 114 cases were excluded from the study. Among those, 104 cases did not meet the inclusion criteria and 10 cases refused to take part. A total of 80 eligible patients were equally randomised and allocated in to 2 groups of intravenous sucrose complex-group (ISC) and oral ferrous fuamrate-group (OFF) . At GA of 36 weeks, there were 4 cases of the OFF-group and 2 cases of the ISC-group lost to follow-up. At delivery, there were 50 patients remained in the study whereas 30 patients were excluded from statistical analysis due to losing to follow-up (16 cases), delivery at other hospitals (10 cases) and preterm deliveries (4 cases). | 40 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| At Delivery (GA of 39 Weeks) | Lost to Follow-up | 9 | 7 |
| At Delivery (GA of 39 Weeks) | preterm delivery, delivery elesewhere | 6 | 8 |
| At Gestational Age of 36 Weeks | Lost to Follow-up | 2 | 4 |
Baseline characteristics
| Characteristic | Iron Sucrose, Venofer, Intravenous Drug | Ferrous Fumarate, Ferri-6, Oral Tablet | Total |
|---|---|---|---|
| Age, Continuous | 24.3 years STANDARD_DEVIATION 4.9 | 24.9 years STANDARD_DEVIATION 5.9 | 24.6 years STANDARD_DEVIATION 5.4 |
| Body mass index | 19.7 kg/sq.m STANDARD_DEVIATION 3.4 | 20.1 kg/sq.m STANDARD_DEVIATION 2.2 | 19.9 kg/sq.m STANDARD_DEVIATION 2.9 |
| Body weight | 48.1 kg STANDARD_DEVIATION 8.1 | 50.2 kg STANDARD_DEVIATION 6.6 | 49.2 kg STANDARD_DEVIATION 7.4 |
| C-reactive protein | 3.7 mg/L STANDARD_DEVIATION 2 | 4.0 mg/L STANDARD_DEVIATION 2.3 | 3.9 mg/L STANDARD_DEVIATION 2.2 |
| Sex: Female, Male Female | 40 Participants | 40 Participants | 80 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 40 | 0 / 40 |
| serious Total, serious adverse events | 0 / 40 | 0 / 40 |
Outcome results
Primary
Serum Ferritin Level
Time frame: 3 weeks after intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iron Sucrose, Venofer, Intravenous Drug | Serum Ferritin Level | 136.1 µg/dL | Standard Deviation 55 |
| Ferrous Fumarate, Ferri-6, Oral Tablet | Serum Ferritin Level | 28.3 µg/dL | Standard Deviation 14.8 |
Secondary
Haemoglobin Level
Time frame: 3 weeks after intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iron Sucrose, Venofer, Intravenous Drug | Haemoglobin Level | 10.6 g/dL | Standard Deviation 0.6 |
| Ferrous Fumarate, Ferri-6, Oral Tablet | Haemoglobin Level | 10.2 g/dL | Standard Deviation 1 |