Published in IJCP March 2021
Clinical Study
Comparative Study of Clinical Efficacy and Safety of Intravenous Iron Sucrose and Ferric Carboxymaltose in Treatment of Postpartum Iron Deficiency Anemia
March 12, 2021 | Nupur Gupta, Ritu Singh, Sangeeta Gupta, Taru Gupta, Apurva Nain, Surbhi Waghmare
     


Abstract

Background: Anemia, specifically iron deficiency anemia, is a major cause of postpartum morbidities. Oral iron is the most preferred treatment of iron deficiency. But its side effects require other modalities, including intravenous supplementation. Ferric carboxymaltose (FCM) is one such newer regime. The present study was conducted to compare clinical efficacy and safety of FCM with iron sucrose and oral ferrous sulfate. Methods: A prospective randomized controlled trial was conducted from December 2018 to May 2019 with 90 postpartum patients giving consent and satisfying inclusion criteria. The patients were divided into three groups to compare the clinical efficacy and safety of FCM with iron sucrose and oral iron. All the data was entered in MS-Excel and statistical analysis was done on SPSS 17.0. Student t-test was used to compare mean rise in hemoglobin of the patients in different groups. Results: Patients treated with FCM showed statistically significant highest rise in mean hemoglobin, followed by iron sucrose group, while oral iron group showed lowest rise. Maternal complications in FCM group were significantly lower as compared to other groups (p < 0.0001). Iron sucrose group patients also reported significantly less maternal complications as compared to oral iron supplementation. Conclusion: Intravenous FCM was found to be an effective treatment option for patients with iron deficiency anemia during postpartum period. It was also reported as the safest method when compared with intravenous ferrous sucrose and oral ferrous sulfate.

Keywords: Iron deficiency, postpartum, ferric carboxymaltose, ferrous sucrose, ferrous sulfate

Anemia (hemoglobin <12 g/dL in adult females and <11 g/dL in pregnancy) is considered to be a major cause of morbidity and mortality around the globe, specifically in the developing countries. During postpartum period, hemoglobin concentration <10 g/dL is considered as anemic. Major causes which may lead to postpartum anemia may include iron deficiency, hemodilution, anemia during pregnancy, antepartum and postpartum hemorrhages (PPH), etc.

Iron deficiency may result either from inadequate dietary intake, diseases like malaria, excessive blood loss during childbirth, parasitic infection and flaring up of physiological anemia of pregnancy, among other causes. Many maternal morbidities are observed to be associated with postpartum anemia. A few to mention are lethargy, tiredness, headaches, dizziness, postpartum depression, lactation failure and mortality. These problems are aggravated in prevailing conditions, as seen in our country.

Iron supplementation is the mainstay of treatment for iron deficiency anemia. Anemia occurring because of heavy blood loss during childbirth may easily be reversed with iron replenishment. Oral iron therapy is the most preferred and an easy mode of treatment because of its safety, effectiveness and low cost. But this is associated with certain side effects, including nausea, gastritis, vomiting, constipation, etc., which affects compliance of patients towards treatment. Parenteral iron therapy (intravenous iron replenishment) is increasingly recommended in cases where such side effects are observed. The older intravenous iron containing preparations like iron dextran have been found to be associated with episodes of anaphylaxis in 1-2% of the patients as reported by some authors. Iron sucrose and iron gluconate are free from any such reaction as they don’t have dextran moiety. But their physical character and administration rate limit their use.

Ferric carboxymaltose (FCM), which is a type I polynuclear iron (III)-hydroxide carbohydrate complex, has shown promising results among patients of iron deficiency anemia. It delivers complexed iron slowly but in controlled manner to the endogenous binding sites. Few randomized controlled trials have also proved the efficacy of FCM in improving hemoglobin status among postpartum patients with anemia, as compared to their oral counterparts.

Owing to the scarcity of such studies among north Indian population of the country, a study was carried out with the objective to compare clinical efficacy and safety of intravenous FCM and iron sucrose for treatment of postpartum iron deficiency anemia.

MATERIAL AND METHODS

A prospective randomized controlled trial was conducted at Dept. of Obstetrics and Gynecology, ESIC Model Hospital & PGIMSR, Basaidarapur, New Delhi, from December 2018 to May 2019. All the women less than 10 days after delivery with hemoglobin between ≥6 g/dL and ≤9 g/dL requiring iron supplementation, and consenting to participate, were enrolled in the study. Patients having significant vaginal bleeding in past 24 hours, having asthma, bleeding disorders, any cardiac disease, received intravenous iron treatment or red blood cells transfusion and received erythropoietin within 3 months prior to the study were excluded from the study.

Sample Size Calculations

A total of 90 participants were enrolled in the study. They were divided into three groups. Each group had 30 participants and were randomized using random number generator.

Detailed history and clinical examination of all the patients was done. Diagnosis of anemia was confirmed on peripheral blood smear and related pathological investigations. All patients were dewormed. Group A patients were given intravenous FCM 1,000 mg single dose (carboxymaltose 1,000 mg diluted in 100 mL of 0.9% normal saline given in 20-30 minutes).

Group B received iron sucrose therapy in multiple doses; 200 mg/day on Day 0, 2, 4, 6, 8; total of 1,000 mg (iron sucrose 200 mg diluted in 100 mL of 0.9% normal saline and given over 20-30 minutes). Group C patients acted as control group and were given oral iron supplementation. In all groups, Hb% was done on 0 and Day 30 of last dose of parenteral/oral iron. Side effects like headache, myalgia, arthralgia, nausea, vomiting, epigastric discomfort and anaphylactoid reactions were assessed and managed accordingly. Patients were called after 1 month for follow-up and investigations were repeated.

Rise in hemoglobin was considered primary outcome measure while complications like headache, myalgia, arthralgia, nausea, vomiting, epigastric discomfort and anaphylactoid reactions were considered as secondary outcome.

Ethical Statement and Statistical Comments

Patients were informed in detail about the study and its benefits. Written consent was taken. They were free to withdraw at any stage of the study. The study protocol was approved from Institutional Ethics Committee (IEC) of ESI-PGIMSR, Basaidarapur, New Delhi.

All the data was entered in MS-Excel and statistical analysis was done on SPSS 17.0. Student t-test was used to compare mean rise in hemoglobin of the patients of different groups.

RESULTS

A total of 90 patients were enrolled in the study with 30 patients in each of the three groups as described earlier (FCM group [A], ferrous sucrose group [B] and ferrous sulfate group [C], out of which ferrous sulfate group acted as our control group). In this prospective study, we compared clinical efficacy and safety of intravenous FCM and iron sucrose for treatment of postpartum iron deficiency anemia. There was no lost to follow-up of patients in any of the groups.

Majority of patients belonged to age group of 20-30 years in all the three groups. Age distribution was comparable among the three groups, and no significant difference was present (p > 0.05). The mean age of the patients in Group A was 25.17 ± 4.01 years; in Group B was 25.38 ± 3.07 years and in Group C was 25.31 ± 4.06 years. The mean age of marriage in Group A was 21.13 ± 2.3 years, in Group B was 21.20 ± 2.5 years while in Group C it was 21.67 ± 1.9 years, and was comparable in the three groups. Majority of patients had parity of one in all the groups and was comparable in the three groups. Majority of patients in all the groups had period of gestation in between 37 and 42 weeks at the time of delivery and there was no significant difference in relation to period of gestation among the three groups (p > 0.05). About one-third of patients had completed secondary school in all the three groups. Majority of patients belonged to middle class and there was no significant difference in relation to socioeconomic classes among the three groups (p > 0.05).

When study participants were assessed for modes of delivery, it was observed that majority (56.7% and 53.3%) of participants in Group A and B had normal vaginal delivery while Group C saw majority of participants with cesarean section as a mode of delivery (Table 1).

Table 1. Distribution of Study Participants of Various Groups According to Mode of Delivery (n = 30 in Each Group)

Groups of patients

Mode of delivery

P value

Vaginal delivery

Cesarean section

Total

Group A

17 (56.7%)

13 (43.3%)

30 (100%)

0.732*

Group B

16 (53.3%)

14 (46.7%)

30 (100%)

Group C

14 (46.7%)

16 (53.3%)

30 (100%)

*Chi-square test.

Only 6.7% of Group A patients had history of PPH, while in Group B it was 10% and in control group it was 3.3% only. The history of any medical or surgical illness in Group A was comparable to Group B (p > 0.05) and both the study groups had comparable comorbid conditions with the control Group C (p > 0.05).

Table 2 and Figure 1 shows that mean hemoglobin rise at zero day and at 30th day was highest in Group A followed by Group B and was lowest in Group C. This difference was statistically significant when compared among all the three groups (p < 0.001) as well as when groups were compared with each other. 

Table 2. Comparison of Mean Hemoglobin Rise among the Groups

 

Groups

P value

A vs. B

A vs. C

B vs. C

A (n = 30)

B (n = 30)

C (n = 30)

Mean hemoglobin rise (± SD)

3.92 ± 0.81

3.37 ± 0.87

2.77 ± 0.6

0.001

0.015

0.001

0.003

Figure 1. Comparison of mean hemoglobin rise among three groups.

Table 3 and Figure 2 shows that the maternal complications in Group A were significantly lower as compared to Group B and Group C (p < 0.001). Group B had lower maternal complication as compared to Group C but this difference was not statistically significant (p > 0.05).

Table 3. Comparison of Maternal Complications among the Groups

Maternal complication

Groups

Total (n = 90)

P value

A vs. B

A vs. C

B vs. C

A (n = 30)

B (n = 30)

C (n = 30)

Yes

3 (10%)

10 (33.3%)

14 (46.6%)

27 (30.0%)

<0.007

<0.028

<0.001

<0.291

No

27 (90%)

20 (66.6%)

16 (53.3%)

63 (70.0%)

Total

30 (100%)

30 (100%)

30 (100%)

90 (100%)

       

Figure 2. Comparison of maternal complications among three groups.

Table 4 gives details of various complications experienced by participants of different groups. Headache was reported by 02 (6.6%) of them in Group A. Joint pain and tingling sensation was the most common complication reported by 08 (26.6%) participants of Group B and transient hypotonia (46.7%) and nausea and heartburn (40%) were among common complications experienced by participants of Group C.

Table 4. Distribution of Study Participants According to Complications Experienced by Them

Groups of patients

Complications*

Nausea and heartburn

Joint pain and tingling sensation

Headache

Constipation

Transient hypotonia

Group A

00

01 (3.3%)

02 (6.6%)

00

00

Group B

00

08 (26.6%)

00

00

03 (10%)

Group C

12 (40%)

00

00

06 (20%)

14 (46.7%)

*Multiple responses by single patient.

DISCUSSION

A randomized controlled trial was conducted with a total of 90 patients (30 patients in each of three groups). In this study, we compared clinical efficacy and safety of intravenous FCM and iron sucrose for managing iron deficiency anemia during postpartum period.

When age groups of patients were assessed, it was observed that majority (72.2%) of patients belonged to age group 20-30 years and the mean age of the patients receiving FCM was 25.17 ± 4.01 years; those treated with ferrous sucrose was 25.38 ± 3.07 years and 25.31 ± 4.06 years for patients given ferrous sulfate. Similar results were reported by Rathod et al in their study in 2015 with mean age as 25.9 ± 3.57, 26.0 ± 3.66 and 25.4 ± 3.05, respectively, in the three groups. Shim et al, in their study in 2018, reported different mean age as 34.5 ± 4.8 years in the FCM group patients and 33.4 ± 4.9 in ferrous sulfate patients, in one group of their study population.

When period of gestation was assessed, majority of patients in all the three groups had it in between 37 and 42 weeks but no significant difference in relation to period of gestation among three groups was found (p > 0.05). Shim et al, in their study, reported differently with majority of the patients having gestational age 20-33 weeks across all study groups.

When study participants were assessed for modes of delivery, it was observed that majority (56.7% and 53.3%) of patients receiving FCM and iron sucrose, respectively, had normal vaginal delivery while the group receiving oral iron saw majority of participants with cesarean section as a mode of delivery. For FCM and iron sucrose group, similar results were reported by Rathod et al, but their results were different for patients receiving oral iron as there also majority of them had normal vaginal delivery.

Only 6.7% of Group A patients had history of PPH, in Group B it was 10% while in control group it was 3.3% only. These results are similar to the study by Khandale et al (2015) reporting 5.78% of the total patients reporting PPH and differed from the study conducted by Rathod el al in 2015, where PPH was reported among 24%, 21% and 27% of the patients of FCM, ferrous sucrose and ferrous sulfate groups, respectively.

Mean hemoglobin rise from baseline at 30th day of follow-up was highest in FCM group followed by patients receiving ferrous sucrose and patients having oral ferrous sulfate had lowest rise in mean hemoglobin. This difference of mean rise of hemoglobin among three groups was statistically significant (p < 0.001). Seid et al also reported in their study in 2017 significantly greater rise in mean hemoglobin levels among patients receiving FCM (p < 0.001), as also Rathod et al, in their study, who observed significantly highest rise in mean hemoglobin level at 2 and 6 weeks of follow-up (p < 0.001) in patients receiving FCM.

Maternal complications in patients receiving FCM were significantly lower as compared to ferrous sucrose and oral ferrous sulfate groups (p < 0.0001). Headache was reported by 6.6% of the patients in Group A. Joint pain and tingling sensation was the most common complication reported by 26.6% participants of Group B and transient hypotonia (46.7%) and nausea and heartburn (40%) were among common complications experienced by participants of Group C. Similar results were reported by Shim et al in their study in 2018, where FCM group had less adverse events as compared to ferrous sulfate group patients.

Patients receiving ferrous sucrose also had lower maternal complications as compared to those receiving oral ferrous sulfate, though this was not statistically significant (p > 0.05). Abhilashini et al in their study in 2014 also reported similar results with oral iron group patients having more side effects.

CONCLUSION

Intravenous FCM given as a 1,000 mg single dose was found to be an effective modality for treatment of postpartum anemia with patients showing significantly highest rise in mean hemoglobin in FCM group as compared to intravenous ferrous sucrose and oral ferrous sulfate (control) groups. Also, FCM was found to be safest across all three treatments with least number of adverse effects.

SUGGESTED READING

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