Iron Deficiency Anemia of PregnancyNCT03706638
Daily vs Intermittent Iron Therapy in Pregnancy
A study testing Ferrous Sulfate in people with Iron Deficiency Anemia of Pregnancy, run by UConn Health at 1 site in United States.
Trial summary
This is a randomized non inferiority trial to evaluate the response to iron therapy in the standard daily vs. intermittent (three-four times a week on nonconsecutive days) groups by using hematological markers (hemoglobin, hematocrit, transferrin, hepcidin, ferritin, human soluble transferrin receptor). Read more about this study
- Who is it for?
- Ages 18 to 50 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Iron Deficiency Anemia of Pregnancy
- What is being tested?
- Ferrous Sulfate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Oct 2018to 23 Mar 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Pregnant women who are not underweight (BMI < 18.5 kg/m2)
- Reproductive-aged women 18-50
- Singleton Pregnancy.
- Patients undergoing third trimester blood work from 26-28 weeks.
- Women who have had previously normal first-trimester blood work (hemoglobin, hematocrit, MCV) without any evidence of existing anemia.
- Pregnant women with anemia designated with hemoglobin concentration less than 11 g/dL or hematocrit less than 33%
- No pre-existing iron deficiency anemia or not already on iron supplementation.
Who cannot join
- Women with medical problems known to affect iron metabolism or homeostasis
- Women with existing thalassemias or anemias.
- Women with abnormal bloodwork indicating anemia earlier in the pregnancy.
- Women are already taking iron supplementation during the pregnancy for treatment of iron deficiency anemia.
- Chronic illness is influencing iron absorption.
- Underlying malabsorption disease.
Show all 9Show fewer
- History of bariatric surgery.
- Severe anemia with maternal hemoglobin levels less than 6 g/dL
- Preterm Labor, PPROM, signs of infection.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Daily vs. Intermittent Iron Therapy in Iron Deficient Pregnant Patients: A Randomized Noninferiority Trial
This is a randomized non inferiority trial to evaluate the response to iron therapy in the standard daily vs. intermittent (three-four times a week on nonconsecutive days) groups by using hematological markers (hemoglobin, hematocrit, transferrin, hepcidin, ferritin, human soluble transferrin receptor). The secondary outcome is to evaluate gastrointestinal discomfort and adherence to therapy between two treatment groups.
Read the detailed description
The Centers for Disease Control and Prevention estimates that as many as 8 million American women of childbearing age are iron deficient. In a typical singleton gestation, the maternal need for iron averages close to 1000 mg. Of this 300 mg is for the fetus and placenta; 500 mg for maternal hemoglobin mass expansion; and 200 mg that is normally shed through the gut, urine, and skin. The total amount of 1000 mg considerably exceeds the iron stores of most women and results in iron-deficiency anemia unless iron supplementation is given.
Correction of anemia and restitution of iron stores can be accomplished with simple iron compounds-ferrous sulfate, fumarate or gluconate. Oral iron is an effective treatment for iron deficiency anemia and is inexpensive, safe and widely available.
In the past, a standard approach to the treatment of iron deficiency anemia was oral ferrous sulfate 325 mg (65 mg elemental iron) spaced in 3 doses each day for a total daily dose of 195 mg elemental iron. However, recent absorption studies concluded that maximal absorption of iron occurs with a dose in the range of 40 to 80 mg of elemental iron daily. This study was done in non pregnant iron-deficient women. Greater doses do not result in more iron absorption and are associated with more side effects. The findings of this study have been implemented by many into various areas of medicine.
Daily oral supplementation in pregnant women has been a long-standing, cost-effective recommended intervention both in the public health and clinical fields. However, adherence to daily iron and folic acid supplementation still faces challenges. Data from national surveys from 46 countries (2003 to 2009) indicate that about 52% to 75% of mothers receive any iron tablets during pregnancy, and the duration of supplementation is usually short.
According to a study by Khalafallah, the side effects or oral iron therapy including gastrointestinal disturbances characterized by colicky pain, nausea, vomiting, diarrhea, and constipation occur in about 50% of a patient taking iron preparations, and the investigators estimate that their patients have similar complaints and intolerances.
Many pregnant women taking oral iron, especially at doses greater than 30 mg daily of elemental iron daily, have gastrointestinal side effects, which cause them to discontinue the iron therapy. Taking iron supplementation on an intermittent basis may help to reduce gastrointestinal side effects and improve iron stores.
In the United States, the oral iron preparation of ferrous sulfate is often used to replete iron-deficient women. To the investigators' knowledge, studies have not been performed to evaluate daily vs. oral intermittent oral iron therapy in the United States, which has a different nutritional status and access to health care than other countries.
This study will randomize patients to the standard therapy: taking iron ferrous sulfate 325 mg (daily) by mouth once a day by mouth or intermittent therapy of taking ferrous sulfate 325 mg three- four times a week on alternating days. Hematological markers (hemoglobin, hematocrit, transferrin, hepcidin, ferritin, human soluble transferrin receptor), will be assessed prior to treatment and after treatment is completed.
- Conditions
- Iron Deficiency Anemia of Pregnancy
- Being tested
- Ferrous Sulfate
- Keywords
- Iron Deficiency Anemia, Pregnancy, Side Effects
- Medical subject headings
- Anemia, Iron-Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ferrous SulfateDietary supplement
Patients would be randomized to either taking ferrous sulfate daily or every other day (on non consecutive days).
| Study group | Role | What they receive |
|---|---|---|
| Daily | Other | Patients randomized to this arm will take ferrous sulfate 325 mg every day. Receives: Dietary Supplement: Ferrous Sulfate |
| Intermittent (Every other day) | Other | Patient's randomized to this arm will take ferrous sulfate 325 mg every other day. Receives: Dietary Supplement: Ferrous Sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hematologic values assessed for anemia
Hematologic values of hemoglobin, hematocrit, transferrin, hepcidin, human soluble transferrin receptor and ferritin.
Measured: This will be measured 4-6 weeks after starting treatment.
Secondary outcomes (1)
Scores on self report survey of gastrointestinal adverse side effects after oral iron supplementation
The study adapts a previously validated questionnaire to capture side effects normally associated with oral iron supplementation. A likert scale is used with intermediate anchors to quantify side effects as absent, mild, moderate or severe. Absent was 0 symptoms experienced. Mild was less than 3 times a week, moderate was 3-5 times a week and severe was every single day. The possible total score is 60 with higher numbers representing more severe symptoms. These numbers will be compared between the two treatment groups.
Measured: Side effects will be reviewed every 2 weeks for a period of 4-6 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2018
- Study start25 Oct 2018
- Primary completion23 Mar 2020
- Study completion23 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Iron Deficiency Anemia of PregnancyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized Noninferiority Trial
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- UConn Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Winston Campbell, UConn Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03706638
- Sponsor's protocol ID
- 18-181-1
- Status last verified
- Apr 2020
- First submitted
- 11 Oct 2018
- Last updated
- 21 Apr 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Looker AC, Dallman PR, Carroll MD, Gunter EW, Johnson CL. Prevalence of iron deficiency in the United States. JAMA. 1997 Mar 26;277(12):973-6. doi: 10.1001/jama.1997.03540360041028.
PubMed 9091669American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 95: anemia in pregnancy. Obstet Gynecol. 2008 Jul;112(1):201-7. doi: 10.1097/AOG.0b013e3181809c0d.
PubMed 18591330Khalafallah AA, Dennis AE. Iron deficiency anaemia in pregnancy and postpartum: pathophysiology and effect of oral versus intravenous iron therapy. J Pregnancy. 2012;2012:630519. doi: 10.1155/2012/630519. Epub 2012 Jun 26.
PubMed 22792466Daru J, Allotey J, Pena-Rosas JP, Khan KS. Serum ferritin thresholds for the diagnosis of iron deficiency in pregnancy: a systematic review. Transfus Med. 2017 Jun;27(3):167-174. doi: 10.1111/tme.12408. Epub 2017 Apr 20.
PubMed 28425182van den Broek NR, Letsky EA, White SA, Shenkin A. Iron status in pregnant women: which measurements are valid? Br J Haematol. 1998 Dec;103(3):817-24. doi: 10.1046/j.1365-2141.1998.01035.x.
PubMed 9858238Koenig MD, Tussing-Humphreys L, Day J, Cadwell B, Nemeth E. Hepcidin and iron homeostasis during pregnancy. Nutrients. 2014 Aug 4;6(8):3062-83. doi: 10.3390/nu6083062.
PubMed 25093277Cook JD, Flowers CH, Skikne BS. The quantitative assessment of body iron. Blood. 2003 May 1;101(9):3359-64. doi: 10.1182/blood-2002-10-3071. Epub 2003 Jan 9.
PubMed 12521995Stoffel NU, Cercamondi CI, Brittenham G, Zeder C, Geurts-Moespot AJ, Swinkels DW, Moretti D, Zimmermann MB. Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials. Lancet Haematol. 2017 Nov;4(11):e524-e533. doi: 10.1016/S2352-3026(17)30182-5. Epub 2017 Oct 9.
PubMed 29032957F. Gary Cunningham, John C. Hauth, Kenneth J. Leveno, Larry Gilstrap Iii, Steven L. Bloom, & Katharine D. Wenstrom. (2010). Williams obstetrics. Williams Obstetrics (pp. 1081).
Pena-Rosas JP, De-Regil LM, Dowswell T, Viteri FE. Intermittent oral iron supplementation during pregnancy. Cochrane Database Syst Rev. 2012 Jul 11;7(7):CD009997. doi: 10.1002/14651858.CD009997.
PubMed 22786531Tolkien Z, Stecher L, Mander AP, Pereira DI, Powell JJ. Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis. PLoS One. 2015 Feb 20;10(2):e0117383. doi: 10.1371/journal.pone.0117383. eCollection 2015.
PubMed 25700159
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Daily vs. Intermittent Iron Therapy in Iron Deficient Pregnant Patients: A Randomized Noninferiority Trial
- ClinicalTrials.gov ID
- NCT03706638
- Acronym / sponsor ID
- 18-181-1
- Conditions
- Iron Deficiency Anemia of Pregnancy
- Keywords
- Iron Deficiency Anemia, Pregnancy, Side Effects
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- UConn HealthUniversity, hospital or other
- Study start
- 25 Oct 2018 (actual)
- Primary completion
- 23 Mar 2020 (actual)
- Study completion
- 23 Mar 2020 (actual)
- First posted
- 16 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized non inferiority trial to evaluate the response to iron therapy in the standard daily vs. intermittent (three-four times a week on nonconsecutive days) groups by using hematological markers (hemoglobin, hematocrit, transferrin, hepcidin, ferritin, human soluble transferrin receptor). The secondary outcome is to evaluate gastrointestinal discomfort and adherence to therapy between two treatment groups.
Detailed description
The Centers for Disease Control and Prevention estimates that as many as 8 million American women of childbearing age are iron deficient. In a typical singleton gestation, the maternal need for iron averages close to 1000 mg. Of this 300 mg is for the fetus and placenta; 500 mg for maternal hemoglobin mass expansion; and 200 mg that is normally shed through the gut, urine, and skin. The total amount of 1000 mg considerably exceeds the iron stores of most women and results in iron-deficiency anemia unless iron supplementation is given.
Correction of anemia and restitution of iron stores can be accomplished with simple iron compounds-ferrous sulfate, fumarate or gluconate. Oral iron is an effective treatment for iron deficiency anemia and is inexpensive, safe and widely available.
In the past, a standard approach to the treatment of iron deficiency anemia was oral ferrous sulfate 325 mg (65 mg elemental iron) spaced in 3 doses each day for a total daily dose of 195 mg elemental iron. However, recent absorption studies concluded that maximal absorption of iron occurs with a dose in the range of 40 to 80 mg of elemental iron daily. This study was done in non pregnant iron-deficient women. Greater doses do not result in more iron absorption and are associated with more side effects. The findings of this study have been implemented by many into various areas of medicine.
Daily oral supplementation in pregnant women has been a long-standing, cost-effective recommended intervention both in the public health and clinical fields. However, adherence to daily iron and folic acid supplementation still faces challenges. Data from national surveys from 46 countries (2003 to 2009) indicate that about 52% to 75% of mothers receive any iron tablets during pregnancy, and the duration of supplementation is usually short.
According to a study by Khalafallah, the side effects or oral iron therapy including gastrointestinal disturbances characterized by colicky pain, nausea, vomiting, diarrhea, and constipation occur in about 50% of a patient taking iron preparations, and the investigators estimate that their patients have similar complaints and intolerances.
Many pregnant women taking oral iron, especially at doses greater than 30 mg daily of elemental iron daily, have gastrointestinal side effects, which cause them to discontinue the iron therapy. Taking iron supplementation on an intermittent basis may help to reduce gastrointestinal side effects and improve iron stores.
In the United States, the oral iron preparation of ferrous sulfate is often used to replete iron-deficient women. To the investigators' knowledge, studies have not been performed to evaluate daily vs. oral intermittent oral iron therapy in the United States, which has a different nutritional status and access to health care than other countries.
This study will randomize patients to the standard therapy: taking iron ferrous sulfate 325 mg (daily) by mouth once a day by mouth or intermittent therapy of taking ferrous sulfate 325 mg three- four times a week on alternating days. Hematological markers (hemoglobin, hematocrit, transferrin, hepcidin, ferritin, human soluble transferrin receptor), will be assessed prior to treatment and after treatment is completed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized Noninferiority Trial
| Arm | Type | Receives |
|---|---|---|
| Daily | Other | Dietary Supplement: Ferrous SulfatePatients randomized to this arm will take ferrous sulfate 325 mg every day. |
| Intermittent (Every other day) | Other | Dietary Supplement: Ferrous SulfatePatient's randomized to this arm will take ferrous sulfate 325 mg every other day. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Pregnant women who are not underweight (BMI < 18.5 kg/m2)
- Reproductive-aged women 18-50
- Singleton Pregnancy.
- Patients undergoing third trimester blood work from 26-28 weeks.
- Women who have had previously normal first-trimester blood work (hemoglobin, hematocrit, MCV) without any evidence of existing anemia.
Key exclusion criteria (9 listed)
- Women with medical problems known to affect iron metabolism or homeostasis
- Women with existing thalassemias or anemias.
- Women with abnormal bloodwork indicating anemia earlier in the pregnancy.
- Women are already taking iron supplementation during the pregnancy for treatment of iron deficiency anemia.
- Chronic illness is influencing iron absorption.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ferrous SulfatePatients would be randomized to either taking ferrous sulfate daily or every other day (on non consecutive days). | Dietary supplement | Daily, Intermittent (Every other day) |
Primary outcome
Hematologic values assessed for anemia
Time frame: This will be measured 4-6 weeks after starting treatment.
Hematologic values of hemoglobin, hematocrit, transferrin, hepcidin, human soluble transferrin receptor and ferritin.
1 secondary outcome
Scores on self report survey of gastrointestinal adverse side effects after oral iron supplementation
Time frame: Side effects will be reviewed every 2 weeks for a period of 4-6 weeks.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2020.
- Background: PubMed 9091669Looker AC, Dallman PR, Carroll MD, Gunter EW, Johnson CL. Prevalence of iron deficiency in the United States. JAMA. 1997 Mar 26;277(12):973-6. doi: 10.1001/jama.1997.03540360041028.
- Background: PubMed 18591330American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 95: anemia in pregnancy. Obstet Gynecol. 2008 Jul;112(1):201-7. doi: 10.1097/AOG.0b013e3181809c0d.
- Background: PubMed 22792466Khalafallah AA, Dennis AE. Iron deficiency anaemia in pregnancy and postpartum: pathophysiology and effect of oral versus intravenous iron therapy. J Pregnancy. 2012;2012:630519. doi: 10.1155/2012/630519. Epub 2012 Jun 26.
- Background: PubMed 28425182Daru J, Allotey J, Pena-Rosas JP, Khan KS. Serum ferritin thresholds for the diagnosis of iron deficiency in pregnancy: a systematic review. Transfus Med. 2017 Jun;27(3):167-174. doi: 10.1111/tme.12408. Epub 2017 Apr 20.
- Background: PubMed 9858238van den Broek NR, Letsky EA, White SA, Shenkin A. Iron status in pregnant women: which measurements are valid? Br J Haematol. 1998 Dec;103(3):817-24. doi: 10.1046/j.1365-2141.1998.01035.x.
- Background: PubMed 25093277Koenig MD, Tussing-Humphreys L, Day J, Cadwell B, Nemeth E. Hepcidin and iron homeostasis during pregnancy. Nutrients. 2014 Aug 4;6(8):3062-83. doi: 10.3390/nu6083062.
- Background: PubMed 12521995Cook JD, Flowers CH, Skikne BS. The quantitative assessment of body iron. Blood. 2003 May 1;101(9):3359-64. doi: 10.1182/blood-2002-10-3071. Epub 2003 Jan 9.
- Background: PubMed 29032957Stoffel NU, Cercamondi CI, Brittenham G, Zeder C, Geurts-Moespot AJ, Swinkels DW, Moretti D, Zimmermann MB. Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials. Lancet Haematol. 2017 Nov;4(11):e524-e533. doi: 10.1016/S2352-3026(17)30182-5. Epub 2017 Oct 9.
- Results publicationF. Gary Cunningham, John C. Hauth, Kenneth J. Leveno, Larry Gilstrap Iii, Steven L. Bloom, & Katharine D. Wenstrom. (2010). Williams obstetrics. Williams Obstetrics (pp. 1081).
- Results publication: PubMed 22786531Pena-Rosas JP, De-Regil LM, Dowswell T, Viteri FE. Intermittent oral iron supplementation during pregnancy. Cochrane Database Syst Rev. 2012 Jul 11;7(7):CD009997. doi: 10.1002/14651858.CD009997.
- Results publication: PubMed 25700159Tolkien Z, Stecher L, Mander AP, Pereira DI, Powell JJ. Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis. PLoS One. 2015 Feb 20;10(2):e0117383. doi: 10.1371/journal.pone.0117383. eCollection 2015.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ferrous Sulfate in people with Iron Deficiency Anemia of Pregnancy, run by UConn Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hematologic values assessed for anemia (time frame: This will be measured 4-6 weeks after starting treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03706638, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2020.