CLINICAL TRIALS PROFILE FOR FERROUS SULFATE; FOLIC ACID

505(b)(2) Clinical Trials for ferrous sulfate; folic acid

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
OTC	NCT02189889 ↗	Active Preoperative Anemia Management in Patients Undergoing Cardiac Surgery	Terminated	AMAG Pharmaceuticals, Inc.	Phase 1/Phase 2	2013-04-09	Anemia which is a decreased blood count or lower than normal hemoglobin (hgb), is a major health problem for patients having heart surgery. Hemoglobin is the part of our blood that carries oxygen from the lungs to the rest of the body. Anemia that is present before surgery, called preoperative anemia, is a risk factor for an increased chance of morbidity (illness) and/or mortality (death) after heart surgery. It is also an important indicator of blood transfusion necessity. Recent clinical research investigations done to study preoperative anemia suggest a blood transfusion can damage the immune system (the system that protects us from disease) which can lead to infection, organ dysfunction (especially of the heart, kidney, brain), prolonged hospital stays, as well as increased supplies, resources and cost in surgical patients. Comprehensive anemia management can reduce or eliminate the need for blood transfusions and provide better outcomes after surgery. Therefore, controlling anemia before surgery is extremely important, and could be a lifesaving measure. This pilot, feasibility study is being done for several reasons. First of all, it will test the the safety and effectiveness of using a short-course of two medications, erythropoietin (EPO) and Feraheme (iron given intravenously [IV]), to increase hemoglobin levels in order to improve preoperative anemia, reduce transfusions and lower postoperative complications in anemic patients undergoing heart surgery. Secondly, findings will be used to design a large randomized controlled trial (RCT). The RCT will establish a protocol to actively manage anemia before surgery, thus reducing transfusions during surgery and improving recovery afterwards. It will also help identify valuable information regarding what needs to be done for timely completion of the planned RCT. EPO is a medication approved by the Food and Drug Administration (FDA) used to treat anemia in patients with certain conditions in order to reduce blood transfusions. And although approved for use during surgery, it has not been FDA approved for use in cardiac (heart) or vascular (blood vessels, including veins and arteries) surgery. Common side effects include nausea, vomiting, itching, headache, injection site pain, chills, deep vein thrombosis (blood clot), cough, and changes in blood pressure (BP). Feraheme is an iron replacement product approved for the treatment of low iron anemia in adult patients. It may cause serious allergic reactions, including anaphylaxis (severe, whole body allergic reaction), as well as low BP and excessive iron storage. Patients meeting all eligibility requirements that consent to participate will be randomized into the study. Randomization is being placed by chance (like a flip of a coin) into one of two study groups, the treatment group or the control group. There is an equal chance of being placed into either group, which will be done by a computer. 1. The Treatment Group will receive a 300 unit (U) per kilogram (kg) injection of EPO and a 510 milligram (mg) IV infusion of Feraheme 7-28 days before the day of surgery. And again 1-7 days before the day of surgery, a second dose of both of these medications will be given. The third dose, of EPO only, will be administered 2 days after surgery. Before initiating a dose or giving a subsequent dose, laboratory parameters will be measured to assess the hemoglobin level and response to the medication. If blood values increase too rapidly or are too high, the meds will not be started or, if already dosed, they will not be given again. 2. The Control Group will receive no preoperative intervention for anemia unless lab results show iron deficiency anemia. The control group will be screened for the presence of iron deficiency anemia by evaluating blood laboratory values drawn during the baseline or preoperative visit. If lab results indicate iron deficiency anemia, over-the-counter oral iron will be recommended, to take until the day of surgery. In doing so, patients may benefit by potentially reducing the need for blood transfusions. Data will be collected from all participants from the preoperative visits throughout the admission, including lab results, medications, vital signs, information about the procedure, transfusions, and any problems or adverse events.
OTC	NCT02189889 ↗	Active Preoperative Anemia Management in Patients Undergoing Cardiac Surgery	Terminated	University of Texas Southwestern Medical Center	Phase 1/Phase 2	2013-04-09	Anemia which is a decreased blood count or lower than normal hemoglobin (hgb), is a major health problem for patients having heart surgery. Hemoglobin is the part of our blood that carries oxygen from the lungs to the rest of the body. Anemia that is present before surgery, called preoperative anemia, is a risk factor for an increased chance of morbidity (illness) and/or mortality (death) after heart surgery. It is also an important indicator of blood transfusion necessity. Recent clinical research investigations done to study preoperative anemia suggest a blood transfusion can damage the immune system (the system that protects us from disease) which can lead to infection, organ dysfunction (especially of the heart, kidney, brain), prolonged hospital stays, as well as increased supplies, resources and cost in surgical patients. Comprehensive anemia management can reduce or eliminate the need for blood transfusions and provide better outcomes after surgery. Therefore, controlling anemia before surgery is extremely important, and could be a lifesaving measure. This pilot, feasibility study is being done for several reasons. First of all, it will test the the safety and effectiveness of using a short-course of two medications, erythropoietin (EPO) and Feraheme (iron given intravenously [IV]), to increase hemoglobin levels in order to improve preoperative anemia, reduce transfusions and lower postoperative complications in anemic patients undergoing heart surgery. Secondly, findings will be used to design a large randomized controlled trial (RCT). The RCT will establish a protocol to actively manage anemia before surgery, thus reducing transfusions during surgery and improving recovery afterwards. It will also help identify valuable information regarding what needs to be done for timely completion of the planned RCT. EPO is a medication approved by the Food and Drug Administration (FDA) used to treat anemia in patients with certain conditions in order to reduce blood transfusions. And although approved for use during surgery, it has not been FDA approved for use in cardiac (heart) or vascular (blood vessels, including veins and arteries) surgery. Common side effects include nausea, vomiting, itching, headache, injection site pain, chills, deep vein thrombosis (blood clot), cough, and changes in blood pressure (BP). Feraheme is an iron replacement product approved for the treatment of low iron anemia in adult patients. It may cause serious allergic reactions, including anaphylaxis (severe, whole body allergic reaction), as well as low BP and excessive iron storage. Patients meeting all eligibility requirements that consent to participate will be randomized into the study. Randomization is being placed by chance (like a flip of a coin) into one of two study groups, the treatment group or the control group. There is an equal chance of being placed into either group, which will be done by a computer. 1. The Treatment Group will receive a 300 unit (U) per kilogram (kg) injection of EPO and a 510 milligram (mg) IV infusion of Feraheme 7-28 days before the day of surgery. And again 1-7 days before the day of surgery, a second dose of both of these medications will be given. The third dose, of EPO only, will be administered 2 days after surgery. Before initiating a dose or giving a subsequent dose, laboratory parameters will be measured to assess the hemoglobin level and response to the medication. If blood values increase too rapidly or are too high, the meds will not be started or, if already dosed, they will not be given again. 2. The Control Group will receive no preoperative intervention for anemia unless lab results show iron deficiency anemia. The control group will be screened for the presence of iron deficiency anemia by evaluating blood laboratory values drawn during the baseline or preoperative visit. If lab results indicate iron deficiency anemia, over-the-counter oral iron will be recommended, to take until the day of surgery. In doing so, patients may benefit by potentially reducing the need for blood transfusions. Data will be collected from all participants from the preoperative visits throughout the admission, including lab results, medications, vital signs, information about the procedure, transfusions, and any problems or adverse events.

All Clinical Trials for ferrous sulfate; folic acid

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00120822 ↗	Folic Acid Supplementation in Gambian Primigravidae	Completed	Department of State for Health and Social Welfare, The Gambia	Phase 3	2002-07-01	Supplementation with folic acid and iron is recommended for pregnant women in order to prevent them from developing anemia. In malaria endemic areas of Africa, the World Health Organization (WHO) now recommends that pregnant women should also be given sulfadoxine-pyrimethamine (SP) once a month after quickening to protect them against malaria which is especially harmful during pregnancy. However, folic acid is an antagonist of SP so there is a possibility that giving folic acid with SP could interfere with the ability of the latter to provide protection against malaria. To investigate this possibility Gambian primigravidae with malaria parasitemia have been given SP and folic acid at the same time or on separate occasions two weeks apart and the ability of SP to cure the malaria infection investigated.
NCT00120822 ↗	Folic Acid Supplementation in Gambian Primigravidae	Completed	London School of Hygiene and Tropical Medicine	Phase 3	2002-07-01	Supplementation with folic acid and iron is recommended for pregnant women in order to prevent them from developing anemia. In malaria endemic areas of Africa, the World Health Organization (WHO) now recommends that pregnant women should also be given sulfadoxine-pyrimethamine (SP) once a month after quickening to protect them against malaria which is especially harmful during pregnancy. However, folic acid is an antagonist of SP so there is a possibility that giving folic acid with SP could interfere with the ability of the latter to provide protection against malaria. To investigate this possibility Gambian primigravidae with malaria parasitemia have been given SP and folic acid at the same time or on separate occasions two weeks apart and the ability of SP to cure the malaria infection investigated.
NCT00120822 ↗	Folic Acid Supplementation in Gambian Primigravidae	Completed	Medical Research Council Unit, The Gambia	Phase 3	2002-07-01	Supplementation with folic acid and iron is recommended for pregnant women in order to prevent them from developing anemia. In malaria endemic areas of Africa, the World Health Organization (WHO) now recommends that pregnant women should also be given sulfadoxine-pyrimethamine (SP) once a month after quickening to protect them against malaria which is especially harmful during pregnancy. However, folic acid is an antagonist of SP so there is a possibility that giving folic acid with SP could interfere with the ability of the latter to provide protection against malaria. To investigate this possibility Gambian primigravidae with malaria parasitemia have been given SP and folic acid at the same time or on separate occasions two weeks apart and the ability of SP to cure the malaria infection investigated.

Clinical Trial Conditions for ferrous sulfate; folic acid

Condition Name

Condition Name for ferrous sulfate; folic acid
Intervention	Trials
Iron Deficiency Anemia	23
Anemia	19
Iron-deficiency	6

Condition MeSH

Condition MeSH for ferrous sulfate; folic acid
Intervention	Trials
Anemia	56
Anemia, Iron-Deficiency	55
Deficiency Diseases	19

Clinical Trial Locations for ferrous sulfate; folic acid

Trials by Country

Trials by Country for ferrous sulfate; folic acid
Location	Trials
United States	124
Egypt	6
United Kingdom	3
Pakistan	3
Puerto Rico	3

Trials by US State

Trials by US State for ferrous sulfate; folic acid
Location	Trials
Texas	12
Pennsylvania	11
New York	7
Michigan	7
California	6

Clinical Trial Progress for ferrous sulfate; folic acid

Clinical Trial Phase

Clinical Trial Phase for ferrous sulfate; folic acid
Clinical Trial Phase	Trials
PHASE4	2
PHASE3	3
PHASE1	1

Clinical Trial Status

Clinical Trial Status for ferrous sulfate; folic acid
Clinical Trial Phase	Trials
Completed	41
Recruiting	24
Not yet recruiting	6

Clinical Trial Sponsors for ferrous sulfate; folic acid

Sponsor Name

Sponsor Name for ferrous sulfate; folic acid
Sponsor	Trials
American Regent, Inc.	7
AMAG Pharmaceuticals, Inc.	7
Luitpold Pharmaceuticals	6

Sponsor Type

Sponsor Type for ferrous sulfate; folic acid
Sponsor	Trials
Other	113
Industry	35
NIH	3

Last updated: May 26, 2026

Ferrous Sulfate + Folic Acid Clinical Trials Update, Market Analysis, and 2025–2035 Forecast

Executive summary: Ferrous sulfate plus folic acid is a long-established, low-cost combination for iron-deficiency anemia (IDA) prevention and treatment during pregnancy and where folate deficiency risk exists. The market is driven by maternal health demand, government supplementation programs, and chronic IDA prevalence. Clinical-trial activity is concentrated in comparative bioavailability/tolerability studies, pregnancy outcomes, and dose-form optimization (immediate-release tablets, chewables, liquid suspensions, and fixed-dose combinations). Commercial outlook through 2035 is steady-to-modest growth, constrained by the drug’s generic commoditization, limited patent-protected innovation, and pricing pressure.

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What clinical trials are running for ferrous sulfate and folic acid (IDA and pregnancy anemia)?

Featured snippet: Clinical development for ferrous sulfate + folic acid largely stays in the categories of bioequivalence, tolerability, and pregnancy/hematologic response endpoints, rather than late-stage novel mechanisms.

Trial types that dominate the pipeline

1. Bioequivalence and formulation studies

   • Tablet vs tablet comparisons, including different iron salt forms (still “ferrous sulfate” as the active), coating technologies, and excipient systems.
   • Liquid and chewable equivalents for adherence and pediatric/pregnancy use.

2. Comparative efficacy in hematologic response

   • Time to hemoglobin improvement, ferritin response, and transferrin saturation.
   • Safety endpoints focused on GI tolerability (nausea, constipation, abdominal discomfort).

3. Pregnancy and postpartum outcomes

   • Maternal hemoglobin recovery, iron indices, and folate status.
   • Adherence and discontinuation rates are key because tolerability drives persistence.

Common inclusion populations

• Pregnant patients at risk of IDA or already diagnosed with anemia.
• Postpartum patients with low iron stores.
• Patients with nutritional anemia where folate deficiency contributes to macrocytosis or mixed anemia patterns.

Trial endpoints regulators and payers track

• Hemoglobin change from baseline (e.g., mg/dL or g/L).
• Ferritin and transferrin saturation recovery.
• Maternal and neonatal safety signals (where studies are designed with obstetric endpoints).
• Discontinuation due to adverse events, dosing schedule adherence, and dose interruption rates.

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Are there new mechanism-of-action trials, or is the pipeline mostly reformulation?

Featured snippet: For ferrous sulfate + folic acid, the development pipeline is mostly reformulation and comparative clinical evidence, not new pharmacology.

Where “novelty” still shows up

• Dose strategies: altered dosing frequency to improve tolerability while maintaining iron absorption targets.
• Product format: chewable tablets, flavored suspensions, and pediatric-compatible presentations.
• Gastrointestinal tolerability mitigation: excipient systems aimed at reducing GI side effects that lead to nonadherence.
• Real-world adherence studies: shorter interventional studies that measure dosing compliance and discontinuation.

What is usually not seen

• Large Phase 3 programs for “new” therapeutics with distinct MOA, because the active ingredients are established generics with off-patent status in most geographies.

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Which formulations of ferrous sulfate + folic acid are studied in current clinical research?

Featured snippet: Clinical research concentrates on fixed-dose tablets and alternative oral dosage forms to improve adherence.

Common dosage forms in study designs

• Immediate-release tablets (fixed-dose combinations).
• Chewable tablets (adherence in pregnancy and for patients with swallowing difficulty).
• Oral liquids/suspensions (dose flexibility for pediatrics and obstetric titration).
• Extended-release approaches (less common for this exact combination, but occasionally assessed to reduce GI effects).

What companies test in comparative studies

• Tablet hardness, dissolution profiles, and gastric pH interaction.
• Iron absorption metrics under standardized fasting vs fed conditions.
• Folate serum or red blood cell folate status as a secondary endpoint.

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What do clinical trial results imply for dosing, adherence, and safety?

Featured snippet: The dominant clinical issue is tolerability-driven adherence, not efficacy failure.

Typical safety profile seen in comparative studies

• GI adverse events are the main drivers:
  • Constipation
  • Nausea and dyspepsia
  • Abdominal discomfort
• A “tolerability advantage” is often tied to excipient systems, formulation dissolution rate control, or dosing schedule changes.

Adherence is often the differentiator

• Trials frequently show that fixed-dose combination regimens simplify the regimen and improve folate co-therapy uptake.
• Real-world adherence improvements depend on side effect burden and dosing frequency.

Efficacy consistency

• Hematologic improvement is typically achieved if patients adhere to dosing and baseline deficiency is present.
• Ferritin recovery is slower than hemoglobin change, which influences duration-of-therapy counseling.

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Market analysis: How big is the ferrous sulfate + folic acid market and what drives demand?

Featured snippet: Demand is anchored in maternal health and IDA prevalence with a structural tailwind from public supplementation programs.

Primary demand drivers

• High prevalence of iron deficiency in reproductive-age women.
• Pregnancy supplementation policies and antenatal guideline adoption.
• Chronic anemia in resource-limited settings where low-cost oral therapy is preferred.
• OTC and clinician prescribing patterns that favor familiar, inexpensive regimens.

Key commercial dynamics

• Generic competition keeps prices low.
• Value differentiation tends to come from:
  • availability and distribution coverage
  • packaging (unit-of-use blisters, multi-month packs)
  • adherence-friendly formats
  • brand positioning in private markets

Pricing and gross margin implications

• Expect limited margin upside without a differentiated formulation or national tender advantages.
• Growth comes from volume expansions and contract wins, not from premium pricing.

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How is the market segmented (pregnancy, IDA treatment, pediatrics, OTC)?

Featured snippet: The largest segments are typically pregnancy/antenatal supplementation and iron deficiency anemia treatment; pediatrics follows with weight-based dosing flexibility.

Segment lenses used by commercial teams

1. Indication

   • Pregnancy anemia and prevention
   • IDA treatment
   • Mixed anemia where folate supplementation is clinically indicated

2. Patient segment

   • Adults (women of reproductive age)
   • Pregnant patients
   • Pediatrics (where liquid or chewable presentations are used)

3. Channel

   • Hospitals and antenatal clinics
   • Retail pharmacy (often OTC-adjacent in some markets)
   • Government procurement and public health programs

4. Geography

   • High maternal deficiency burden markets
   • Markets with strong guideline compliance and public supplementation infrastructure

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What is the competitive landscape for ferrous sulfate + folic acid?

Featured snippet: Competition is dominated by generic manufacturers plus regional brands; differentiation is mostly product form and procurement scale.

Competitive patterns

• Local brands in tender-heavy geographies.
• Multi-country generic portfolios where bioequivalence supports broad market access.
• Tender winners often outperform due to:
  • supply reliability
  • packaging compliance
  • regulatory dossier quality
  • price-indexed contract terms

Where differentiation can still matter

• Chewable and liquid products improve adherence.
• Packaging and dosing instructions reduce missed doses.

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What is the forecast for ferrous sulfate + folic acid through 2035?

Featured snippet: Base-case outlook is stable-to-moderate unit growth with flat-to-slow revenue growth under ongoing pricing pressure.

Revenue projection logic (typical for commodities)

• Units grow with maternal health and IDA prevalence.
• Average selling price (ASP) compresses due to generics and tender competition.
• Revenue CAGR typically tracks inflation plus modest volume gains, not premium innovation.

Scenario framing used in investment models

1. Base case
   • Steady volume growth.
   • Continued price erosion to a stable low-ASP range.
2. Upside
   • Expansion of supplementation programs or improved adherence leading to longer duration-of-therapy coverage.
   • Faster penetration of better-tolerability formats.
3. Downside
   • Further price cuts from tender restructurings.
   • Substitution toward alternative oral iron products with better tolerability profiles in specific formularies.

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Do alternatives like other oral irons or IV iron erode share?

Featured snippet: Share can shift, but ferrous sulfate + folic acid remains entrenched where guidelines and procurement frameworks mandate low-cost oral therapy.

Substitution vectors

• Other oral iron salts or iron polysaccharide formulations in some markets.
• Intravenous iron in severe or nonresponsive IDA where rapid repletion is prioritized.
• Combination products with different folate dosing strengths, depending on local guideline conventions.

Net effect in most models

• Substitution reduces growth rate at the margin, but does not eliminate the underlying supplementation demand base.

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What regulatory status matters for market entry and updates?

Featured snippet: Regulatory pathways in most markets treat these actives as established products, so the focus is on bioequivalence and pharmaceutical quality rather than clinical efficacy packages.

What regulators generally emphasize

• Dissolution and absorption consistency for oral iron salts.
• Stability and shelf-life (oxidation and potency of both iron and folate).
• Bioequivalence evidence for generics.
• Labeling alignment with pregnancy supplementation guidance.

Key compliance themes

• Accurate iron content labeling.
• Consistent folate dosing and stability.
• Clear dosing guidance for prenatal use and anemia treatment duration.

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How strong is the patent estate for ferrous sulfate + folic acid?

Featured snippet: The patent estate is typically weak or expired for the actives and standard fixed-dose combinations, shifting the competitive advantage to formulation trade secrets, regulatory exclusivities (where any exist), and brand relationships.

Where any IP might exist in practice

• Specific fixed-dose ratios plus unique formulation/excipient systems.
• New dosage forms, extended-release behavior (less common for this exact combo), or manufacturing process improvements.
• Packaging, patient support programs, or trademark-based brand differentiation.

Implication for investors and litigators

• R&D risk is mainly regulatory and manufacturing execution rather than exclusivity enforcement.

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What generic entry risks exist for ferrous sulfate + folic acid?

Featured snippet: Generic entry risk is low from an exclusivity standpoint because the market is largely already generic.

Real risks that still matter commercially

• Supply-chain disruption affecting tender continuity.
• Quality deviations leading to batch recalls or regulator action.
• Inconsistent dosing strength labeling that triggers compliance failures.
• Patent or regulatory exclusivity surprises tied to specific combinations or formulations in select jurisdictions, though this is not typical.

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What does a typical litigation or settlement landscape look like for this drug class?

Featured snippet: Litigation is usually less prominent than in novel specialty drugs; when it occurs, it often relates to formulation or generic labeling disputes in specific jurisdictions.

Most common dispute categories in commodity oral combos

• Bioequivalence study sufficiency and generic labeling alignment.
• Intellectual property disputes tied to specific formulation claims where still in force.
• Tender bid challenges, not patent-centric.

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Key takeaways on strategy, development, and commercial positioning

• Clinical development for ferrous sulfate + folic acid is dominated by comparative bioavailability, tolerability, and adherence evidence, with pregnancy hematologic endpoints.
• Market growth is driven by maternal health demand and IDA prevalence, not by mechanistic innovation.
• Forecasts through 2035 are typically stable-to-moderate unit growth with pricing pressure and limited revenue upside without supply advantages.
• Competitive advantage comes from scale, distribution, reliable tender performance, and adherence-friendly formats.
• Patent leverage is generally limited; commercial success depends on execution rather than exclusivity.

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FAQs

1) Does ferrous sulfate + folic acid treat all causes of anemia?

It treats iron deficiency anemia and supports folate correction where folate deficiency contributes. It does not address anemia driven by non-iron etiologies without appropriate diagnosis.

2) What side effects most impact adherence in ferrous sulfate + folic acid?

GI adverse events such as constipation, nausea, and dyspepsia are the main adherence limiters across typical oral iron studies.

3) Are chewable or liquid formulations clinically different from tablets?

Clinical differentiation is usually modest but can improve adherence. Comparative studies focus on dissolution, tolerability, and hematologic response.

4) When is intravenous iron considered instead of oral ferrous sulfate + folic acid?

In severe, rapidly progressive, or oral-intolerant cases where clinicians aim for faster repletion, IV iron can be used depending on guidelines and patient factors.

5) How do prenatal dosing guidelines affect market demand?

Guidelines that recommend routine supplementation create a predictable baseline demand that supports steady volume even in highly generic markets.

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References

1. World Health Organization (WHO). Guideline: Daily iron and folic acid supplementation in pregnant women. WHO.
2. NIH Office of Dietary Supplements. Folate Fact Sheet for Health Professionals. National Institutes of Health.
3. NIH Office of Dietary Supplements. Iron Fact Sheet for Health Professionals. National Institutes of Health.