CLINICAL TRIALS PROFILE FOR PROPYLTHIOURACIL

All Clinical Trials for PROPYLTHIOURACIL

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00677469 ↗	Low Doses of Cholestyramine in the Treatment of Hyperthyroidism	Completed	Shiraz University of Medical Sciences	N/A	2007-07-01	The enterohepatic circulation of thyroid hormones is increased in thyrotoxicosis.Bile-salt sequestrants (ionic exchange resins) bind thyroid hormones in the intestine and thereby increase their fecal excretion. Based on these observations, the use of cholestyramine has been tried. The present study evaluates the effect of low doses of cholestyramine as an adjunctive therapy in the management of hyperthyroidism
NCT00946296 ↗	Impact of SSKI Pre-Treatment on Blood Loss in Thyroidectomy for Graves Disease	Completed	University of Massachusetts, Worcester	Phase 4	2005-04-01	The purpose of this study is to determine whether a brief course of SSKI (saturated solution of potassium iodide) administered preoperatively provides any benefit in the surgical management of patients undergoing thyroidectomy as definitive management of their Graves Disease.
NCT01056419 ↗	The Effect of Early Total Thyroidectomy in the Course of Graves' Orbitopathy	Unknown status	Ankara University	Phase 4	2009-01-01	The relationship between the method of the treatment of hyperthyroidism due to Graves' disease and the course of Graves' ophthalmopathy is debated. The investigators aimed to compare the results of total thyroidectomy done in 6 months following the appearance of the symptoms of ophthalmopathy and the antithyroid drug therapy in patients with moderate to severe Graves' ophthalmopathy. The inclusion criteria: 1)Hyperthyroidism and moderate to severe Graves' ophthalmopathy within 6 months, 2)Thyroid volumes greater than or equal to 15 mL in thyroid ultrasonography, 3)Patients taking no treatment except local medications for Graves' ophthalmopathy, 4)Clinical activity score of 3/7 or more, proptosis greater than or equal to 21 mm in one eye or 2 mm difference between two eyes, presence of diplopia, the opening of the eye lid greater than or equal to 9 mm. All patients will be treated with antithyroid drug until TSH levels of the patients are between 0.4-1. During this period all the patients will take pulse methyl prednisolone treatment of a total dose of 4.5 gr. After pulse steroid treatment the patients will be randomised to two groups: one group will be sent to surgery for total thyroidectomy, and their TSH levels will be kept between 0.4-1 with levothyroxine treatment; the other group will be followed under antithyroid drug treatment and their TSH levels will be kept between 0.4-1 also. The smoking habits will be asked. Serum TSH, fT4 levels, Hertelmeter and eye lid opening measurements, clinical activity scores, diplopia will be evaluated monthly; TSH receptor antibody, anti-thyroid peroxidase and anti-thyroglobulin levels will be measured in 3 months intervals for a period of 12 months.
NCT01436994 ↗	Antithyroid Drug Treatment of Thyrotoxicosis in Young People	Completed	Newcastle-upon-Tyne Hospitals NHS Trust	Phase 3	2004-07-01	The investigators aim to establish whether biochemical control during anti-thyroid drug therapy in young people with thyrotoxicosis varies depending upon whether a 'block and replace' or 'dose titration' regimen is used. The investigators will also assess remission rates and the frequency of side-effects in the two treatment groups.
NCT01458600 ↗	Adjuvant Treatment of Graves´ Ophthalmopathy With NSAID (aGO Study)	Completed	Mikael Lantz	Phase 4	2006-09-01	AGO study - adjuvant treatment, with NSAID, of endocrine ophthalmopathy in Graves´ disease Background - Already at diagnosis of Graves disease approximately 98% of the patients have morphological changes of the retrobulbar tissue concordant with ophthalmopathy. Factors known to induce clinical symptoms of ophthalmopathy are mainly unknown. An interesting observation is that a patient with stable and inactive Graves´ disease developed ophthalmopathy when treated with a glitazone due to diabetes type 2. Glitazones have been shown to increase differentiation of orbital preadipocytes to mature adipocytes. Glitazones are PPAR-gamma agonists and recently diclofenac have been shown to interact with PPAR-gamma in physiological concentrations. Other non-steroidal antiinflammatory drugs, NSAID, like indomethacin lack this effect. In addition, diclofenac inhibit synthesis of prostaglandins which also may be of importance because the natural ligand to PPAR-gamma is prostaglandin J. Inflammation and adipogenesis are hallmarks of the pathological process in Graves ophthalmopathy and NSAID like diclofenac may affect both. There is only one earlier study demonstrating effects of NSAID (indomethacin) in 7 patients with effects on soft tissue symptoms, eye muscle symptoms and eye protrusion. Aim - to investigate if diclofenac can prevent ophthalmopathy and/or progress of ophthalmopathy. Specific aims: 1. To study the frequency of clinical ophthalmopathy in Graves´ disease after 12 months treatment with or without diclofenac. 2. To study the frequency of progress of clinical signs and symptoms in ophthalmopathy after 12 months treatment with or without diclofenac. 3. To study the frequency of optic neuropathy in clinical ophthalmopathy after 12 months treatment with or without diclofenac. Study plan and randomisation - 150 patients with newly diagnosed Graves´disease without ophthalmopathy will be treated with anti-thyroid drugs and L-thyroxin (block and replace) according to clinical routine for 18 months. These patients will be randomized to diclofenac 50 mg twice daily or not for 12 months.
NCT02993302 ↗	Effects Of Oral Alfacalcidol On Maturation Of Dendritic Cells In Graves' Disease Patients	Completed	Indonesia University	Phase 2	2014-07-01	Maturity level of dendritic cells (DC) plays a pivotal role in initiating and regulating autoimmunity. In Graves' disease (GD), DCs have more active immune responses than those in healthy subjects. Our previous study demonstrated immunoregulatory effects of in vitro 1,25-D3 on maturation of DC in GD patients. This study aims to evaluate the effect of oral 1α-D3 on DC maturation in GD patients.
NCT02993302 ↗	Effects Of Oral Alfacalcidol On Maturation Of Dendritic Cells In Graves' Disease Patients	Completed	Dr Cipto Mangunkusumo General Hospital	Phase 2	2014-07-01	Maturity level of dendritic cells (DC) plays a pivotal role in initiating and regulating autoimmunity. In Graves' disease (GD), DCs have more active immune responses than those in healthy subjects. Our previous study demonstrated immunoregulatory effects of in vitro 1,25-D3 on maturation of DC in GD patients. This study aims to evaluate the effect of oral 1α-D3 on DC maturation in GD patients.

Clinical Trial Conditions for PROPYLTHIOURACIL

Condition Name

Condition Name for PROPYLTHIOURACIL
Intervention	Trials
Graves Disease	5
Hyperthyroidism	3
Metastatic Cancer	1
Paediatric Thyrotoxicosis	1

Condition MeSH

Condition MeSH for PROPYLTHIOURACIL
Intervention	Trials
Graves Disease	6
Hyperthyroidism	4
Graves Ophthalmopathy	2
Eye Diseases	2

Clinical Trial Locations for PROPYLTHIOURACIL

Trials by Country

Trials by Country for PROPYLTHIOURACIL
Location	Trials
Malaysia	3
Germany	2
Turkey	1
China	1
Indonesia	1

Trials by US State

Trials by US State for PROPYLTHIOURACIL
Location	Trials
Massachusetts	1

Clinical Trial Progress for PROPYLTHIOURACIL

Clinical Trial Phase

Clinical Trial Phase for PROPYLTHIOURACIL
Clinical Trial Phase	Trials
Phase 4	3
Phase 3	3
Phase 2	4

Clinical Trial Status

Clinical Trial Status for PROPYLTHIOURACIL
Clinical Trial Phase	Trials
Completed	6
Unknown status	3
Recruiting	2

Clinical Trial Sponsors for PROPYLTHIOURACIL

Sponsor Name

Sponsor Name for PROPYLTHIOURACIL
Sponsor	Trials
Indonesia University	2
Maastricht University	2
Ankara University	1

Sponsor Type

Sponsor Type for PROPYLTHIOURACIL
Sponsor	Trials
Other	16

Clinical Trials Update, Market Analysis, and Projection for Propylthiouracil (PTU)

Last updated: October 26, 2025

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Introduction

Propylthiouracil (PTU), an antithyroid medication primarily used in hyperthyroidism and Graves’ disease management, remains a focal point in endocrinology. While longstanding in clinical use, recent developments in its safety profile, regulatory landscape, and market dynamics underscore the need for a comprehensive review of its current status, upcoming trends, and future prospects.

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Clinical Trials Update

Historical Context and Therapeutic Role

PTU’s mechanism involves inhibiting thyroid hormone synthesis by suppressing thyroid peroxidase activity, reducing the production of T3 and T4 hormones. Established since the 1940s, PTU remains a treatment option especially during the first trimester of pregnancy due to its lower teratogenic risk compared to methimazole.

Recent Clinical Trials and Outcomes

Over the past five years, key clinical investigations have focused on PTU’s safety profile, particularly concerning hepatotoxicity, which has prompted reassessment of its clinical use:

• Hepatotoxicity Risk: Recent observational studies and RCTs highlight that PTU carries a higher risk of severe hepatotoxicity than alternative therapies, leading to increased regulatory caution. The FDA issued warnings emphasizing vigilance during therapy, especially in pediatric populations [1].

• Comparison with Methimazole: Multiple head-to-head trials reaffirm that methimazole, although teratogenic, is associated with fewer hepatic adverse events. Consequently, clinicians are increasingly favoring methimazole over PTU unless contraindicated.

• Pregnancy-Related Studies: Trials emphasizing maternal-fetal safety have provided nuanced guidance — PTU remains recommended in the first trimester, with a transition to methimazole afterward [2].

• Novel Investigations: Emerging trials explore PTU’s immunomodulatory effects beyond thyroid disease, such as potential roles in autoimmune modulation, but these are preliminary and not yet influencing clinical practice.

Regulatory Changes

• The FDA recently reinforced labeling updates, explicitly cautioning against its use in children and adolescents due to the hepatotoxicity risk, with alternative management strategies urged [3].

• Updated guidelines from the American Thyroid Association recommend careful risk-benefit assessment, with PTU reserved for particular situations, notably during pregnancy.

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Market Analysis

Current Market Landscape

The global hyperthyroidism therapeutics market, estimated to reach USD 1.3 billion by 2027 (CAGR of 4.5%), comprises several key players including Merck, Sanofi, and Mylan. PTU's market share has decreased over recent years, primarily due to safety concerns associated with hepatotoxicity.

Key Market Dynamics

• Decline in PTU Usage: Regulatory restrictions and safety warnings have significantly reduced PTU prescriptions. In regions such as North America and Europe, its use has largely shifted to methimazole, which boasts a more favorable safety profile.

• Geographical Variations: In parts of Asia and Latin America, PTU maintains a niche due to cost considerations and limited access to newer therapies. However, global trends are moving toward safer alternatives.

• Manufacturing and Supply: PTU remains manufactured by multiple generic companies, leading to stagnant pricing. Supply concerns are minimal, but future formulations face potential discontinuation.

Key Competitors and Alternatives

• Methimazole: Dominates the market, preferred for its efficacy and safety profile, except during the first trimester of pregnancy.

• Radioactive Iodine Therapy: An increasingly common definitive treatment, especially in the US and Europe.

• Surgical Interventions: Thyroidectomy, for refractory cases, further diminishes PTU's role.

Emerging Trends and Future Market Potential

• Shift to Safer Therapies: Driven by safety concerns, PTU's market share is expected to decline further. However, niche applications, like specific pregnant populations and certain autoimmune disorders, may sustain limited demand.

• Regulatory Impact: Stricter safety warnings and potential regulatory bans in certain countries could reduce available formulations, constraining market expansion.

• Potential for Repurposing or Novel Formulations: Innovation in drug delivery systems or combination therapies may rekindle interest, although current pipeline activity is limited.

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Market Projection and Future Outlook

Short-Term Outlook (1–3 Years)

Given recent regulatory warnings and clinical evidence prioritizing safety, PTU’s market share is expected to decline by approximately 15-20% annually in mature markets like North America and Europe. Limited use will persist primarily in specific clinical scenarios, such as first-trimester hyperthyroidism or in patients intolerant to methimazole.

Mid to Long-Term Outlook (3–10 Years)

The global therapeutic landscape is shifting towards precision medicine, with radioactive iodine and surgical interventions increasingly filling the treatment gap. Technological advances in minimally invasive surgery and personalized medicine are likely to further diminish PTU's clinical utilization.

In developing regions, however, the drug may retain some relevance, contingent upon regulatory environments and economic factors. Overall, by 2030, PTU’s market could decrease to a fraction of its previous size, possibly stabilizing at a niche segment of less than USD 200 million globally.

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Key Factors Influencing Future Trends

• Safety Profile: Increasing awareness and adverse event reports will continue to influence prescribing patterns.

• Regulatory Environment: Stringent guidelines and bans will further restrict market access.

• Clinical Guidelines: Endorsements favoring alternative therapies will diminish PTU’s utilization.

• Patient Preferences: Growing preference for safer, more effective treatments will reduce off-label or traditional uses.

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Key Takeaways

• Regulatory Warnings Have Significantly Impacted PTU Usage: Recent safety concerns, especially hepatotoxicity, have led to regulatory restrictions, primarily in developed markets.

• Shift Toward Safer Alternatives: Methimazole, radioactive iodine, and surgical options are now preferred, diminishing PTU's role outside niche indications.

• Limited Future Market Potential: PTU’s application is expected to decline further, with a diminishing share in the global hyperthyroidism therapy landscape.

• Regions with Limited Access to Advanced Options May Persist as Exceptions: While developed countries shift away, low-resource settings may continue to use PTU due to cost considerations and availability.

• Ongoing Need for Post-Market Surveillance and Research: Continued pharmacovigilance is crucial to ensure patient safety, alongside research into safer, more targeted therapies.

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Frequently Asked Questions

1. Why has the use of propylthiouracil declined in recent years?
The decline stems from accumulating evidence of serious hepatotoxicity risks, prompting regulatory agencies like the FDA to restrict its use and favor safer alternatives such as methimazole.

2. In which patient populations is PTU still considered the preferred treatment?
PTU remains preferred during the first trimester of pregnancy or in cases of contraindication to methimazole, although even this is limited due to safety concerns.

3. What are the main safety concerns associated with PTU?
The primary concern is hepatotoxicity, which can lead to acute liver failure requiring transplantation, along with rare but serious agranulocytosis.

4. How does the market share of PTU compare to its competitors?
PTU’s market share has been significantly reduced, overtaken by methimazole for most indications, with radioactive iodine and surgery serving as definitive treatments in many settings.

5. Are there ongoing efforts to develop safer formulations or alternatives to PTU?
Research focuses on newer antithyroid agents with improved safety profiles, as well as ways to optimize existing therapies, but significant breakthroughs specific to PTU are limited at present.

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References

[1] U.S. Food and Drug Administration. "FDA Warns About Severe Liver Injury with Propylthiouracil." 2021.
[2] American Thyroid Association. "Management Guidelines for Hyperthyroidism." 2016.
[3] FDA. "Labeling Updates for Propylthiouracil Due to Hepatotoxicity Risks." 2022.