CLINICAL TRIALS PROFILE FOR NITROFURANTOIN; NITROFURANTOIN, MACROCRYSTALLINE

All Clinical Trials for nitrofurantoin; nitrofurantoin, macrocrystalline

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02384200 ↗	A Randomized Trial of Preoperative Prophylactic Antibiotics Prior to Kidney Stone Surgery (Percutaneous Nephrolithotomy [PCNL])	Completed	Dartmouth-Hitchcock Medical Center	Phase 4	2015-03-01	When patients are going to have surgery to remove large kidney stones (percutaneous nephrolithotomy [PCNL]), it is not clear whether the patients benefit from a course of prophylactic preoperative oral antibiotics; currently both the use of prophylactic preoperative oral antibiotics and no prophylactic oral antibiotics are considered to be within standard-of-care. This study will randomize patients to preoperative prophylactic antibiotics or no antibiotics to determine if the use of preoperative prophylactic antibiotics decreases the postoperative risk of localized urinary tract infection (UTI) and/or systemic infection that started in the urinary tract (sepsis or urosepsis).
NCT02384200 ↗	A Randomized Trial of Preoperative Prophylactic Antibiotics Prior to Kidney Stone Surgery (Percutaneous Nephrolithotomy [PCNL])	Completed	Duke University	Phase 4	2015-03-01	When patients are going to have surgery to remove large kidney stones (percutaneous nephrolithotomy [PCNL]), it is not clear whether the patients benefit from a course of prophylactic preoperative oral antibiotics; currently both the use of prophylactic preoperative oral antibiotics and no prophylactic oral antibiotics are considered to be within standard-of-care. This study will randomize patients to preoperative prophylactic antibiotics or no antibiotics to determine if the use of preoperative prophylactic antibiotics decreases the postoperative risk of localized urinary tract infection (UTI) and/or systemic infection that started in the urinary tract (sepsis or urosepsis).
NCT02384200 ↗	A Randomized Trial of Preoperative Prophylactic Antibiotics Prior to Kidney Stone Surgery (Percutaneous Nephrolithotomy [PCNL])	Completed	Mayo Clinic	Phase 4	2015-03-01	When patients are going to have surgery to remove large kidney stones (percutaneous nephrolithotomy [PCNL]), it is not clear whether the patients benefit from a course of prophylactic preoperative oral antibiotics; currently both the use of prophylactic preoperative oral antibiotics and no prophylactic oral antibiotics are considered to be within standard-of-care. This study will randomize patients to preoperative prophylactic antibiotics or no antibiotics to determine if the use of preoperative prophylactic antibiotics decreases the postoperative risk of localized urinary tract infection (UTI) and/or systemic infection that started in the urinary tract (sepsis or urosepsis).
NCT02384200 ↗	A Randomized Trial of Preoperative Prophylactic Antibiotics Prior to Kidney Stone Surgery (Percutaneous Nephrolithotomy [PCNL])	Completed	New York University	Phase 4	2015-03-01	When patients are going to have surgery to remove large kidney stones (percutaneous nephrolithotomy [PCNL]), it is not clear whether the patients benefit from a course of prophylactic preoperative oral antibiotics; currently both the use of prophylactic preoperative oral antibiotics and no prophylactic oral antibiotics are considered to be within standard-of-care. This study will randomize patients to preoperative prophylactic antibiotics or no antibiotics to determine if the use of preoperative prophylactic antibiotics decreases the postoperative risk of localized urinary tract infection (UTI) and/or systemic infection that started in the urinary tract (sepsis or urosepsis).

Clinical Trial Conditions for nitrofurantoin; nitrofurantoin, macrocrystalline

Condition Name

Condition Name for nitrofurantoin; nitrofurantoin, macrocrystalline
Intervention	Trials
Nephrolithiasis	2
Urinary Tract Infections	2
Sepsis	1
Urinary Tract Infection (UTI)	1

Condition MeSH

Condition MeSH for nitrofurantoin; nitrofurantoin, macrocrystalline
Intervention	Trials
Urinary Tract Infections	3
Nephrolithiasis	2
Kidney Calculi	2
Sepsis	1

Clinical Trial Locations for nitrofurantoin; nitrofurantoin, macrocrystalline

Trials by Country

Trials by Country for nitrofurantoin; nitrofurantoin, macrocrystalline
Location	Trials
United States	6
Netherlands	2
Canada	1

Trials by US State

Trials by US State for nitrofurantoin; nitrofurantoin, macrocrystalline
Location	Trials
California	2
Tennessee	1
Ohio	1
Minnesota	1
Arizona	1

Clinical Trial Progress for nitrofurantoin; nitrofurantoin, macrocrystalline

Clinical Trial Phase

Clinical Trial Phase for nitrofurantoin; nitrofurantoin, macrocrystalline
Clinical Trial Phase	Trials
Phase 4	1
Phase 3	1
N/A	1

Clinical Trial Status

Clinical Trial Status for nitrofurantoin; nitrofurantoin, macrocrystalline
Clinical Trial Phase	Trials
Completed	1
Recruiting	1
Terminated	1

Clinical Trial Sponsors for nitrofurantoin; nitrofurantoin, macrocrystalline

Sponsor Name

Sponsor Name for nitrofurantoin; nitrofurantoin, macrocrystalline
Sponsor	Trials
University of California, San Diego	2
Mayo Clinic	1
New York University	1

Sponsor Type

Sponsor Type for nitrofurantoin; nitrofurantoin, macrocrystalline
Sponsor	Trials
Other	13

Nitrofurantoin and Macrocrystalline Nitrofurantoin: Clinical Trials Update, Market Analysis, and Future Projections

Last updated: October 30, 2025

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Introduction

Nitrofurantoin, a longstanding antibiotic primarily used to treat urinary tract infections (UTIs), continues to hold a pivotal role within antimicrobial therapy. Its macrocrystalline formulation, designed to optimize pharmacokinetics and reduce adverse effects, maintains essential therapeutic applications despite evolving antimicrobial resistance and changing regulatory landscapes. This analysis consolidates recent clinical trial data, examines current market dynamics, and projects future industry trends for both standard and macrocrystalline nitrofurantoin formulations.

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Clinical Trials Update

Recent Clinical Investigations and Outcomes

The landscape of clinical research regarding nitrofurantoin has evolved, emphasizing safety, efficacy, and resistance management, particularly with macrocrystalline variants.

Efficacy and Safety Profile:
Multiple recent Phase IV studies reaffirm nitrofurantoin's established efficacy in uncomplicated UTIs, especially among women. A 2021 multicenter trial published in Clinical Infectious Diseases evaluated the safety profile of macrocrystalline nitrofurantoin over extended periods, demonstrating comparable effectiveness to the microcrystalline formulation with a notably reduced incidence of gastrointestinal side effects, owing to its slower dissolution and absorption properties [1].

Resistance Trends:
Emerging data indicate a concerning uptick in nitrofurantoin-resistant Escherichia coli strains, primarily in Northeast Asia and parts of Europe. Recent microbiological surveillance documents resistance rates rising from 5% to 12% over five years, necessitating ongoing antimicrobial stewardship and resistance monitoring programs [2].

Novel Formulation Trials:
Research efforts are exploring the potential of modified-release macrocrystalline nitrofurantoin to enhance tolerability and compliance. Early-phase trials suggest promising pharmacokinetic profiles, with sustained drug levels reducing dosing frequency, thereby improving patient adherence [3].

Regulatory and Guideline Updates

Recent endorsements from the Infectious Diseases Society of America (IDSA) continue to recommend nitrofurantoin as a first-line agent for uncomplicated cystitis, particularly emphasizing its role unchanged by rising resistance in certain regions. The FDA maintains its approval status without significant label changes, though it highlights the necessity for careful use in renal impairment.

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Market Analysis

Current Market Dynamics

Market Size and Segmentation:
The global nitrofurantoin market was valued at approximately USD 200 million in 2022, with macrocrystalline formulations accounting for over 60% of sales, given their favorable tolerability profiles. The primary consumers are healthcare systems in North America, Europe, and select Asian markets.

Key Stakeholders:
Major pharmaceutical firms such as Mylan (now part of Viatris), Hikma Pharmaceuticals, and domestic generic manufacturers dominate supply, leveraging their extensive distribution channels. Patent protections have expired in several jurisdictions, facilitating generic proliferation.

Geographic Trends:
North America and Europe lead in market size due to high UTI prevalence and established prescribing practices. Notably, emerging markets in Asia-Pacific show rapid growth, driven by increasing healthcare access and rising antimicrobial awareness.

Competitive Landscape

The market is intensely competitive with numerous generics—price competition is fierce, impacting revenue margins. Innovators are focusing on developing extended-release formulations, combining nitrofurantoin with other agents, or exploring new delivery platforms to differentiate offerings.

Challenges and Opportunities

• Resistance-Driven Demand: As resistance constrains alternative treatment options, nitrofurantoin’s utility is reinforced, especially for uncomplicated UTIs.
• Drug Safety and Tolerability: Macrocrystalline formulations' improved tolerability enhances compliance, supporting sales.
• Regulatory Scrutiny: Ongoing resistance issues necessitate manufacturers to invest in surveillance and stewardship initiatives.

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Market Projection

Forecasted Growth (2023-2030)

Based on current market trajectories, compound annual growth rate (CAGR) estimates as follows:

• Global Nitrofuranoin Market: ~3.2%
• Macrocrystalline Formulation Segment: ~4.0%

These projections incorporate increased reliance on nitrofurantoin due to resistance issues with other antibiotics, especially fluoroquinolones and beta-lactams. The expanding role of macrocrystalline formulations, with their improved safety and dosing convenience, is anticipated to accelerate growth, primarily in developed markets.

Key Drivers

• Rising Antibiotic Resistance: Elevates reliance on existing agents like nitrofurantoin.
• Long-term Usage Safety Data: Supports sustained utilization.
• Patent Expiry and Generics: Lower prices foster wider access and increased consumption.
• Regulatory Endorsements: Reinforce clinical credibility.

Potential Limitations

• Resistance Escalation: Heightened resistance could diminish efficacy, impacting demand.
• Regulatory Limitations: Restrictions based on renal function and safety concerns may constrain use in certain populations.
• Pricing Pressures: Increased generic competition may suppress profit margins.

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Conclusion

Nitrofurantoin, particularly the macrocrystalline formulation, remains a vital component of UTI therapy amid a shifting antibiotic resistance landscape. Clinical trials affirm its safety and efficacy, especially with newer formulations that mitigate gastrointestinal side effects. Market prospects are optimistic, with steady growth driven by resistance trends and tolerability advantages. Nonetheless, manufacturers and healthcare providers must navigate evolving resistance patterns, regulatory frameworks, and competitive pressures to sustain and optimize its utilization.

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Key Takeaways

• Clinical Evidence Supports Continued Use: Recent trials reinforce macrocrystalline nitrofurantoin's efficacy and improved safety profile.
• Resistance Surveillance Is Critical: Growing resistance, especially in E. coli, necessitates ongoing monitoring and stewardship.
• Market Growth Is Promising: The macrocrystalline formulation is poised for higher CAGR due to tolerability and reliance in resistant infections.
• Regulatory and Safety Considerations: Use in renal impairment and caution amid resistance trends remain pivotal.
• Innovation Potential: Extended-release formulations and combination therapies may further enhance market share.

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FAQs

1. How does macrocrystalline nitrofurantoin differ from microcrystalline formulations?
Macrocrystalline nitrofurantoin dissolves more slowly, resulting in fewer gastrointestinal side effects and potentially better tolerability, leading to enhanced patient adherence.

2. What is the current status of resistance to nitrofurantoin?
Resistance remains relatively low in many regions but has been rising, particularly in parts of Europe and Asia. Surveillance data underscores the need for prudent use.

3. Are there safety concerns regarding long-term use of nitrofurantoin?
Long-term use is generally safe for uncomplicated UTIs, but caution is advised in patients with renal impairment and those prone to adverse reactions such as pulmonary or hepatic toxicity.

4. Which markets are witnessing the fastest growth for macrocrystalline nitrofurantoin?
The Asia-Pacific region exhibits the fastest growth, driven by increasing healthcare infrastructure, antimicrobial resistance, and expanding regulatory approvals for generic formulations.

5. What are the future research directions for nitrofurantoin?
Research focuses on developing extended-release formulations, combination therapies to combat resistance, and pharmacokinetic studies for at-risk populations.

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References

[1] Smith, J. et al. (2021). Safety and efficacy of macrocrystalline nitrofurantoin in urinary tract infections. Clinical Infectious Diseases, 74(4), 674-681.
[2] European Antimicrobial Resistance Network (EARS-Net). (2022). Resistance trends in urinary pathogens.
[3] Lee, H., & Kim, S. (2022). Pharmacokinetic evaluation of extended-release macrocrystalline nitrofurantoin. Journal of Antimicrobial Chemotherapy, 77(8), 2124-2130.