CLINICAL TRIALS PROFILE FOR ETHACRYNIC ACID

All Clinical Trials for ethacrynic acid

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01628731 ↗	Furosemide Versus Ethacrynic Acid in Children With Congenital Heart Disease	Completed	Bambino Gesù Hospital and Research Institute	Phase 3	2012-10-01	This study aims to verify if ethacrynic acid continuous infusion is superior to furosemide continuous infusion in total urine output production during the first 24 post operative hours.
NCT02017197 ↗	Therapeutic Equivalence Between Branded and Generic WARFArin Tablets in Brazil	Completed	Fundação de Amparo à Pesquisa do Estado de São Paulo	Phase 4	2014-08-01	The purpose of this study is to assess whether the switch from branded to generic warfarin or between different generic warfarin tablets may cause fluctuation in the results of coagulation tests (International Normalized Rate, acronym INR) in patients, thus predisposing them to unnecessary risks.
NCT02017197 ↗	Therapeutic Equivalence Between Branded and Generic WARFArin Tablets in Brazil	Completed	Federal University of São Paulo	Phase 4	2014-08-01	The purpose of this study is to assess whether the switch from branded to generic warfarin or between different generic warfarin tablets may cause fluctuation in the results of coagulation tests (International Normalized Rate, acronym INR) in patients, thus predisposing them to unnecessary risks.
NCT02852564 ↗	Ethacrynic Acid Elimination in Non-Muscle Invasive Bladder Cancer Patients Undergoing Transurethral Resection	Completed	University of Kansas Medical Center	Phase 1	2016-08-01	Phase 1 study to provide quantitative characterization of the renal elimination of ethacrynic acid and metabolites in patients with non-muscle invasive bladder cancer (NMIBC) at the time of transurethral resection of bladder tumor
NCT02852564 ↗	Ethacrynic Acid Elimination in Non-Muscle Invasive Bladder Cancer Patients Undergoing Transurethral Resection	Completed	Eugene Lee, MD	Phase 1	2016-08-01	Phase 1 study to provide quantitative characterization of the renal elimination of ethacrynic acid and metabolites in patients with non-muscle invasive bladder cancer (NMIBC) at the time of transurethral resection of bladder tumor
NCT04176328 ↗	Open-label, Dose-escalation Study to Evaluate the Pharmacokinetics of Inhaled Teicoplanin in Cystic Fibrosis Patients	Completed	Aptuit Srl	Phase 1	2019-10-25	Cystic Fibrosis (CF) is the most common autosomal recessive lethal disorders affecting 1:2.500 newborns among Caucasians. CF patients are peculiarly susceptible to infection and colonization of the respiratory tract with pathogens. In particular, Methicillin-resistant Staphylococcus aureus (MRSA) has become the third most prevalent bacterium in CF in the U.S. and has been increasing in other countries. Apart from the difficulty of treating the infection because of its antimicrobial resistances, MRSA is transmissible between individuals with and without CF. Chronic MRSA infection is associated with worse outcomes, and treatment/eradication is challenging. Antibiotic dosing and choices should be optimized to minimize further resistance and to maximize chances of successful therapy. Yet, MRSA has several mechanisms to escape clearance by the immune system and antibiotic killing. For these reasons, a better understanding of preventive measures and early therapy is of key importance. In consideration of all these assessments there is an emerging consensus that MRSA is an important pathogen in CF rather than simply a marker of severe disease. However, to date there are no guidelines or recommendations on the choice of antibiotics for MRSA in CF. Glycopeptides are an important class of antibiotics active against Gram-positive pathogens. These include teicoplanin and vancomycin, which are currently in widespread use and are active against MRSA. Teicoplanin is often preferred to vancomycin for intravenous treatment because of its better safety profile but its use in MRSA lung infection is limited by its limited lung penetration. Teicoplanin is mainly used for injection/infusion. Inhalation of anti-microbial drugs is a cornerstone in the treatment of patients with CF, since inhaled antibiotics decrease the rate of decline of lung function, improve the quality of life, and reduce the frequency of exacerbations and hospital admissions. It is expected that, using inhalation route, efficacy would be improved and risk of resistance reduced. At present, no antibiotic active against MRSA is available as an inhaled formulation. The objective of this phase I, first-in-man clinical study is to identify the dose providing, after single inhalation administration, a sputum Teicoplanin concentrations exceeding the drug concentration required to inhibit bacterial growth for at least 8 hours, while minimizing the development of resistance.
NCT04176328 ↗	Open-label, Dose-escalation Study to Evaluate the Pharmacokinetics of Inhaled Teicoplanin in Cystic Fibrosis Patients	Completed	Centro Ricerche Cliniche di Verona	Phase 1	2019-10-25	Cystic Fibrosis (CF) is the most common autosomal recessive lethal disorders affecting 1:2.500 newborns among Caucasians. CF patients are peculiarly susceptible to infection and colonization of the respiratory tract with pathogens. In particular, Methicillin-resistant Staphylococcus aureus (MRSA) has become the third most prevalent bacterium in CF in the U.S. and has been increasing in other countries. Apart from the difficulty of treating the infection because of its antimicrobial resistances, MRSA is transmissible between individuals with and without CF. Chronic MRSA infection is associated with worse outcomes, and treatment/eradication is challenging. Antibiotic dosing and choices should be optimized to minimize further resistance and to maximize chances of successful therapy. Yet, MRSA has several mechanisms to escape clearance by the immune system and antibiotic killing. For these reasons, a better understanding of preventive measures and early therapy is of key importance. In consideration of all these assessments there is an emerging consensus that MRSA is an important pathogen in CF rather than simply a marker of severe disease. However, to date there are no guidelines or recommendations on the choice of antibiotics for MRSA in CF. Glycopeptides are an important class of antibiotics active against Gram-positive pathogens. These include teicoplanin and vancomycin, which are currently in widespread use and are active against MRSA. Teicoplanin is often preferred to vancomycin for intravenous treatment because of its better safety profile but its use in MRSA lung infection is limited by its limited lung penetration. Teicoplanin is mainly used for injection/infusion. Inhalation of anti-microbial drugs is a cornerstone in the treatment of patients with CF, since inhaled antibiotics decrease the rate of decline of lung function, improve the quality of life, and reduce the frequency of exacerbations and hospital admissions. It is expected that, using inhalation route, efficacy would be improved and risk of resistance reduced. At present, no antibiotic active against MRSA is available as an inhaled formulation. The objective of this phase I, first-in-man clinical study is to identify the dose providing, after single inhalation administration, a sputum Teicoplanin concentrations exceeding the drug concentration required to inhibit bacterial growth for at least 8 hours, while minimizing the development of resistance.

Clinical Trial Conditions for ethacrynic acid

Condition Name

Condition Name for ethacrynic acid
Intervention	Trials
Fluid Overload	1
Atrial Fibrillation	1
Bladder Cancer	1
Cystic Fibrosis	1

Condition MeSH

Condition MeSH for ethacrynic acid
Intervention	Trials
Atrial Fibrillation	1
Fibrosis	1
Cystic Fibrosis	1
Urinary Bladder Neoplasms	1

Clinical Trial Locations for ethacrynic acid

Trials by Country

Trials by Country for ethacrynic acid
Location	Trials
Italy	2
United States	1
Brazil	1

Trials by US State

Trials by US State for ethacrynic acid
Location	Trials
Kansas	1

Clinical Trial Progress for ethacrynic acid

Clinical Trial Phase

Clinical Trial Phase for ethacrynic acid
Clinical Trial Phase	Trials
Phase 4	1
Phase 3	1
Phase 1	2

Clinical Trial Status

Clinical Trial Status for ethacrynic acid
Clinical Trial Phase	Trials
Completed	4

Clinical Trial Sponsors for ethacrynic acid

Sponsor Name

Sponsor Name for ethacrynic acid
Sponsor	Trials
University of Kansas Medical Center	2
Bambino Gesù Hospital and Research Institute	1
Fundação de Amparo à Pesquisa do Estado de São Paulo	1

Sponsor Type

Sponsor Type for ethacrynic acid
Sponsor	Trials
Other	8
Industry	3

Ethacrynic Acid Clinical Trials, Market Analysis, Patent Status and Forecast

Last updated: August 1, 2026

Ethacrynic acid is an established, off-patent loop diuretic with limited clinical-trial activity and a small, price-sensitive market. The drug remains clinically relevant for patients who require potent diuresis and have a documented sulfonamide allergy, although its ototoxicity and narrower commercial availability limit use versus furosemide and bumetanide. No active branded innovation program, meaningful patent barrier, or biosimilar issue materially protects the product’s market.

What is the current clinical status of ethacrynic acid?

Ethacrynic acid is an FDA-approved loop diuretic for treating edema associated with congestive heart failure, hepatic disease, renal disease, and other conditions requiring rapid fluid removal. It is available primarily as oral tablets and injectable sodium ethacrynate. The drug is marketed under the Edecrin name and through generic products. [1][2]

Attribute	Status
Active ingredient	Ethacrynic acid
Drug class	Loop diuretic
Primary mechanism	Inhibition of the Na-K-2Cl cotransporter in the thick ascending limb
Original U.S. approval	1960s
Main indications	Edema associated with cardiac, hepatic, and renal disease
FDA pathway	Conventional small-molecule drug approval
Common dosage forms	Oral tablets; injectable sodium ethacrynate
Reference brand	Edecrin
Biosimilar pathway	Not applicable
Patent-based exclusivity	Expired
Current development profile	Mature, low-innovation generic medicine

Ethacrynic acid has no sulfonamide group. Clinicians sometimes select it for patients with serious sulfonamide hypersensitivity, although cross-reactivity between sulfonamide antibiotics and non-antibiotic sulfonamides is generally considered limited and must be assessed clinically. [3]

The principal safety constraints are ototoxicity, electrolyte depletion, hypotension, dehydration, and acute kidney injury. Ototoxicity risk increases with rapid intravenous administration, high doses, severe renal impairment, and concurrent use of other ototoxic agents. [1]

Are there active clinical trials for ethacrynic acid?

Ethacrynic acid has no established late-stage clinical development program. Public trial activity is limited compared with newer diuretics, renal therapies, heart-failure therapies, and oncology agents.

Most current clinical use is based on historical approval, clinical experience, observational evidence, and guideline-driven treatment of volume overload rather than on a new registration-enabling trial program. Studies involving ethacrynic acid are more likely to evaluate:

• Diuresis in patients with heart failure or renal dysfunction.
• Management of fluid overload in intensive-care settings.
• Use in patients with suspected sulfonamide allergy.
• Ototoxicity and electrolyte safety.
• Experimental drug-repurposing concepts.

The drug is not a major investigational candidate for a new primary indication. Its mature safety profile and availability as an approved product reduce the commercial incentive to conduct large randomized trials.

How does ethacrynic acid compare with furosemide in clinical development?

Factor	Ethacrynic acid	Furosemide
Market position	Niche alternative	Dominant generic loop diuretic
Sulfonamide structure	No	Yes
Broad clinical evidence	Smaller	Extensive
Generic availability	Yes, but fewer suppliers	Broad
Ototoxicity concern	Significant	Significant, especially at high exposure
Typical commercial use	Selected patients	First-line loop-diuretic use
Active innovation	Minimal	Minimal as a molecule, but greater formulation activity
Trial density	Low	Higher because of broader use

Ethacrynic acid’s main clinical differentiator is the absence of a sulfonamide moiety, not superior efficacy. Furosemide generally has greater prescribing familiarity, broader supply, and lower acquisition cost. [1][4]

What is the FDA and Orange Book status of ethacrynic acid?

Ethacrynic acid is an approved small-molecule drug. The FDA-approved labeling identifies oral Edecrin tablets and injectable sodium ethacrynate for treatment of edema. [1]

The original product’s regulatory exclusivity has expired. Current commercial products are generic or legacy branded products rather than newly protected medicines.

What is the Orange Book listing status?

The Orange Book is relevant to approved ethacrynic acid products that have submitted drug applications, but the drug does not have a commercially meaningful period of unexpired patent exclusivity. Any listed patents associated with legacy products would not create a substantial barrier to generic entry if they are expired or otherwise unenforceable.

The commercial risk is therefore driven by:

• Abbreviated New Drug Application approval.
• Product availability.
• Manufacturing capacity.
• Injectable supply continuity.
• Hospital formulary decisions.
• Pricing and wholesaler contracts.

A generic applicant would ordinarily rely on an ANDA with a paragraph III certification where all relevant listed patents are expired, or a paragraph IV certification if an unexpired listing were identified and challenged. For this mature product, paragraph IV litigation is not the central market risk.

What patents protect ethacrynic acid?

No active composition-of-matter patent is expected to protect ethacrynic acid in the United States. The original discovery and product patents date from the mid-20th century and have expired.

Patent category	Current relevance
Ethacrynic acid composition patent	Expired
Original oral formulation patents	Expired
Original injectable formulation patents	Expired
Method-of-use patents for edema	Expired or commercially immaterial
Salt or ester protection	No known material barrier to standard generic use
New delivery-system protection	No major market-recognized estate
Manufacturing patents	Potentially relevant to a specific process, but not a barrier to the active ingredient itself

Are there formulation patents for ethacrynic acid?

No widely recognized active formulation patent estate materially protects standard ethacrynic acid tablets or injectable sodium ethacrynate. A company could seek patents for a new formulation, controlled-release system, combination product, or administration technology, but no such platform has established a significant commercial position.

Are there method-of-use patents for ethacrynic acid?

Historical methods of treating edema, fluid overload, and related conditions are generally too old to create meaningful exclusivity. A new patent could theoretically cover a narrowly defined use or dosing protocol, but a method-of-use patent would need to survive novelty, obviousness, written-description, enablement, and clinical-support challenges.

When does ethacrynic acid lose exclusivity?

Ethacrynic acid lost meaningful U.S. market exclusivity decades ago. The original product is not protected by a current composition patent or regulatory exclusivity period.

Exclusivity type	Status
New chemical entity exclusivity	Expired
Orphan-drug exclusivity	None identified
Pediatric exclusivity	None identified
U.S. composition patent	Expired
U.S. formulation patent	No material active barrier identified
Method-of-use exclusivity	No material current barrier identified
Biosimilar exclusivity	Not applicable

A generic entrant would not face the entry delay associated with an unexpired NCE, orphan, or pediatric exclusivity period.

What is the competitive landscape for ethacrynic acid?

The relevant competitive set is the loop-diuretic market rather than a dedicated ethacrynic acid market.

Drug	Competitive position
Furosemide	Standard low-cost comparator; broad oral and injectable use
Bumetanide	Potent alternative with predictable oral absorption
Torsemide	Longer-acting oral option, used heavily in chronic heart failure
Ethacrynic acid	Sulfonamide-free niche option
Combination diuretics	Used where sequential nephron blockade is needed

Furosemide is the primary competitive threat because it is inexpensive, familiar, and available in multiple strengths and routes. Bumetanide and torsemide compete in patients requiring more predictable oral exposure or different duration of action.

Ethacrynic acid retains a defensible clinical niche in patients for whom a sulfonamide-containing loop diuretic is unsuitable. That niche is limited by the drug’s adverse-effect profile and inconsistent availability.

What is the market size and revenue outlook for ethacrynic acid?

Ethacrynic acid is a low-revenue mature generic rather than a high-growth pharmaceutical asset. Public company filings generally do not report ethacrynic acid revenue separately, and market-research estimates vary because of different definitions of the market, geographic coverage, and inclusion of hospital injectable sales.

What drives ethacrynic acid demand?

Demand depends on several factors:

1. The number of patients with severe edema or fluid overload.
2. Prescriber preference for furosemide or bumetanide.
3. Documented sulfonamide allergy or avoidance.
4. Hospital purchasing and injectable supply.
5. Generic pricing.
6. Availability of oral tablets and injectable sodium ethacrynate.
7. Safety concerns involving ototoxicity and electrolyte abnormalities.

The product’s volume demand is likely stable to modestly declining in routine diuretic use. Revenue can rise temporarily during shortages of competing loop diuretics or when a hospital system adds ethacrynic acid to its formulary. Long-term revenue growth is unlikely without a new formulation, a new indication, or a supply disruption affecting competing products.

Ethacrynic acid market projection

A practical forecast uses scenario analysis rather than a single market-size estimate because product-specific public revenue data are limited.

Period	Base-case outlook	Main assumption
Near term	Flat to low-single-digit decline	Stable niche demand, generic price pressure
Medium term	Flat volume, declining value	Continued competition from furosemide and bumetanide
Upside case	Low-single-digit growth	Shortages, expanded hospital use, or new delivery technology
Downside case	Mid-single-digit decline or greater	Supplier exit, formulary substitution, or injectable discontinuation

The most probable commercial outcome is a small, stable niche with declining unit economics. An investor should treat ethacrynic acid as a supply-and-contracting opportunity, not as a conventional growth asset.

Which companies are challenging or manufacturing ethacrynic acid?

The commercial field includes legacy brand ownership, generic manufacturers, contract manufacturers, and hospital-supply distributors. Manufacturer participation can change because generic products are frequently discontinued, transferred, or placed on intermittent supply.

The key competitive variables are:

• FDA-approved product availability.
• National Drug Code continuity.
• Tablet and injectable manufacturing capacity.
• DEA and controlled-substance status, which is not a primary issue for ethacrynic acid.
• Hospital purchasing agreements.
• Ability to maintain quality and supply during low-volume production.

No major public patent dispute or paragraph IV campaign is associated with ethacrynic acid’s current commercial position. Litigation risk is more likely to involve product liability, manufacturing quality, labeling, shortage-related contracting, or antitrust questions than patent infringement.

What generic launch scenarios exist for ethacrynic acid?

Scenario 1: Standard tablet entry

A generic manufacturer enters with conventional tablets after demonstrating pharmaceutical equivalence and bioequivalence. The likely outcome is rapid price competition and limited differentiation.

Scenario 2: Injectable supply expansion

A manufacturer increases sodium ethacrynate injectable capacity. This could produce temporary pricing power if existing suppliers have shortages or discontinue production.

Scenario 3: Reformulated product

A company develops a lower-ototoxicity formulation, modified-release tablet, or hospital-ready injectable presentation. This would require clinical, regulatory, manufacturing, and patent investment. Commercial success would depend on proving a meaningful benefit over low-cost generic alternatives.

Scenario 4: Specialty allergy positioning

A manufacturer markets ethacrynic acid to hospitals and specialists treating patients with sulfonamide allergy concerns. The opportunity is clinically credible but limited by the size of the eligible population and by uncertainty over how often clinicians consider non-antibiotic sulfonamide cross-reactivity clinically significant.

What manufacturing and intellectual-property barriers exist?

The active ingredient is old and chemically established, so composition-of-matter IP is not the main barrier. Manufacturing barriers are more important.

Active pharmaceutical ingredient

Ethacrynic acid requires controlled synthesis, impurity management, analytical characterization, and reliable supply of pharmaceutical-grade raw materials. A low-volume market can discourage multiple API suppliers, increasing vulnerability to production interruptions.

Oral tablets

The main barriers are scale economics, stability, dissolution performance, packaging, and maintaining FDA-compliant manufacturing for a relatively small market.

Injectable sodium ethacrynate

Injectable production is more difficult because it requires sterile manufacturing, validated aseptic processing, container-closure integrity, stability data, and regulatory compliance. The injectable product has greater potential for supply scarcity than the tablet product.

IP barriers

A new entrant could face process patents or formulation patents owned by a specific developer, but no widely recognized active estate currently blocks conventional generic ethacrynic acid products.

What litigation and settlement agreements affect ethacrynic acid?

No major current patent litigation or high-profile paragraph IV settlement is associated with the mature ethacrynic acid market in the principal U.S. public records used for generic-drug analysis.

The absence of litigation reflects the product’s age and limited commercial value. A potential entrant would still need to review:

• FDA Orange Book listings.
• ANDA patent certifications.
• Product-specific patent assignments.
• Federal district court filings.
• Patent Trial and Appeal Board records.
• FDA shortage and discontinuation notices.

What is the geographic coverage of ethacrynic acid?

Ethacrynic acid is most commercially relevant in the United States and selected international markets where the product or equivalent formulations remain approved. Regulatory status varies by country, particularly for injectable sodium ethacrynate.

Region	Commercial assessment
United States	Established approval; generic and legacy-brand market
European Union	Country-specific availability; not uniformly commercialized
Canada	Availability depends on national product registrations and suppliers
Asia-Pacific	Variable approval and hospital use
Emerging markets	More likely to rely on other loop diuretics because of cost and supply

International expansion would require country-specific registration, local pharmacovigilance, supply-chain support, and pricing approval. The limited market size reduces the attractiveness of broad geographic investment unless a manufacturer already has a hospital-generic portfolio.

How strong is the patent estate for ethacrynic acid?

The patent estate is weak for exclusivity purposes.

Strength factor	Assessment
Composition patent	Very weak; expired
Formulation protection	Weak
Method-of-use protection	Weak
Manufacturing know-how	Moderate operational value
Regulatory exclusivity	None of commercial significance
Biosimilar protection	Not applicable
Litigation leverage	Low
Repositioning opportunity	Possible but unproven

Commercial defensibility depends on manufacturing reliability, hospital contracts, product availability, and regulatory execution rather than patent rights.

Key Takeaways

• Ethacrynic acid is an FDA-approved, off-patent loop diuretic with a small specialty market.
• Its principal clinical distinction is the absence of a sulfonamide group.
• Furosemide, bumetanide, and torsemide are the main commercial competitors.
• No meaningful current composition, formulation, or method-of-use patent barrier protects conventional products.
• No major paragraph IV campaign, patent litigation matter, or settlement agreement drives the market.
• Clinical-trial activity is limited and does not support a large new-indication development thesis.
• Injectable supply, not intellectual property, is the more significant commercial barrier.
• Base-case revenue is flat to declining because of generic price pressure and substitution by other loop diuretics.
• Upside depends on shortages, hospital formulary expansion, or a differentiated formulation.
• Biosimilar risk is irrelevant because ethacrynic acid is a chemically synthesized small molecule.

Frequently Asked Questions

Is ethacrynic acid still FDA approved?

Yes. FDA-approved labeling covers oral ethacrynic acid and injectable sodium ethacrynate for edema associated with cardiac, hepatic, renal, and related conditions. [1]

Is ethacrynic acid stronger than furosemide?

Ethacrynic acid is a potent loop diuretic, but it is not generally preferred over furosemide for routine use. Selection depends on dose, renal function, route, prior response, allergy history, and safety considerations.

Does ethacrynic acid have a biosimilar competitor?

No. Biosimilars apply to biological products. Ethacrynic acid is a synthetic small-molecule drug, so competition occurs through generic drug applications.

Can a new company patent ethacrynic acid?

A company cannot obtain a new composition patent on the old active ingredient merely by identifying it again. Patent protection could be possible for a genuinely novel formulation, manufacturing process, combination, or narrowly defined clinical use that satisfies patentability requirements.

Is ethacrynic acid commercially attractive for generic manufacturers?

It is more attractive as a niche hospital product or shortage-resilience product than as a high-volume generic. The injectable presentation may offer greater strategic value than tablets, but sterile-manufacturing costs and limited demand constrain returns.

References

1. U.S. Food and Drug Administration. (2023). EDECRIN (ethacrynic acid) tablets and sodium ethacrynate injection prescribing information. FDA/DailyMed labeling.

2. National Library of Medicine. (2024). DailyMed: Ethacrynic acid and sodium ethacrynate drug labeling. U.S. National Library of Medicine.

3. Wulf, N. R., & Matuszewski, K. A. (2013). Sulfonamide cross-reactivity: Is there evidence to support broad cross-allergenicity? American Journal of Health-System Pharmacy, 70(17), 1483-1494.

4. Ellison, D. H., & Felker, G. M. (2017). Diuretic treatment in heart failure. New England Journal of Medicine, 377(20), 1964-1975.