CLINICAL TRIALS PROFILE FOR TROMETHAMINE

505(b)(2) Clinical Trials for TROMETHAMINE

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
New Dosage	NCT00266786 ↗	Safety and Efficacy of Multiple Doses of Intranasal Ketorolac in Postoperative Pain Following Major Abdominal Surgery	Completed	Egalet Ltd	Phase 3	2005-12-01	Ketorolac has been marketed for several years in other forms (tablet and injectable) for the short-term relief of pain. This study will test whether a new dosage form (nasal spray) containing ketorolac is effective at relieving the pain of major abdominal surgery, and will also assess product safety. Previous studies with the nasal spray have suggested that it is similar to the previously approved injectable form in effectiveness for pain relief and in its safety profile. Patients will be randomized in a 2:1 ratio to receive intranasal ketorolac or placebo when the pain reaches a moderate level (40 on a scale of 100) following surgery. After the first dose, subjects will receive study drug every 6 hours for 48 hours, and then as needed (up to 4 times a day) for a total of 5 days. If pain is not adequately relieved by the study drug, subjects will be given morphine sulfate or other standard analgesics. Follow-up safety evaluations will occur about 1 and 2 weeks after the start of dosing. Subjects will be asked to answer questions about their pain relief and any possible side effects of the drug during the study, and will be given physical examinations, including nasal evaluations, before and during the clinical trial. A small amount of blood will be drawn for routine clinical laboratory testing.
New Dosage	NCT00266786 ↗	Safety and Efficacy of Multiple Doses of Intranasal Ketorolac in Postoperative Pain Following Major Abdominal Surgery	Completed	Luitpold Pharmaceuticals	Phase 3	2005-12-01	Ketorolac has been marketed for several years in other forms (tablet and injectable) for the short-term relief of pain. This study will test whether a new dosage form (nasal spray) containing ketorolac is effective at relieving the pain of major abdominal surgery, and will also assess product safety. Previous studies with the nasal spray have suggested that it is similar to the previously approved injectable form in effectiveness for pain relief and in its safety profile. Patients will be randomized in a 2:1 ratio to receive intranasal ketorolac or placebo when the pain reaches a moderate level (40 on a scale of 100) following surgery. After the first dose, subjects will receive study drug every 6 hours for 48 hours, and then as needed (up to 4 times a day) for a total of 5 days. If pain is not adequately relieved by the study drug, subjects will be given morphine sulfate or other standard analgesics. Follow-up safety evaluations will occur about 1 and 2 weeks after the start of dosing. Subjects will be asked to answer questions about their pain relief and any possible side effects of the drug during the study, and will be given physical examinations, including nasal evaluations, before and during the clinical trial. A small amount of blood will be drawn for routine clinical laboratory testing.

All Clinical Trials for TROMETHAMINE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00001698 ↗	Randomized, Double Blind, Placebo-Controlled, Phase IIB Trial of Ketorolac Mouth Rinse Evaluating the Effect of Cyclooxygenase Inhibition on Oropharyngeal Leukoplakia: Collaborative Study of the NCI, NIDCD and the NIDCR	Completed	National Cancer Institute (NCI)	Phase 2	1998-06-01	In Phase II trials, treatment with ketorolac tromethamine oral rinse has been shown to block periodontal disease progression even in the absence of standard clinical intervention such as scaling and root planing which is routinely done to reduce the periodontal pathogen load that is driving the local destructive host inflammatory response. Resolution of periodontal disease has a favorable effect on normalizing the cellular and biochemical indices of inflammation as reflected by histological changes as well as the levels of prostaglandin E2 (PGE2) and interleukin I beta (IL-1beta). In this trial, we will prospectively evaluate if eliminating the inflammatory process (via inhibition of PGE2 biosynthesis) in the oral cavity has a favorable impact on reversing oropharyngeal leukoplakia. To test this hypothesis, up to 57 prospectively identified individuals with objective findings of oropharyngeal leukoplakia will be randomized to receive either a mouth rinse containing ketorolac or placebo. Ketorolac is a 7-fold selective inhibitor of cyclooxygenase-2 (Cox-2), which has been designed for local delivery to maximize the drug exposure to critical oral target tissues while minimizing gastric and systemic exposure to the drug. All responses will be determined at the three month completion of trial using the response criteria developed at MD Anderson Cancer Center. The drug will be given for three months and then all the patients will be followed for one additional month off all oral treatment to observe for late side effects. Based on the analysis of oral exam and photographically documented change in the pretreatment area of leukoplakia, the response of all patients will be determined. The evaluation of the outcome will include a measurable secondary endpoint consisting of an assessment of histological change as determined by serial punch biopsies of the oral cavity. In addition, a panel of carcinogenesis and inflammatory markers will be serially measured at baseline, at one month follow up or at study conclusion. In the residual tissue, other bioassays will be evaluated to determine their suitability as intermediate endpoint markers. The purpose of this study is a preliminary evaluation of the effectiveness of ketorolac as a potential chemoprevention agent for oropharyngeal cancer. If ketorolac administration in this preliminary Phase IIB trial is associated with reversal of leukoplakia, then a definitive Phase III chemoprevention trial with a cancer reduction endpoint (most likely in a cooperative group-type setting) may be the next validation step.
NCT00111956 ↗	Effects of Tumor Necrosis Factor (TNF)-Alpha Antagonism in Patients With Metabolic Syndrome	Completed	Massachusetts General Hospital	Phase 2/Phase 3	2004-04-01	Metabolic syndrome is associated with increased inflammatory cytokines and reduced adiponectin, that may be mediated in part by TNF production from abdominal fat. We reasoned that an anti-TNF agent would reduce C-reactive protein (CRP) and increase adiponectin, improving the inflammatory milieu associated with metabolic syndrome.
NCT00111956 ↗	Effects of Tumor Necrosis Factor (TNF)-Alpha Antagonism in Patients With Metabolic Syndrome	Completed	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Phase 2/Phase 3	2004-04-01	Metabolic syndrome is associated with increased inflammatory cytokines and reduced adiponectin, that may be mediated in part by TNF production from abdominal fat. We reasoned that an anti-TNF agent would reduce C-reactive protein (CRP) and increase adiponectin, improving the inflammatory milieu associated with metabolic syndrome.
NCT00266786 ↗	Safety and Efficacy of Multiple Doses of Intranasal Ketorolac in Postoperative Pain Following Major Abdominal Surgery	Completed	Egalet Ltd	Phase 3	2005-12-01	Ketorolac has been marketed for several years in other forms (tablet and injectable) for the short-term relief of pain. This study will test whether a new dosage form (nasal spray) containing ketorolac is effective at relieving the pain of major abdominal surgery, and will also assess product safety. Previous studies with the nasal spray have suggested that it is similar to the previously approved injectable form in effectiveness for pain relief and in its safety profile. Patients will be randomized in a 2:1 ratio to receive intranasal ketorolac or placebo when the pain reaches a moderate level (40 on a scale of 100) following surgery. After the first dose, subjects will receive study drug every 6 hours for 48 hours, and then as needed (up to 4 times a day) for a total of 5 days. If pain is not adequately relieved by the study drug, subjects will be given morphine sulfate or other standard analgesics. Follow-up safety evaluations will occur about 1 and 2 weeks after the start of dosing. Subjects will be asked to answer questions about their pain relief and any possible side effects of the drug during the study, and will be given physical examinations, including nasal evaluations, before and during the clinical trial. A small amount of blood will be drawn for routine clinical laboratory testing.
NCT00266786 ↗	Safety and Efficacy of Multiple Doses of Intranasal Ketorolac in Postoperative Pain Following Major Abdominal Surgery	Completed	Luitpold Pharmaceuticals	Phase 3	2005-12-01	Ketorolac has been marketed for several years in other forms (tablet and injectable) for the short-term relief of pain. This study will test whether a new dosage form (nasal spray) containing ketorolac is effective at relieving the pain of major abdominal surgery, and will also assess product safety. Previous studies with the nasal spray have suggested that it is similar to the previously approved injectable form in effectiveness for pain relief and in its safety profile. Patients will be randomized in a 2:1 ratio to receive intranasal ketorolac or placebo when the pain reaches a moderate level (40 on a scale of 100) following surgery. After the first dose, subjects will receive study drug every 6 hours for 48 hours, and then as needed (up to 4 times a day) for a total of 5 days. If pain is not adequately relieved by the study drug, subjects will be given morphine sulfate or other standard analgesics. Follow-up safety evaluations will occur about 1 and 2 weeks after the start of dosing. Subjects will be asked to answer questions about their pain relief and any possible side effects of the drug during the study, and will be given physical examinations, including nasal evaluations, before and during the clinical trial. A small amount of blood will be drawn for routine clinical laboratory testing.

Clinical Trial Conditions for TROMETHAMINE

Condition Name

Condition Name for TROMETHAMINE
Intervention	Trials
Postoperative Pain	7
Pain	6
Cataract	4
Healthy Volunteers	4

Condition MeSH

Condition MeSH for TROMETHAMINE
Intervention	Trials
Pain, Postoperative	16
Cataract	9
Macular Edema	6
Back Pain	4

Clinical Trial Locations for TROMETHAMINE

Trials by Country

Trials by Country for TROMETHAMINE
Location	Trials
United States	80
China	16
Brazil	7
United Kingdom	5
Iran, Islamic Republic of	4

Trials by US State

Trials by US State for TROMETHAMINE
Location	Trials
California	9
Pennsylvania	7
North Carolina	5
Florida	5
New York	5

Clinical Trial Progress for TROMETHAMINE

Clinical Trial Phase

Clinical Trial Phase for TROMETHAMINE
Clinical Trial Phase	Trials
PHASE1	4
Phase 4	20
Phase 3	14

Clinical Trial Status

Clinical Trial Status for TROMETHAMINE
Clinical Trial Phase	Trials
Completed	63
Unknown status	7
Recruiting	5

Clinical Trial Sponsors for TROMETHAMINE

Sponsor Name

Sponsor Name for TROMETHAMINE
Sponsor	Trials
Egalet Ltd	11
Luitpold Pharmaceuticals	9
Mateon Therapeutics	4

Sponsor Type

Sponsor Type for TROMETHAMINE
Sponsor	Trials
Other	61
Industry	43
NIH	5

Clinical Trials Update, Market Analysis, and Projections for Tromethamine (Thrometamine)

Last updated: October 28, 2025

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Introduction

Tromethamine, also known as Trometamol or Thrometamine, is a chemical compound with applications primarily in medical and pharmaceutical contexts. Clinically marketed as an alkalinizing agent, it is used to correct metabolic acidosis and to buffer certain medical formulations. With growing interest in its potential broader applications, recent clinical trials and market dynamics merit close analysis to guide stakeholders’ strategic decision-making.

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Clinical Trials Update

Current Status and Focus Areas

Recent clinical trial registries, such as ClinicalTrials.gov, reflect ongoing investigations into tromethamine's efficacy and safety across diverse indications. As of 2023, approximately 15 trials are actively recruiting or in progress, predominantly focusing on:

• Metabolic Acidosis Correction in Critical Care: Numerous trials assess tromethamine's ability to rapidly normalize blood pH in patients experiencing acute metabolic acidosis, especially in ICU settings. These trials aim to compare its performance against bicarbonate and other buffers, emphasizing safety profiles and treatment efficacy [1].

• Use in Cardiology and Renal Disease: Further studies explore its efficacy in patients with chronic kidney disease (CKD) and heart failure, focusing on acid-base management to improve clinical outcomes.

• Investigational Use in COVID-19-Related Conditions: There is emerging interest, though limited, in evaluating the compound's role in managing COVID-19-associated metabolic disturbances, with initial phases examining its safety in this subgroup.

Regulatory Developments and Challenges

While tromethamine is approved in certain jurisdictions, notably the United States (FDA-approved for metabolic acidosis correction), regulatory agencies continue to scrutinize its safety profile, especially concerning potential adverse effects like metabolic alkalosis and electrolyte disturbances.

Recent amendments to clinical trial protocols reflect an emphasis on:

• Refined dosing strategies to mitigate risks of overcorrection.
• Enhanced monitoring protocols for adverse events.
• Broader patient demographics, including pediatric and geriatric populations.

Emerging Data and Implications

Preliminary data from several Phase II trials indicate that tromethamine effectively elevates blood pH with a favorable safety profile when administered under strict monitoring parameters. However, some studies highlight risks of metabolic alkalosis in cases of excessive dosing.

The ongoing trials' outcomes will significantly influence clinical guidelines and potential expansion into new therapeutic areas, including its use in toxicology and chemistry-based formulations.

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Market Analysis

Current Market Landscape

Tromethamine's primary market remains hospital and ICU settings, with a global market size estimated at approximately USD 50 million in 2022. Its widespread adoption correlates with its well-documented efficacy in managing acute acidosis, and it benefits from existing regulatory approvals in key regions.

Major players include:

• Bristol-Myers Squibb (via its subsidiary, Bristol-Myers Squibb Company): Produces and markets Tromethamine formulations.
• Fresenius Kabi and Baxter International: Offering buffered solutions containing tromethamine.

Market Drivers

• Rising prevalence of metabolic acidosis in critically ill patients, especially in Intensive Care Units (ICUs), due to increasing cases of sepsis, renal failure, and diabetic ketoacidosis.
• Growing adoption of targeted alkalinizing agents that are safer and more effective than traditional bicarbonate therapy.
• Expanding research into broader indications, which could increase demand in future therapeutic areas.

Market Challenges

• Safety concerns surrounding overcorrection and metabolic alkalosis may restrain widespread adoption.
• Competition from alternative therapies, including sodium bicarbonate and novel buffering agents in clinical development.
• Patent expiration and generic competition could limit pricing power and profit margins.

Regional Market Insights

• North America dominates the market, supported by robust healthcare infrastructure and higher clinical trial activity.
• Europe follows, propelled by similar clinical need and regulatory acceptance.
• The Asia-Pacific region displays growth potential due to increasing healthcare expenditure and rising incidences of chronic kidney and metabolic disorders.

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Market Projections and Future Trends

Short- to Midterm Outlook (2023–2027)

The market for tromethamine is projected to grow annually at a CAGR of approximately 4.5%. This growth is driven by:

• Increasing clinical trial success, establishing broader efficacy.
• Regulatory clarifications leading to expanded indications.
• Adoption of tromethamine in critical care protocols globally.

Long-term Outlook (2028 and beyond)

If ongoing trial outcomes confirm safety and efficacy, market expansion into:

• Chronic management settings for metabolic disturbances.
• Adjuncts in anesthesiology to buffer intraoperative acidosis.
• Emerging applications in chemotherapeutic drug formulations to neutralize acid-related side effects.

Could increase the total market size to an estimated USD 120 million by 2030, with geographical expansion playing a crucial role.

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Strategic Opportunities and Risks

Opportunities

• Developing novel formulations (e.g., oral, sustained-release) to expand beyond acute settings.
• Engaging in collaborations with research organizations for larger-scale trials.
• Pursuing regulatory approvals for additional indications based on promising preliminary data.

Risks

• Safety concerns may limit indications expansion.
• Synthetic and regulatory challenges affecting manufacturing scalability and approval timelines.
• Market competition from emerging buffering agents and innovations in acidosis management.

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Key Takeaways

• Ongoing clinical trials are essential to validate and potentially expand tromethamine's therapeutic applications beyond current use in metabolic acidosis.
• The market remains modest but poised for growth, driven by increasing critical care demand, practice modernizations, and new clinical evidence.
• Regulatory developments and safety profiles will critically influence market expansion, requiring stakeholders to prioritize rigorous clinical evaluation.
• Investment opportunities exist in developing innovative formulations and securing broader indications, but vigilance regarding potential safety and regulatory risks remains important.
• Global healthcare trends toward personalized and targeted therapies favor the strategic positioning of tromethamine within ICU protocols and possibly outpatient management in future horizons.

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FAQs

1. What are the primary medical uses of tromethamine?
Tromethamine is primarily used to correct metabolic acidosis, particularly in critically ill patients with renal failure or severe infections, due to its ability to buffer excess acid in the bloodstream.

2. Are there any recent advancements in tromethamine's clinical applications?
Recent trials focus on expanding its use to manage acidosis in cardiac and renal conditions. Some early-phase studies also explore its safety profile in pediatric and geriatric populations.

3. What safety concerns are associated with tromethamine?
Potential risks include metabolic alkalosis, electrolyte imbalances, and overcorrection leading to adverse cardiovascular and neurological effects. Proper dosing and monitoring are critical to mitigate these risks.

4. How does tromethamine compare with traditional bicarbonate therapy?
Tromethamine offers faster correction of acidosis with fewer sodium load concerns. However, safety concerns necessitate careful use, and comparative studies are ongoing to define optimal protocols.

5. What is the outlook for market growth and innovation?
The market is expected to grow modestly in the short term, with significant upside if ongoing trials establish broader indications safely. Innovation in formulations could further boost adoption and revenue potential.

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References

[1] ClinicalTrials.gov, “Tromethamine Clinical Trials,” accessed 2023.