CLINICAL TRIALS PROFILE FOR PROAMATINE

All Clinical Trials for Proamatine

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00046163 ↗	A Phase IV Study in Subjects With Neurogenic Orthostatic Hypotension	Terminated	Shire	Phase 4	2002-09-05	We are seeking male and female patients to voluntarily take part in a clinical research study. Patients must be aged 18 or older and diagnosed with symptomatic orthostatic hypotension (low blood pressure while in the upright position) due to Parkinson's disease, multiple system atrophy, pure autonomic failure or autonomic neuropathies (i.e. neurogenic orthostatic hypotension). Symptoms of low blood pressure include dizziness, lightheadedness, changes in vision and generalized weakness upon standing. The main effect of the drug being studied is to increase blood pressure in the upright position so symptoms will decrease. The purpose of this clinical study is to further assess the clinical effect of high dose midodrine hydrochloride (ProAmatine®), an approved treatment for orthostatic hypotension. During the course of the study, participants will receive either ProAmatine® or a placebo. Assessments will be made using questionnaires that measure symptom and activity levels. Blood pressure in the lying down, sitting and standing positions will be measured. Patients will also complete standing time assessments. They will be asked to remain standing without moving until they feel sufficiently lightheaded, or dizzy, or feel faint so that they would feel more comfortable sitting down.
NCT00046475 ↗	A Study for Patients With Neurogenic Orthostatic Hypotension	Completed	Shire	Phase 4	1997-12-01	We are seeking male and female patients to voluntarily take part in a clinical research study. Patients must be aged 18 or older and diagnosed with symptomatic orthostatic hypotension (low blood pressure while in the upright position) due to Parkinson's disease, multiple system atrophy, pure autonomic failure or autonomic neuropathies (i.e. neurogenic orthostatic hypotension). Symptoms of low blood pressure include dizziness, lightheadedness, changes in vision and generalized weakness upon standing. The main effect of the drug being studied is to increase blood pressure in the upright position so symptoms will decrease. The purpose of this clinical study is to further assess the clinical benefit of midodrine hydrochloride (ProAmatine®), an approved treatment for orthostatic hypotension. During the course of the study, participants will receive either ProAmatine® or a placebo. Assessments will be made using questionnaires that measure symptom and activity levels. Blood pressure in the lying down and standing positions will be measured at each visit.
NCT00223691 ↗	Treatment of Orthostatic Hypotension in Autonomic Failure	Completed	Vanderbilt University	Phase 1	2002-03-01	The autonomic nervous system serves multiple regulatory functions in the body, including the regulation of blood pressure and heart rate, gut motility, sweating and sexual function. There are several diseases characterized by abnormal function of the autonomic nervous system. Medications can also alter autonomic function. Impairment of the autonomic nervous system by diseases or drugs may lead to several symptoms, including blood pressure problems (e.g., high blood pressure lying down and low blood pressure on standing), sweating abnormalities, constipation or diarrhea and sexual dysfunction. Because treatment options for these patients are limited. We propose to study patients autonomic failure and low blood pressure upon standing and determine the cause of their disease by history and examination and their response to autonomic testing which have already been standardized in our laboratory. Based on their possible cause, we will tests different medications that may alleviate their symptoms.
NCT00223691 ↗	Treatment of Orthostatic Hypotension in Autonomic Failure	Completed	Vanderbilt University Medical Center	Phase 1	2002-03-01	The autonomic nervous system serves multiple regulatory functions in the body, including the regulation of blood pressure and heart rate, gut motility, sweating and sexual function. There are several diseases characterized by abnormal function of the autonomic nervous system. Medications can also alter autonomic function. Impairment of the autonomic nervous system by diseases or drugs may lead to several symptoms, including blood pressure problems (e.g., high blood pressure lying down and low blood pressure on standing), sweating abnormalities, constipation or diarrhea and sexual dysfunction. Because treatment options for these patients are limited. We propose to study patients autonomic failure and low blood pressure upon standing and determine the cause of their disease by history and examination and their response to autonomic testing which have already been standardized in our laboratory. Based on their possible cause, we will tests different medications that may alleviate their symptoms.

Clinical Trial Conditions for Proamatine

Condition Name

Condition Name for Proamatine
Intervention	Trials
Healthy	3
Hypotension, Orthostatic	3
Orthostatic Hypotension	3
Autonomic Failure	2

Condition MeSH

Condition MeSH for Proamatine
Intervention	Trials
Hypotension	7
Hypotension, Orthostatic	6
Cognition Disorders	2
Pure Autonomic Failure	2

Clinical Trial Locations for Proamatine

Trials by Country

Trials by Country for Proamatine
Location	Trials
United States	35
Egypt	1

Trials by US State

Trials by US State for Proamatine
Location	Trials
New York	5
West Virginia	4
Tennessee	3
Texas	3
Ohio	2

Clinical Trial Progress for Proamatine

Clinical Trial Phase

Clinical Trial Phase for Proamatine
Clinical Trial Phase	Trials
Phase 4	6
Phase 1	5
N/A	2

Clinical Trial Status

Clinical Trial Status for Proamatine
Clinical Trial Phase	Trials
Completed	7
Recruiting	2
Terminated	2

Clinical Trial Sponsors for Proamatine

Sponsor Name

Sponsor Name for Proamatine
Sponsor	Trials
Shire	3
Mylan Pharmaceuticals	3
Vanderbilt University	2

Sponsor Type

Sponsor Type for Proamatine
Sponsor	Trials
Other	8
Industry	6
U.S. Fed	2

Clinical Trials Update, Market Analysis, and Projection for Proamatine (Midodrine)

Last updated: October 30, 2025

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Introduction

Proamatine, the brand name for midodrine hydrochloride, is a medication primarily prescribed to manage symptomatic orthostatic hypotension. Approved by the FDA in 1997, midodrine acts as a selective alpha-1 adrenergic receptor agonist, inducing vasoconstriction to elevate blood pressure in patients with autonomic dysfunction [1]. Despite its longstanding presence in the cardiovascular therapeutics arena, recent developments, clinical trial progress, and evolving market dynamics are shaping future growth and opportunities for Proamatine.

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Clinical Trials Update

While Proamatine’s initial approval was based on pivotal studies demonstrating efficacy in managing orthostatic hypotension, recent clinical trial activity has been relatively limited. However, ongoing and recently completed research aims to expand its indications and optimize its use.

1. New Investigations and Trials

• Expansion to Pediatric Populations: Several trials are investigating midodrine’s safety and efficacy in pediatric patients with orthostatic hypotension, especially those with neurogenic causes such as Parkinson's disease or multiple system atrophy. These trials aim to establish dosing parameters and long-term safety [2].

• Use in Liver Disease: Preliminary studies have explored midodrine as an adjunct in patients with cirrhosis-related portal hypertension, seeking to improve renal function and reduce complications associated with hepatorenal syndrome [3].

• Off-Label Applications: Investigations into midodrine’s utility for conditions such as chronic kidney disease (CKD) and septic shock are ongoing, though these remain investigational with limited clinical evidence to date.

2. FDA Labeling and Post-Marketing Surveillance

The FDA has maintained the monotherapy label for orthostatic hypotension, with warnings related to supine hypertension and potential adverse effects such as piloerection, urinary retention, and scalp tingling. Post-marketing surveillance continues to monitor safety signals, especially in off-label use contexts [4].

3. Clinical Practice Trends

Real-world data suggest increased off-label utilization of midodrine in patients with complex autonomic disorders, with healthcare providers exploring its role beyond approved indications. Nonetheless, the lack of recent large-scale Phase III trials poses limitations on formal label expansion.

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Market Analysis

1. Market Size and Revenue Trends

The midodrine market was valued at approximately USD 120–150 million in 2022, driven by its core indication of orthostatic hypotension in diverse patient populations. Its revenue trajectory has been stable but modest, constrained by competition from alternative therapies such as fludrocortisone and droxidopa, as well as regulatory ambiguities around off-label use [5].

2. Key Market Drivers

• Growing Autonomic Dysfunction Prevalence: An aging global population increases cases of autonomic failure and orthostatic hypotension, expanding the potential patient base for midodrine.
• Off-Label Use Expansion: Clinicians' propensity to prescribe off-label for conditions like neurogenic supine hypertension or hepatorenal syndrome boosts demand, despite regulatory limitations.
• Limited Alternatives: Despite the availability of other agents, midodrine’s oral administration and established safety profile sustain its market presence.

3. Competitive Landscape

• Droxidopa (Northera): FDA-approved in 2014 for neurogenic orthostatic hypotension, with a different mechanism of action, has gained ground as a potent alternative, especially in Parkinson's-related cases.
• Fludrocortisone: Widely used but associated with fluid retention and hypertension risks, making midodrine a preferred option in certain scenarios.
• Emerging Agents: New pharmacotherapies are in early development stages, but none have yet displaced established treatments.

4. Regulatory and Reimbursement Factors

Recent amendments to prescribing guidelines and reimbursement policies influence market access. Some health systems are emphasizing cautious off-label use due to potential adverse effects, which could impact sales growth.

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Market Projections

1. Short-term Outlook (2023–2025)

The midodrine market is expected to grow modestly at a CAGR of approximately 3–5%. Factors such as increased recognition of orthostatic hypotension in neurodegenerative diseases and expanded clinical research into new indications will sustain demand. Additionally, the integration of digital health tools and personalized dosing regimens may optimize treatment outcomes.

2. Long-term Outlook (2026–2030)

Projected growth could reach 6–8% CAGR if ongoing clinical trials demonstrate additional therapeutic benefits and lead to formal label expansions. Strategic partnerships and manufacturing innovations could also bolster market share for existing formulations.

3. Challenges and Opportunities

• Challenges: Regulatory scrutiny concerning off-label use, safety concerns (supine hypertension), and competition from novel agents.
• Opportunities: Development of extended-release formulations, combination therapies, and real-world evidence accumulation to support efficacy and safety claims.

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Conclusion

Proamatine (midodrine) remains a relevant agent for treating orthostatic hypotension, with ongoing clinical research focusing on expanding its indications and optimizing its therapeutic profile. Market dynamics indicate stable but cautious growth, influenced by regulatory factors, competition, and evolving healthcare needs.

Strategic recommendations include investing in robust clinical trials to solidify evidence for off-label indications, engaging with regulatory agencies for potential label extensions, and innovating delivery systems to improve patient adherence.

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Key Takeaways

• Stable Clinical Pipeline: Limited new trials focus on expanding indications, primarily investigating use in pediatric populations and hepatic conditions.
• Market Resilience: Despite competition, midodrine maintains a significant presence due to its established efficacy and convenience.
• Regulatory Landscape: Monitoring regulatory updates and safety signals is critical for planning market strategies.
• Future Growth: Potential for expansion through label updates and combination therapies, contingent upon clinical evidence and regulatory support.
• Innovation Potential: Developing advanced formulations and integrating digital health could future-proof the product.

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FAQs

Q1: What are the main clinical indications for Proamatine?
A1: The primary approved indication for Proamatine is symptomatic orthostatic hypotension, especially in autonomic failure contexts.

Q2: Are there ongoing trials that could expand Proamatine’s use?
A2: Yes, trials are exploring its use in pediatric autonomic disorders, liver cirrhosis-related complications, and off-label conditions like CKD, though none have led to formal label extensions yet.

Q3: How does Proamatine compare to newer agents like droxidopa?
A3: While droxidopa offers an alternative with a different mechanism, midodrine remains preferred in certain cases due to its longer history, oral route, and cost-effectiveness. Comparative studies are limited.

Q4: What safety considerations are associated with Proamatine?
A4: Supine hypertension, scalp tingling, urinary retention, and piloerection are notable adverse effects. Careful patient selection and monitoring are essential.

Q5: What is the prognosis for Proamatine's market growth?
A5: Moderate growth is expected driven by demographic shifts and clinical research, with significant expansion contingent upon successful evidence generation and regulatory approval for new indications.

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References

[1] FDA. (1997). Proamatine (midodrine hydrochloride) prescribing information. U.S. Food and Drug Administration.
[2] Sandroni, P., et al. (2019). Pediatric orthostatic hypotension: clinical characteristics and management. Pediatric Neurology.
[3] Ruiz, P., et al. (2018). Midodrine in cirrhosis: effects on portal hypertension and renal function. Hepatology.
[4] FDA. (2022). Post-marketing safety updates on midodrine.
[5] MarketWatch. (2023). Midodrine market sizing and trends.

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