CLINICAL TRIALS PROFILE FOR INSPRA

All Clinical Trials for Inspra

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00108251 ↗	Aldosterone Antagonism in Diastolic Heart Failure	Completed	US Department of Veterans Affairs	Phase 4	2004-08-01	The primary purpose of this study is to determine whether eplerenone has a beneficial effect on improving exercise ability in patients with diastolic heart failure.
NCT00108251 ↗	Aldosterone Antagonism in Diastolic Heart Failure	Completed	VA Office of Research and Development	Phase 4	2004-08-01	The primary purpose of this study is to determine whether eplerenone has a beneficial effect on improving exercise ability in patients with diastolic heart failure.
NCT00223717 ↗	Treatment of Supine Hypertension in Autonomic Failure	Completed	Vanderbilt University	Phase 1	2001-01-01	Supine hypertension is a common problem that affects at least 50% of patients with primary autonomic failure. Supine hypertension can be severe, and complicates the treatment of orthostatic hypotension. Drugs used for the treatment of orthostatic hypotension (eg, fludrocortisone and pressor agents), worsen supine hypertension. High blood pressure may also cause target organ damage in this group of patients. The pathophysiologic mechanisms causing supine hypertension in patients with autonomic failure have not been defined. In a study, we, the investigators at Vanderbilt University, examined 64 patients with AF, 29 with pure autonomic failure (PAF) and 35 with multiple system atrophy (MSA). 66% of patients had supine systolic (systolic blood pressure [SBP] > 150 mmHg) or diastolic (diastolic blood pressure [DBP] > 90 mmHg) hypertension (average blood pressure [BP]: 179 ± 5/89 ± 3 mmHg in 21 PAF and 175 ± 5/92 ± 3 mmHg in 21 MSA patients). Plasma norepinephrine (92 ± 15 pg/mL) and plasma renin activity (0.3 ± 0.05 ng/mL per hour) were very low in a subset of patients with AF and supine hypertension. (Shannon et al., 1997). Our group has showed that a residual sympathetic function contributes to supine hypertension in patients with severe autonomic failure and that this effect is more prominent in patients with MSA than in those with PAF (Shannon et al., 2000). MSA patients had a marked depressor response to low infusion rates of trimethaphan, a ganglionic blocker; the response in PAF patients was more variable. At 1 mg/min, trimethaphan decreased supine SBP by 67 +/- 8 and 12 +/- 6 mmHg in MSA and PAF patients, respectively (P < 0.0001). MSA patients with supine hypertension also had greater SBP response to oral yohimbine, a central alpha2 receptor blocker, than PAF patients. Plasma norepinephrine decreased in both groups, but heart rate did not change in either group. This result suggests that residual sympathetic activity drives supine hypertension in MSA; in contrast, supine hypertension in PAF. It is hoped that from this study will emerge a complete picture of the supine hypertension of autonomic failure. Understanding the mechanism of this paradoxical hypertension in the setting of profound loss of sympathetic function will improve our approach to the treatment of hypertension in autonomic failure, and it could also contribute to our understanding of hypertension in general.

Clinical Trial Conditions for Inspra

Condition Name

Condition Name for Inspra
Intervention	Trials
Hypertension	9
Metabolic Syndrome	3
Metabolic Syndrome X	2

Condition MeSH

Condition MeSH for Inspra
Intervention	Trials
Hypertension	7
Metabolic Syndrome	5
Heart Failure	4

Clinical Trial Locations for Inspra

Trials by Country

Trials by Country for Inspra
Location	Trials
United States	24
Canada	7
Netherlands	6
United Kingdom	4
France	4

Trials by US State

Trials by US State for Inspra
Location	Trials
Tennessee	5
Ohio	3
Massachusetts	2
Pennsylvania	2
Missouri	2

Clinical Trial Progress for Inspra

Clinical Trial Phase

Clinical Trial Phase for Inspra
Clinical Trial Phase	Trials
Phase 4	13
Phase 3	5
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for Inspra
Clinical Trial Phase	Trials
Completed	19
Terminated	6
Unknown status	3

Clinical Trial Sponsors for Inspra

Sponsor Name

Sponsor Name for Inspra
Sponsor	Trials
Vanderbilt University Medical Center	5
Pfizer	4
Brigham and Women's Hospital	3

Sponsor Type

Sponsor Type for Inspra
Sponsor	Trials
Other	48
Industry	10
U.S. Fed	3

Clinical Trials and Efficacy of INSPRA (Eplerenone)

Introduction to INSPRA

INSPRA, or eplerenone, is a steroid nucleus-based mineralocorticoid receptor (MR) antagonist, known for its higher selectivity compared to spironolactone. It is used in the treatment of various cardiovascular conditions, including heart failure and hypertension.

Key Clinical Trials

EMPHASIS-HF Trial

The EMPHASIS-HF trial was a landmark study that demonstrated the efficacy of INSPRA in patients with chronic heart failure with mild symptoms. This trial showed a statistically significant 37% relative risk reduction in cardiovascular (CV) mortality and heart failure hospitalization for patients treated with eplerenone compared to those given placebo, in addition to standard heart failure therapy[3].

• Early Stopping: Recruitment to the trial was halted early due to the significant difference in the primary endpoint favoring eplerenone.
• Endpoints: The trial significantly reduced rates of heart failure hospitalization, all-cause hospitalization, and all-cause mortality.

REMINDER Trial

The REMINDER trial evaluated the efficacy of INSPRA in patients with acute ST-segment elevation myocardial infarction (STEMI) without heart failure. The trial found statistically significant risk reductions in the primary composite efficacy endpoint, which included CV mortality, re-hospitalization, or extended initial hospital stay due to heart failure, among other criteria[4].

• Early Treatment: The trial supported the use of INSPRA within the first 24 hours of symptoms, preferably within the first 12 hours.
• Follow-Up: The mean follow-up time was 10.5 months, and the trial was conducted in 11 countries.

EPHESUS Trial

The EPHESUS trial focused on patients with heart failure post-myocardial infarction. This study showed that INSPRA reduced the overall incidence of adverse events such as hyperkalemia and increased creatinine levels, although these were still more frequent in the INSPRA group compared to the placebo group[1].

• Patient Demographics: The trial included 3307 patients treated with INSPRA and 3301 placebo-treated patients.
• Adverse Events: Discontinuations due to hyperkalemia or abnormal renal function were less than 1.0% in both groups.

Safety and Adverse Reactions

Hyperkalemia

One of the significant safety concerns with INSPRA is the risk of hyperkalemia. Patients treated with INSPRA, especially those with proteinuria, diabetes, or both, had higher rates of hyperkalemia compared to the placebo group[1].

• Monitoring: Serum potassium levels must be monitored before initiating INSPRA therapy, within the first week, and at one month after the start of treatment or dose adjustment.
• Renal Function: Serum creatinine levels should also be checked within 3–7 days of initiating a moderate CYP3A inhibitor, ACE inhibitors, angiotensin-II blockers, or non-steroidal anti-inflammatory drugs.

Other Adverse Reactions

Other adverse reactions identified during postapproval use include gynecomastia and abnormal vaginal bleeding, which were more common with increasing duration of therapy[1].

Market Analysis and Projections

Current Market Position

INSPRA has established itself as a valuable treatment option for cardiovascular conditions, particularly in the management of heart failure and hypertension. The drug's efficacy in reducing CV mortality and morbidity has been well-documented in clinical trials.

Market Trends

The pharmaceutical market, particularly for cardiovascular drugs, is influenced by several factors including regulatory approvals, competition, and patient needs.

• Regulatory Landscape: Decisions by regulatory authorities regarding labeling and additional indications can significantly impact the market position of INSPRA[3][4].
• Competition: The market for cardiovascular drugs is competitive, with other MR antagonists and cardiovascular treatments available. However, INSPRA's selectivity and efficacy profile make it a preferred choice in certain patient populations.

Future Projections

Given the strong clinical evidence supporting its use, INSPRA is likely to maintain its market presence and potentially expand into new indications.

• Emerging Risks and Opportunities: As the healthcare landscape evolves, there may be opportunities for INSPRA to address emerging cardiovascular risks and needs, particularly in the context of chronic heart failure and post-myocardial infarction care.
• Regulatory Approvals: Future regulatory approvals for additional indications could further enhance the drug's market position and expand its patient base.

Key Takeaways

• Clinical Efficacy: INSPRA has demonstrated significant reductions in CV mortality and morbidity in clinical trials.
• Safety Monitoring: Close monitoring of serum potassium and creatinine levels is crucial to manage the risk of hyperkalemia and renal dysfunction.
• Market Position: INSPRA remains a valuable treatment option in the cardiovascular drug market, with potential for expansion into new indications.
• Regulatory and Competitive Landscape: The drug's market trajectory will be influenced by regulatory decisions and competitive dynamics.

FAQs

Q: What is INSPRA used for? A: INSPRA (eplerenone) is used in the treatment of heart failure post-myocardial infarction and hypertension.

Q: What are the key findings of the EMPHASIS-HF trial? A: The EMPHASIS-HF trial showed a statistically significant 37% relative risk reduction in CV mortality and heart failure hospitalization for patients treated with eplerenone compared to placebo.

Q: What are the common adverse reactions associated with INSPRA? A: Common adverse reactions include hyperkalemia, increased creatinine levels, gynecomastia, and abnormal vaginal bleeding.

Q: Why is serum potassium monitoring important for patients on INSPRA? A: Serum potassium monitoring is crucial to manage the risk of hyperkalemia, which is a significant safety concern with INSPRA.

Q: What is the impact of INSPRA on renal function? A: INSPRA can increase creatinine levels, and patients, especially those with reduced creatinine clearance, need close monitoring of renal function.

Sources

1. Pfizer: Highlights of Prescribing Information - INSPRA.
2. Amwins: State of the Market - 2025 Outlook.
3. Pfizer: Adding INSPRA® (eplerenone) to Standard Therapy Significantly Reduces the Risk of CV Mortality and Morbidity in Patients With Chronic Heart Failure With Mild Symptoms, Study Shows.
4. Pfizer: New trial results support treatment with Inspra (eplerenone) within first 24 hours of symptoms, in addition to standard therapy, in patients with acute STEMI without heart failure.

Last updated: 2025-01-01