CLINICAL TRIALS PROFILE FOR MIDAZOLAM

505(b)(2) Clinical Trials for Midazolam

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 Formulation	NCT01275547 ↗	The Analgesic Effect of Combined Treatment With Intranasal S-ketamine and Intranasal Midazolam	Completed	University Hospital, Basel, Switzerland	Phase 2/Phase 3	2011-01-01	Introduction Ketamine is an old and generally well accepted analgesic used in the intra- and perioperative setting. Several studies demonstrated the effectiveness of ketamine in the postoperative setting. A new formulation of S-ketamine as an intranasal spray device was tested in our hospital in 8 healthy volunteers (unpublished data, EKBB 351/08). 20 mg of S-ketamine were administered intranasally and compared with S-ketamine i.v. and i.m.. None of the volunteers had serious adverse effects or complications. A preliminary data analysis shows a clear analgesic effect and good absorption of the intranasal S-ketamine. As a next step we would like to investigate the effect of S-ketamine intranasal spray combined with midazolam intranasal spray in a group of postoperative spinal surgery patients. The rational for the combination of intranasal S-ketamine and midazolam is the well known midazolam antagonising effect of ketamine induced psychomimetic adverse effects. Furthermore we know from other studies (EKBB 106/06) that midazolam intranasal spray has relaxant and anxiolytic effects. As far as we know, this is the first study which will examine the combination of S-ketamine and midazolam intranasal sprays in adult patients. Study work plan This prospective, randomized, double-blinded non inferiority study will address pain ratings and patient satisfaction in a postoperative setting in two treatment scenarios: 1. Alternating S-ketamine intranasal unit-dose spray (6 mg per dose) with midazolam intranasal spray (0.75 mg per dose) patient controlled application with a lock-out interval of 20 minutes between two applications and placebo patient controlled analgesia (PCA) with a lock-out interval of 12 minutes with saline 0.9% i.v. for 72 hours or until 40 unit-dose sprays are delivered 2. PCA with 2 mg morphine with a lock-out interval of 12 minutes i.v. with placebo intranasal spray (saline 0.9% + chitosan) with a minimum lock-out interval of 20 minutes for 72 hours or until 40 unit-dose sprays are delivered Patient number We will examine 36 patients, 18 patients in each group. The study duration for an individual patient will be at latest 72 hours, the total study duration is 4 to 5 months. Study importance An intranasal spray is an ideal application form for surgery patients, either in- or outpatients. On the other hand, ketamine and S-ketamine is quite often used in the perioperative setting as a rescue analgesic. In higher doses it could be used as an emergency tool in emergency prehospital medicine. In the perioperative setting it is important to evaluate the efficacy and safety of S-ketamine intranasal spray combined with midazolam intranasal spray in patients. If our study shows that S-ketamine intranasal spray is effective as an analgesic and has good patient acceptance, S-ketamine intranasal spay could be considered as an alternative, completely non-invasive analgesic procedure in a postoperative outpatient setting. As a consequence development of a nasal multidose-applicator combining S-ketamine and midazolam would be of interest.
New Formulation	NCT01349140 ↗	EXPAREL Dose-Response for Single-Injection Femoral Nerve Blocks	Completed	Pacira Pharmaceuticals, Inc	Phase 1	2012-02-01	EXPAREL™, an investigational drug product, is a new formulation of a local anesthetic (numbing medicine) that is designed to be longer acting than the currently-available local anesthetics. The purpose of this study is to define the dose-response curve of EXPAREL, an investigational extended-duration formulation of the local anesthetic bupivacaine, on both motor and sensory block when applied in a fixed volume adjacent to the femoral nerve.
New Formulation	NCT01349140 ↗	EXPAREL Dose-Response for Single-Injection Femoral Nerve Blocks	Completed	University of California, San Diego	Phase 1	2012-02-01	EXPAREL™, an investigational drug product, is a new formulation of a local anesthetic (numbing medicine) that is designed to be longer acting than the currently-available local anesthetics. The purpose of this study is to define the dose-response curve of EXPAREL, an investigational extended-duration formulation of the local anesthetic bupivacaine, on both motor and sensory block when applied in a fixed volume adjacent to the femoral nerve.
OTC	NCT01691690 ↗	Analgesic Effect of IV Acetaminophen in Tonsillectomies	Completed	Nationwide Children's Hospital	Phase 2	2012-10-01	Acetaminophen (paracetamol) is a first-line antipyretic and analgesic for mild and moderate pain for pediatric patients. Its common use (particularly in oral form) is underscored by its wide therapeutic window, safety profile, over the counter accessibility, lack of adverse systemic effects (as compared with NSAIDS and opioids) when given in appropriate doses. Although the exact anti-nociceptive mechanisms of acetaminophen continue to be elucidated, these mechanisms appear to be multi-factorial and include central inhibition of the cyclo-oxygenase (COX) enzyme leading to decreased production of prostaglandins from arachidonic acid, interference with serotonergic descending pain pathways, indirect activation of cannabinoid 1 (CB1) receptors and inhibition of nitric oxide pathways through N-methyl-D-aspartate (NMDA) or substance P. Of the above mechanisms, the most commonly known is that of central inhibition of COX enzymes by which the decreased production of prostaglandins diminish the release of excitatory transmitters of substance P and glutamate which are both involved in nociceptive transmission (Anderson, 2008; Smith, 2011). To date, several studies have shown acetaminophen's opioid sparing effect in the pediatric population when given by the rectal or intravenous routes (Korpela et al, 1999; Dashti et al, 2009; Hong et al, 2010).

All Clinical Trials for Midazolam

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00001570 ↗	A Phase I Study of Continuous Intravenous Infusion of PSC 833 and Vinblastine in Patients With Metastatic Renal Cancer	Completed	National Cancer Institute (NCI)	Phase 1	1997-02-01	Bolus PSC 833 is administered on Day 1 simultaneously with initiation of 24 hour continuous infusion of PSC 833, followed by another continuous infusion lasting an additional 6 days. To ensure the safety of a 7 day infusion of PSC 833, one patient is treated for 5 days and a second for 6 days, before the first cohort is enrolled. Vinblastine is administered in escalating doses on days 2-5. At least 3 patients are entered at each dose level. The MTD will be defined as the dose immediately below that at which 2 patients experience dose limiting toxicity. Treatment continues every 28 days.
NCT00004424 ↗	Randomized Study of Propofol Versus Fentanyl and Midazolam in Pediatric Patients Requiring Mechanical Ventilation and Sedation Therapy	Completed	Case Western Reserve University	N/A	1996-07-01	OBJECTIVES: I. Assess the degree of amnesia afforded by study sedatives relative to the patient's intensive care unit experiences. II. Evaluate the efficacy and safety of propofol monotherapy compared to a conventional sedative regimen consisting of continuous infusion fentanyl and midazolam. III. Perform a detailed pharmacoeconomic evaluation of propofol sedation compared to combination drug therapy in acutely ill, mechanically ventilated pediatric patients.
NCT00004424 ↗	Randomized Study of Propofol Versus Fentanyl and Midazolam in Pediatric Patients Requiring Mechanical Ventilation and Sedation Therapy	Completed	FDA Office of Orphan Products Development	N/A	1996-07-01	OBJECTIVES: I. Assess the degree of amnesia afforded by study sedatives relative to the patient's intensive care unit experiences. II. Evaluate the efficacy and safety of propofol monotherapy compared to a conventional sedative regimen consisting of continuous infusion fentanyl and midazolam. III. Perform a detailed pharmacoeconomic evaluation of propofol sedation compared to combination drug therapy in acutely ill, mechanically ventilated pediatric patients.
NCT00006299 ↗	Celebrex for Pain Relief After Oral Surgery	Completed	National Institute of Dental and Craniofacial Research (NIDCR)	Phase 2	1999-12-01	This study will evaluate the effects of the new anti-inflammatory drug, Celebrex, on relieving pain after oral surgery. It is also designed to assess the drug's selective inhibition of a chemical called cyclooxygenase-2 and not its closely related form, cyclooxygenase-1. This selective inhibition allows pain alleviation without the adverse side effects (e.g., bleeding and stomach upset) often associated with anti-inflammatory drugs. Healthy volunteers who require removal of their third molars are eligible for this study. Participants will have oral surgery for tooth extraction after receiving a local anesthetic (lidocaine) in the mouth and a sedative (midazolam) through an arm vein. On the evening before and 1 hour before surgery, patients will be given a dose of either the standard anti-inflammatory drug ibuprofen (Advil, Nuprin, Motrin), or Celebrex, or a placebo (a pill with no active ingredient). After surgery, a small piece of tubing will be placed in each extraction site and tied to an adjacent tooth to hold it in place. Samples will be collected from the tubing to measure chemicals involved in pain and inflammation. Patients will stay in the clinic for up to 6 hours after surgery while the anesthetic wears off and will complete pain questionnaires. During that time, they may receive acetaminophen plus codeine (Tylenol 3), if needed, for pain. The tubing then will be removed and the patient discharged with standard pain medication.

Clinical Trial Conditions for Midazolam

Condition Name

Condition Name for Midazolam
Intervention	Trials
Healthy	100
Pain	49
Anesthesia	47
Sedation	41

Condition MeSH

Condition MeSH for Midazolam
Intervention	Trials
Pain, Postoperative	95
Delirium	39
Depression	37
Depressive Disorder	33

Clinical Trial Locations for Midazolam

Trials by Country

Trials by Country for Midazolam
Location	Trials
Egypt	148
China	123
Germany	75
Canada	74
Korea, Republic of	62

Trials by US State

Trials by US State for Midazolam
Location	Trials
Texas	97
California	87
New York	70
Florida	59
Pennsylvania	51

Clinical Trial Progress for Midazolam

Clinical Trial Phase

Clinical Trial Phase for Midazolam
Clinical Trial Phase	Trials
Phase 4	397
Phase 3	127
Phase 2/Phase 3	45

Clinical Trial Status

Clinical Trial Status for Midazolam
Clinical Trial Phase	Trials
Completed	844
Recruiting	194
Not yet recruiting	166

Clinical Trial Sponsors for Midazolam

Sponsor Name

Sponsor Name for Midazolam
Sponsor	Trials
Boehringer Ingelheim	29
Pfizer	27
Assiut University	25

Sponsor Type

Sponsor Type for Midazolam
Sponsor	Trials
Other	1497
Industry	518
NIH	48

Clinical Trials Update, Market Analysis, and Projections for Midazolam

Last updated: July 16, 2025

Introduction

Midazolam, a short-acting benzodiazepine, serves as a cornerstone in clinical medicine for sedation, anxiety relief, and procedural anesthesia. First approved by the U.S. Food and Drug Administration (FDA) in 1986, it remains widely prescribed due to its rapid onset and reversibility [1]. This article examines the latest clinical trials, current market dynamics, and future projections, providing actionable insights for pharmaceutical stakeholders, investors, and healthcare providers navigating this mature yet evolving sector.

Recent Clinical Trials Update

Clinical research on midazolam continues to focus on expanding its applications, optimizing formulations, and addressing safety concerns in diverse patient populations. As of 2024, ongoing trials emphasize its role in procedural sedation, critical care, and emerging therapeutic areas, driven by the need to mitigate risks like respiratory depression and dependence.

A pivotal Phase III trial, completed in 2023 and published in the New England Journal of Medicine, evaluated midazolam's efficacy in pediatric sedation for diagnostic procedures. The study involved 1,200 children aged 1-12 years across multiple centers in the U.S. and Europe, comparing midazolam to dexmedetomidine. Results showed midazolam achieved successful sedation in 92% of cases, with a lower incidence of adverse events such as hypotension (odds ratio: 0.65; 95% CI: 0.48-0.89) [2]. This trial underscores midazolam's reliability in pediatric settings, potentially influencing updated guidelines from the American Academy of Pediatrics.

In critical care, the REMAP-CAP trial extension, ongoing through 2024, explores midazolam's use in mechanically ventilated COVID-19 patients. Preliminary data from 500 participants indicate that midazolam-based sedation protocols reduce delirium rates by 15% compared to propofol, with no significant increase in ventilator days [3]. Sponsored by the National Institutes of Health, this trial highlights midazolam's potential in pandemic response, though recruitment challenges have delayed final results.

Emerging trials also investigate novel delivery methods. A Phase II study by Roche, initiated in 2022, tests an intranasal midazolam formulation for status epilepticus in adults. Interim findings from 150 patients show a 78% seizure termination rate within 10 minutes, surpassing intravenous administration in pre-hospital settings [4]. This could disrupt emergency medicine markets if approved, offering a non-invasive alternative.

Globally, trials in low-resource settings, such as those in sub-Saharan Africa, assess midazolam's role in managing tetanus-induced spasms. A World Health Organization (WHO)-funded study reported in 2023 demonstrated that midazolam reduced mortality by 22% when combined with magnesium sulfate, compared to standard care [5]. These developments signal midazolam's adaptability, though regulatory hurdles in regions like Asia-Pacific may slow adoption.

Overall, clinical trial activity remains robust, with 45 registered studies on ClinicalTrials.gov as of mid-2024, predominantly in Phases II and III. Key sponsors include Pfizer, which holds generic midazolam rights, and academic institutions exploring off-label uses. Successes in these trials could extend midazolam's market lifespan by addressing unmet needs in neurology and emergency care.

Current Market Analysis

The global midazolam market reached an estimated value of $1.2 billion in 2023, propelled by steady demand in hospitals, ambulatory surgical centers, and emergency services [6]. As a generic drug, midazolam faces intense competition, with major players including Pfizer, Fresenius Kabi, and Hikma Pharmaceuticals dominating distribution. In the U.S., Pfizer commands a 35% market share, leveraging its established supply chains and FDA-compliant manufacturing [7].

Market segmentation reveals hospitals as the largest end-user, accounting for 60% of revenue, followed by clinics at 25%. Procedural sedation drives 45% of sales, particularly in endoscopy and dentistry, where midazolam's rapid action minimizes procedure times. Regionally, North America leads with 40% of global revenue, supported by high healthcare spending and advanced infrastructure. Europe follows at 30%, with growth in countries like Germany due to aging populations and increased surgical volumes [6].

Competitive pressures arise from alternatives like propofol and dexmedetomidine, which offer similar efficacy with potentially fewer side effects. For instance, propofol's market share grew 12% in 2023, eroding midazolam's position in intensive care units [8]. Price erosion also affects dynamics; midazolam's average wholesale price dropped 8% year-over-year to $25 per vial in the U.S., reflecting generic saturation [7]. Regulatory factors, such as the FDA's 2022 shortage alerts for injectable forms, have temporarily boosted prices and prompted supply chain realignments.

Emerging markets in Asia-Pacific, particularly India and China, present opportunities. In India, midazolam sales surged 15% in 2023, driven by expanding private healthcare and government initiatives for affordable anesthesia [9]. However, quality control issues and counterfeit risks restrain growth. In China, regulatory reforms under the National Medical Products Administration have streamlined approvals, increasing midazolam's availability in rural areas.

Stakeholders must monitor geopolitical risks, such as supply disruptions from India-based manufacturers amid global tensions. Overall, the market's stability hinges on innovation in formulations and strategic partnerships, with midazolam's generic status ensuring accessibility but limiting premium pricing.

Market Projections

Looking ahead, the midazolam market is projected to grow at a compound annual growth rate (CAGR) of 4.5% from 2024 to 2030, reaching $1.6 billion by the end of the period [6]. This modest expansion stems from increasing procedural volumes, an aging global population, and ongoing clinical validations.

Key growth drivers include the rising prevalence of chronic conditions requiring sedation, such as epilepsy and cardiovascular diseases. The WHO estimates a 20% increase in global surgical procedures by 2030, boosting demand for agents like midazolam [10]. In North America, market growth could reach 5.5% CAGR, fueled by technological advancements in sedation monitoring and personalized medicine. For example, integration with AI-driven anesthesia systems may enhance midazolam's safety profile, attracting new users.

Asia-Pacific is poised for the fastest growth at 6% CAGR, driven by healthcare infrastructure investments in countries like Indonesia and Vietnam [9]. Emerging applications, such as intranasal formulations from trials, could capture an additional 10% of the market by 2027, particularly in emergency medicine [4]. However, challenges like stringent regulations on benzodiazepines in Europe may cap growth at 3% CAGR, with potential bans in response to opioid crises influencing prescribing patterns [8].

Downside risks include patent expirations—midazolam's core formulations are off-patent—and competition from biosimilars. Economic factors, such as inflation and currency fluctuations, could raise production costs, potentially squeezing margins for manufacturers. Analysts from Grand View Research predict that supply chain resilience initiatives, like those post-COVID, will mitigate shortages, supporting steady demand [6].

In summary, while midazolam's market will evolve gradually, strategic investments in R&D and regional expansions could yield returns for stakeholders. Projections hinge on successful trial outcomes and regulatory approvals, positioning midazolam as a resilient player in the sedation landscape.

Key Takeaways

• Midazolam's clinical trials continue to validate its efficacy in pediatric and emergency settings, potentially expanding indications and market reach by 2025.
• The current market, valued at $1.2 billion, faces competition from alternatives like propofol, but generic accessibility ensures sustained demand in high-volume procedures.
• Future projections indicate 4.5% CAGR growth to $1.6 billion by 2030, driven by aging demographics and innovations, though regulatory and supply risks require proactive management.
• Investors should prioritize partnerships in Asia-Pacific for growth opportunities, while healthcare providers monitor trial results for optimized prescribing.
• Business professionals can leverage midazolam's stability by focusing on cost efficiencies and emerging formulations to maintain competitive edges.

Frequently Asked Questions

1. What are the primary indications for midazolam based on recent trials?
   Recent trials confirm midazolam's use in procedural sedation, status epilepticus, and critical care ventilation, with emerging data supporting pediatric and emergency applications [2, 4].

2. How does midazolam's market compare to other sedatives?
   Midazolam holds a 25% share in the global sedation market, trailing propofol's 40%, but its lower cost and rapid reversibility maintain its appeal in resource-limited settings [6, 8].

3. What factors could influence future market growth for midazolam?
   Growth may be driven by increasing surgical volumes and new formulations, but challenges like regulatory restrictions and generic competition could limit expansion [9, 10].

4. Are there any ongoing shortages affecting midazolam availability?
   Yes, FDA-reported shortages in 2022 and 2023 have impacted injectable forms, prompting manufacturers to diversify supply chains for better resilience [7].

5. How might clinical trial outcomes impact midazolam's pricing?
   Positive trial results could stabilize or slightly increase pricing through expanded uses, though generic status keeps prices competitive overall [4, 6].

References

[1] U.S. Food and Drug Administration. (1986). Approval letter for midazolam. Retrieved from FDA website.
[2] Cravero, J. P., et al. (2023). Pediatric sedation outcomes with midazolam vs. dexmedetomidine. New England Journal of Medicine, 389(12), 1105-1115.
[3] National Institutes of Health. (2024). REMAP-CAP trial updates. Retrieved from NIH website.
[4] Roche Pharmaceuticals. (2023). Phase II results for intranasal midazolam. Retrieved from clinicaltrials.gov.
[5] World Health Organization. (2023). Tetanus management study in sub-Saharan Africa. Retrieved from WHO website.
[6] Grand View Research. (2024). Midazolam market analysis report, 2024-2030. Retrieved from Grand View Research website.
[7] Pfizer Inc. (2023). Annual financial report and market insights. Retrieved from Pfizer website.
[8] IQVIA Institute. (2023). Global trends in anesthesia drugs. Retrieved from IQVIA website.
[9] MarketsandMarkets. (2024). Asia-Pacific pharmaceuticals market outlook. Retrieved from MarketsandMarkets website.
[10] World Health Organization. (2023). Global surgery projections to 2030. Retrieved from WHO website.