CLINICAL TRIALS PROFILE FOR MIDAZOLAM HYDROCHLORIDE PRESERVATIVE FREE

All Clinical Trials for MIDAZOLAM HYDROCHLORIDE PRESERVATIVE FREE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01055236 ↗	Hydroxyzine for the Prevention of Pruritus From Spinal Morphine in Transabdominal Hysterectomy Patients	Completed	Mahidol University	Phase 4	2007-08-01	Hydroxyzine is one of antihistamines that antagonizes H1 receptor, and it's effects are reducing pruritus, nausea/vomiting, and the mild effect of sedation.With these effects Hydroxyzine should be used in the prevention of these symptoms.
NCT01236859 ↗	Gabapentin for Prophylaxis Intrathecal Morphine-Induced Pruritus	Completed	Prince of Songkla University	N/A	2009-09-01	Intrathecal morphine provides good postoperative analgesia for up to 18-24 hour after administration. Pruritus is the most common side effect of intrathecal morphine, which the incidence was reported as 20%-100%2 and 63% in Songklanagarind Hospital. Pathophysiology of opioid-induced pruritus remain unclear and more than one mechanism may be involved in the development of opioid-induced pruritus, such as, mediated central µ opioid receptors, Dopamine (D2) receptors, Serotonin (5-HT3) receptors, prostaglandin system, GABA receptors, and glycine receptors, so that why opioid-induced pruritus is difficult to manage. Many medications have been used to treat this side effect included antihistamines, 5-HT3 (serotonin) receptor antagonists, opioid antagonists, opioid agonist-antagonists, propofol, and nonsteroidal antiinflammatory drugs. Gabapentin is an anticonvulsant, a structural analog of aminobutyric acid, and currently approved by the Food and Drug Administration for the treatment of partial seizures and postherpetic neuralgia. Many studies have shown gabapentin to be effective in the case of brachioradial pruritus, itch of neuropathic in origin, uremic pruritus, multiple sclerosis-induced pruritus,cholestatic pruritus, itch produced by burn, and pruritus of unknown origin. However, there is only one small study in Taiwan shown the effectiveness of gabapentin 1200 mg in prevention of intrathecal morphine-induced pruritus in orthopedic surgery, which could reduce incidence of pruritus from 77.5% to 47.5% (38.7% reduction). Because gabapentin has several side effects especially in high dose such as drowsiness, dry mouth, headache, unsteadiness, reduced co-ordination or slowed reaction, constipation, diarrhea, peripheral edema, dizziness, confusion, loss of concentration, weight gain, and nausea, vomiting, so in our study we decided to reduce the dose of gabapentin. Therefore, we would like to know if gabapentin in a smaller dose (600 mg) used in the wider range of age including the elderly can decrease the incidence of intrathecal morphine-induced pruritus in orthopedic surgery in Songklanagarind Hospital.
NCT01404442 ↗	Evaluation of the Analgesic Effect of Midazolam and Ketamine as an Additive to Intrathecal Bupivacaine in Patients Undergoing Cesarean Section	Completed	Qazvin University Of Medical Sciences	Phase 1/Phase 2	2011-05-01	Objective :To compare the analgesic effect of intrathecal midazolam and ketamine as an additive to bupivacaine in patients undergoing cesarean section . Methods:Following Ethics Committee approval and informed patients consent, Ninety patients 18-45 yr old ASA physical status I or II, scheduled for cesarean section under spinal anesthesia, were studied in a prospective, double-blinded, randomized way. The patients were randomly allocated to one of three groups of 30 each. The ketamine group (groupK) received bupivacaine 10mg combined with 0.1 mg/kg ketamine preservative free ,the midazolam group (group M) received bupivacaine 10mg combined with0.02 mg/ kg midazolam and the placebo group (group P) received bupivacaine 10mg combined with 0.5ml distilled water intrathecally . Time to first requirement of analgesic supplement, Sensory block onset time, maximum sensory level , onset of motor block, duration of blockade, hemodynamics variables, the incidence of hypotension, ephedrine requirements, bradycardia ,hypoxemia [Saturation of peripheral oxygen (SpO2)4) if time of administration of diclofenac Na less than 8h,Pethidine 25 mg IV was given.
NCT01971645 ↗	Decadron as Adjuvant in Femoral Nerve Blocks in Knee Arthroscopy	Completed	Nationwide Children's Hospital	Phase 3	2014-07-01	If preservative-free dexamethasone 0.1 mg/kg (max dose 4 mg) is added to ropivacaine 0.5% 2 mg/kg (max dose 100 mg), then post-PACU opioid consumption will be reduced by 33%.
NCT02825056 ↗	Postoperative Hemodynamics Comparison After High Spinal Block With or Without Intrathecal Morphine.	Unknown status	Postgraduate Institute of Medical Education and Research	Early Phase 1	2016-07-01	There is paucity of literature on the effects of intrathecal morphine on the postoperative hemodynamics in the cardiac-surgical patients.We planned this study to compare the post-operative hemodynamic effects (particularly the incidence of vasoplegia in the two study groups) and outcome of combined general anesthesia + high spinal block, with or without intrathecal morphine in patients undergoing cardiac-surgical procedures in our set up.
NCT02882633 ↗	Lumbar Plexus Block vs Fascia Iliaca Block After Hip Arthroscopy	Completed	University of Pennsylvania	N/A	2015-11-01	The purpose of this study is to compare lumbar plexus block to fascia iliac block done in adult patients who have undergone hip arthroscopy surgery. Visual analogue scores, opioid consumption, and quality of recovery 48 hours post operatively will be used for comparison.
NCT03035942 ↗	Quality of Recovery After Dexamethasone, Ondansetron or Placebo Intrathecal Morphine Administration	Completed	Pontificia Universidade Catolica de Sao Paulo	Phase 4	2017-01-02	The aim of this study is to evaluate not only the occurrence of side effects, but the quality of the recovery (QoR-40 Questionnaire) of patients submitted to spinal anesthesia with administration of low doses (0.1 mg) of intrathecal morphine for the surgical treatment of fractures in one of the lower limbs and who will receive prophylactic ondansetron (4mg), dexamethasone (8mg) or placebo.

Clinical Trial Conditions for MIDAZOLAM HYDROCHLORIDE PRESERVATIVE FREE

Condition Name

Condition Name for MIDAZOLAM HYDROCHLORIDE PRESERVATIVE FREE
Intervention	Trials
Pruritus	3
Postperfusion Syndrome	1
Analgesia	1
Morphine Adverse Reaction	1

Condition MeSH

Condition MeSH for MIDAZOLAM HYDROCHLORIDE PRESERVATIVE FREE
Intervention	Trials
Pruritus	3
Nausea	2
Pain, Postoperative	2
Vomiting	2

Clinical Trial Locations for MIDAZOLAM HYDROCHLORIDE PRESERVATIVE FREE

Trials by Country

Trials by Country for MIDAZOLAM HYDROCHLORIDE PRESERVATIVE FREE
Location	Trials
United States	15
Egypt	3
Thailand	2
Brazil	1
Saudi Arabia	1

Trials by US State

Trials by US State for MIDAZOLAM HYDROCHLORIDE PRESERVATIVE FREE
Location	Trials
Pennsylvania	2
Ohio	2
Virginia	2
Texas	1
North Carolina	1

Clinical Trial Progress for MIDAZOLAM HYDROCHLORIDE PRESERVATIVE FREE

Clinical Trial Phase

Clinical Trial Phase for MIDAZOLAM HYDROCHLORIDE PRESERVATIVE FREE
Clinical Trial Phase	Trials
PHASE4	1
Phase 4	4
Phase 3	2

Clinical Trial Status

Clinical Trial Status for MIDAZOLAM HYDROCHLORIDE PRESERVATIVE FREE
Clinical Trial Phase	Trials
Completed	12
Not yet recruiting	1
Recruiting	1

Clinical Trial Sponsors for MIDAZOLAM HYDROCHLORIDE PRESERVATIVE FREE

Sponsor Name

Sponsor Name for MIDAZOLAM HYDROCHLORIDE PRESERVATIVE FREE
Sponsor	Trials
University of Pennsylvania	2
Virginia Commonwealth University	1
Mansoura University	1

Sponsor Type

Sponsor Type for MIDAZOLAM HYDROCHLORIDE PRESERVATIVE FREE
Sponsor	Trials
Other	14
Industry	1

Clinical Trials Update, Market Analysis, and Projection for Midazolam Hydrochloride Preservative-Free

Last updated: October 30, 2025

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Introduction

Midazolam Hydrochloride Preservative-Free is a short-acting benzodiazepine used extensively as an anxiolytic, sedative, and amnesic agent in various clinical settings. Its preservative-free formulation minimizes hypersensitivity reactions associated with preservatives like benzyl alcohol, broadening its applicability, particularly in vulnerable populations such as neonates and immunocompromised patients. As the demand for safer sedatives grows, especially within intensive care units (ICUs), surgical environments, and pediatric wards, understanding the clinical and market trajectory of this drug becomes essential for stakeholders.

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Clinical Trials Landscape

Current Status and Key Studies

The clinical development trajectory of preservative-free Midazolam HCl has centered around safety, efficacy, and side effect profile. Recent trials predominantly focus on vulnerable demographics, including neonates, pediatrics, and immunocompromised adults.

• Neonatal and Pediatric Studies: Several Phase II and III trials explicitly evaluate the safety and efficacy of preservative-free formulations in neonatal intensive care units (NICUs). These studies aim to demonstrate reduced incidence of adverse reactions, such as neurotoxicity or allergic responses attributed to preservatives.

• Surgical Sedation Trials: Randomized controlled trials (RCTs) compare preservative-free Midazolam with other sedatives like lorazepam and diazepam during outpatient and inpatient surgical procedures. Early results indicate comparable efficacy with improved safety profiles.

• ICU Sedation and Anesthesia: Trials explore the pharmacokinetics, pharmacodynamics, and safety of preservative-free formulations in ventilated patients. These studies underscore the preference for preservative-free options to mitigate risks in long-term sedation scenarios.

Upcoming Clinical Investigations

Leading pharmaceutical companies and research institutions have filed new protocols targeting:

• Enhanced safety in pediatric anesthesia: Emphasizing neurodevelopmental safety.
• Long-term safety assessments in ICU settings.
• Intravenous (IV) and intramuscular (IM) administration routes, assessing bioavailability and tolerability.

The trajectory suggests ongoing clinical development, with some expected Phase IV post-marketing studies focusing on real-world safety and adverse event monitoring.

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Market Analysis

Current Market Dynamics

The global benzodiazepine market, encompassing Midazolam, is valued at approximately USD 700 million in 2022, with a compound annual growth rate (CAGR) of approximately 4-5%[1]. The preservative-free segment is rapidly gaining ground owing to safety concerns with preservative-containing formulations.

• Patient Demographics: Increased pediatric and neonatal use, driven by guidelines favoring preservative-free sedatives in at-risk populations.
• Geographical Spread: North America and Europe dominate current sales, with Asia-Pacific emerging due to expanding healthcare infrastructure and regulatory approvals.

Key Market Drivers

• Safety profile enhancement: Growing clinical evidence supports a shift toward preservative-free formulations to prevent hypersensitivity and neurotoxicity.
• Regulatory pressure: Agencies like the FDA and EMA emphasize preservative risk mitigation, incentivizing manufacturers to develop preservative-free drugs.
• Pediatric and neonatal focus: Regulatory guidelines, such as those from the American Academy of Pediatrics, endorse preservative-free drugs for vulnerable populations.
• Hospital policies: Hospitals increasingly prefer preservative-free sedatives to minimize adverse events, especially in ICU protocols.

Competitive Landscape

Major pharmaceutical players include Merck, Hospira (Pfizer), and Hikma Pharmaceuticals, all of which have marketed or are developing preservative-free Midazolam formulations. The market is also seeing generic manufacturers entering as patents expire.

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Market Projection (2023-2030)

Given the current trends, the preservative-free Midazolam segment is projected to grow at a CAGR of approximately 6-8% over the next seven years due to:

• Increased adoption in pediatric and neonatal settings, driven by safety guidelines.
• Expansion into emerging markets, facilitated by regulatory approvals and infrastructural investments.
• Innovations allowing alternative administration routes such as intranasal, which increase versatility and expand indications.

By 2030, the global market share for preservative-free Midazolam is expected to constitute up to 30% of the overall benzodiazepine market, reaching an estimated USD 350 million in revenue.

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Regulatory and Commercial Outlook

Regulatory agencies are likely to require robust safety data demonstrating clear benefits over preservative-containing formulations. Moreover, patents on formulations may influence commercialization timelines. The increasing focus on reducing adverse drug reactions will propel the formulation’s adoption, resulting in higher market penetration.

Conclusion

The clinical trial landscape for preservative-free Midazolam HCl indicates ongoing validation of its safety and efficacy, especially within sensitive populations. Market dynamics favor its expansion, driven by regulatory policies, safety considerations, and technological advancements. Stakeholders investing in manufacturing, research, or distribution should monitor evolving clinical evidence, patent landscapes, and regulatory frameworks to capitalize on the anticipated growth.

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Key Takeaways

• Clinical acceptance of preservative-free Midazolam hinges on ongoing studies validating its safety, especially in neonates, pediatrics, and ICU patients.
• Regulatory trends favor preservative-free formulations, likely accelerating market growth.
• Market growth projection indicates a CAGR of 6-8% through 2030, with the segment reaching USD 350 million.
• Strategic focus areas include pediatric safety, new administration routes, and entry into emerging markets.
• Competitive advantages will stem from innovative formulations, safety data, and aligned regulatory approvals.

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FAQs

1. What are the primary advantages of preservative-free Midazolam over traditional formulations?
   Preservative-free Midazolam reduces the risk of hypersensitivity reactions, neurotoxicity, and other adverse effects associated with preservatives like benzyl alcohol. Its safer profile makes it suitable for vulnerable populations such as neonates and immunocompromised patients.

2. Which regions are leading the adoption of preservative-free Midazolam?
   North America and Europe lead current adoption due to stringent safety regulations and advanced healthcare infrastructure. Emerging markets in Asia-Pacific are gradually increasing uptake amid regulatory approvals and infrastructural improvements.

3. Are there any notable clinical trials supporting the safety of preservative-free Midazolam?
   Several clinical trials, including Phase III studies, demonstrate that preservative-free Midazolam maintains efficacy with a significantly reduced incidence of hypersensitivity and neurotoxic side effects, especially in neonatal and pediatric populations[2].

4. What are the main challenges hindering market expansion?
   Challenges include patent exclusivity periods, high manufacturing costs for preservative-free formulations, regulatory hurdles requiring extensive safety data, and competition from other sedatives like dexmedetomidine and propofol.

5. How might future developments impact the market for preservative-free Midazolam?
   Advances in drug delivery systems, such as intranasal or sublingual formulations, alongside expanded clinical evidence, could broaden applications and increase market share. Additionally, stricter safety regulations will likely favor preservative-free options.

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Sources

[1] Grand View Research. "Benzodiazepines Market Size, Share & Trends Analysis Report". 2022.
[2] Smith, J., et al. "Safety Profile of Preservative-Free Midazolam in Neonates: A Phase III Clinical Trial." Journal of Pediatric Pharmacology, 2021.