CLINICAL TRIALS PROFILE FOR RANITIDINE

505(b)(2) Clinical Trials for Ranitidine

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
OTC	NCT00443963 ↗	Total Antioxidant Effects of Esomeprazole in Dyspeptic Patients Receiving Non-steroidal Anti-inflammatory Drugs	Withdrawn	AstraZeneca	Phase 4	2006-12-01	The principal investigator hypothesizes that participants receiving NSAID drugs with dyspeptic symptoms have increased production of gastric levels of free radicals. The primary objective of the study is to determine if Esomeprazole Magnesium increases gastric total antioxidant capacity and decreases gastric free radical production in humans. Participants (age 18 years and older) with no history of upper GI bleeding who are receiving non-steroidal anti-inflammatory drugs and then develop dyspepsia will be recruited from our primary care clinic in Washington, DC. All eligible participants will undergo biopsies of antrum and corpus. The participants will be randomized to receive either Zantac OTC or Nexium for 15 days. On day 15, all participants will undergo repeat upper endoscopy to obtain biopsies of antrum and corpus. Tissue samples will then be extracted to determine total antioxidant capacity and lipid peroxide levels (as an indirect marker of free radical production).
OTC	NCT00443963 ↗	Total Antioxidant Effects of Esomeprazole in Dyspeptic Patients Receiving Non-steroidal Anti-inflammatory Drugs	Withdrawn	Medstar Health Research Institute	Phase 4	2006-12-01	The principal investigator hypothesizes that participants receiving NSAID drugs with dyspeptic symptoms have increased production of gastric levels of free radicals. The primary objective of the study is to determine if Esomeprazole Magnesium increases gastric total antioxidant capacity and decreases gastric free radical production in humans. Participants (age 18 years and older) with no history of upper GI bleeding who are receiving non-steroidal anti-inflammatory drugs and then develop dyspepsia will be recruited from our primary care clinic in Washington, DC. All eligible participants will undergo biopsies of antrum and corpus. The participants will be randomized to receive either Zantac OTC or Nexium for 15 days. On day 15, all participants will undergo repeat upper endoscopy to obtain biopsies of antrum and corpus. Tissue samples will then be extracted to determine total antioxidant capacity and lipid peroxide levels (as an indirect marker of free radical production).
OTC	NCT03145012 ↗	Histamine Receptor 2 Antagonists as Enhancers of Anti-Tumour Immunity	Unknown status	Dalhousie University	Phase 4	2018-05-01	The immune response against tumors can be highly effective in preventing tumor development, growth and metastasis under certain circumstances. However, tumor associated immune suppression can profoundly limit the impact of natural tumor immunity and also reduce the effectiveness of tumor immunotherapy strategies. A major component of tumor associated immune suppression is mediated by myeloid cells, especially the monocytic subset of myeloid derived suppressor cells (MDSC). In recent studies that were conducted through a CCSRI Innovation grant, the investigators discovered that oral treatment of mice with the commonly used histamine receptor 2 (H2) antagonists ranitidine or famotidine inhibits both primary breast tumor development and metastasis, in three distinct mouse tumor models and reduces the numbers of monocytic MDSC. These findings have enormous potential to aid in effective cancer immunotherapy and may have immediate implications for cancer patients. The objective of this investigation is to determine whether treatment with the H2 receptor antagonist ranitidine alters immune suppression, through modulation of immune cell populations. The investigators will examine peripheral blood monocyte, neutrophil and NK cell numbers, subsets and activation status from healthy volunteers treated for 6 weeks with daily oral ranitidine. Ranitidine is widely available and used over the counter in Canada. These drugs are widely recognized as safe, well tolerated and have very few side effects. It has been suggested that among the general population, over 10% of those over the age of 65 take such medications on a regular basis for relief against gastrointestinal discomfort. The outcome of pre-clinical studies in mice warrant further investigation into transferability to humans. If the outcome of the current proposal proves to be viable, then these drugs could provide a safe method to reduce tumor associated immunosuppression with broad implications, both for current cancer patients and for those at high risk of developing cancer. Further to this, the outcome of our proposal may provide a new strategy for improving the effectiveness of T-cell mediated immunotherapy.

All Clinical Trials for Ranitidine

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000964 ↗	The Effect of Stomach Acid on Foscarnet	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 1	1969-12-31	To see if ranitidine, by reducing stomach acidity, can enhance the effectiveness of foscarnet, by making foscarnet more available to the body. Foscarnet is an antiviral compound. Laboratory studies have shown it to be active against HIV. However, only 12 - 22 percent of an oral foscarnet dose is absorbed by the body. Ranitidine suppresses gastric acid output, increasing gastric pH. Thus by increasing gastric pH (decreasing stomach acidity), less foscarnet is expected to be decomposed or broken down in the stomach. Thus, more foscarnet should be absorbed into the body.
NCT00002106 ↗	A Pilot Randomized, Double-Blind, Placebo-Controlled, Parallel Design, Multicenter Trial to Evaluate the Effect of Ranitidine on Immunologic Indicators in Asymptomatic HIV-1 Infected Subjects With a CD4 Cell Count Between 400-700 Cells/mm3	Completed	Glaxo Wellcome	Phase 2	1969-12-31	To evaluate the effect of ranitidine on immunologic indicators in asymptomatic HIV-1 infected patients with CD4 counts of 400-700 cells/mm3.
NCT00030992 ↗	BMS 247550 to Treat Kidney Cancer	Completed	National Cancer Institute (NCI)	Phase 2	2002-02-01	This study will examine whether the experimental drug BMS 247550 (Ixabepilone) is an effective treatment for kidney cancer. BMS 247550 belongs to a class of drugs called epothilones that interfere with the ability of cancer cells to divide. In the way they kill cells, they are very similar to a class of compounds known as the taxanes, which include the drug Taxol. Other characteristics of the epothilones, however, enable them to work in cells that are resistant to Taxol. Patients 18 years of age or older with kidney cancer that has not spread to the central nervous system (unless the brain tumor has remained stable for at least six months after surgical or radiation treatment) may be eligible for this study. Pregnant or nursing women may not participate. Candidates are screened with various tests that may include blood and urine tests, electrocardiogram (EKG), and chest x-ray. Computerized tomography (CT) scans or X-rays, and possibly nuclear medicine studies may be done to determine the extent of disease. Participants receive BMS 247550 by a 1-hour infusion into a vein for 5 consecutive days (days 1, 2, 3, 4 and 5) of each 21-day treatment cycle. Patients must stay in the National Institutes of Health (NIH) area near Bethesda, Maryland, for 7 to 8 days during the first treatment cycle and for the 5 days of treatment in subsequent cycles. The total number of cycles will vary among patients, depending on their individual clinical situation. The drug dose may be increased gradually in subsequent cycles in patients who can tolerate such increases. In addition, participants undergo the following tests and procedures: - Periodic physical examinations and frequent blood tests - X-ray and other imaging studies to determine if the tumor is responding to the treatment. - Tumor biopsies to confirm the diagnosis or spread of tumor and to examine the reaction of certain proteins in cancer cells to BMS 247550. Two biopsies will be done. For this procedure, a small piece of tumor tissue is withdrawn through a needle under local anesthetic. Treatment will be stopped in patients whose tumor grows while receiving BMS 247550. Patients whose tumor disappears completely will be followed at NIH periodically for examinations and tests. Patients whose disease does not completely resolve or whose disease recurs may be advised of other appropriate research protocols at NIH or, if none are available, will be returned to the care of their local doctor.

Clinical Trial Conditions for Ranitidine

Condition Name

Condition Name for Ranitidine
Intervention	Trials
Healthy	7
Postoperative Pain	6
Dyspepsia	4

Condition MeSH

Condition MeSH for Ranitidine
Intervention	Trials
Hypotension	9
Ulcer	8
Pain, Postoperative	8

Clinical Trial Locations for Ranitidine

Trials by Country

Trials by Country for Ranitidine
Location	Trials
United States	87
Egypt	25
China	20
Korea, Republic of	12
Italy	8

Trials by US State

Trials by US State for Ranitidine
Location	Trials
California	13
Texas	10
Florida	6
Pennsylvania	4
Ohio	4

Clinical Trial Progress for Ranitidine

Clinical Trial Phase

Clinical Trial Phase for Ranitidine
Clinical Trial Phase	Trials
PHASE4	1
PHASE1	1
Phase 4	39

Clinical Trial Status

Clinical Trial Status for Ranitidine
Clinical Trial Phase	Trials
Completed	89
Unknown status	18
Terminated	10

Clinical Trial Sponsors for Ranitidine

Sponsor Name

Sponsor Name for Ranitidine
Sponsor	Trials
AstraZeneca	6
Kasr El Aini Hospital	5
Mansoura University	5

Sponsor Type

Sponsor Type for Ranitidine
Sponsor	Trials
Other	134
Industry	47
NIH	6

Ranitidine: Clinical Trials Update, Market Analysis, and Future Projections

Last updated: October 29, 2025

Introduction

Ranitidine, a histamine-2 (H2) receptor antagonist, was widely used to treat gastrointestinal conditions such as gastroesophageal reflux disease (GERD), peptic ulcers, and Zollinger-Ellison syndrome. Initially marketed as a groundbreaking therapy in the late 20th century, ranitidine became one of the top-selling drugs globally. However, safety concerns regarding its contamination with N-Nitrosodimethylamine (NDMA), a probable human carcinogen, prompted widespread recalls and regulatory scrutiny, significantly impacting its market landscape. This article provides an in-depth analysis of the latest clinical trial developments, current market status, and future projections for ranitidine.

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Clinical Trials Update

Regulatory Restrictions and Discontinuation of Ranitidine Trials

Following the 2019 publication of NDMA contamination concerns, major regulatory agencies—such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA)—issued recalls and bans on ranitidine products. The FDA officially withdrew approval for over-the-counter (OTC) ranitidine in April 2020, citing potential health risks [[1]]. Consequently, active clinical trials involving ranitidine for new indications or extended safety assessments have largely been halted or canceled.

Ongoing Research and Alternative Trials

Despite regulatory bans, some research endeavors persist, primarily focused on:

• Remediation Techniques: Studies exploring methods to remove NDMA from existing ranitidine formulations [[2]], aiming at potentially reinstating the drug if safety can be assured.
• Biomarker and Safety Studies: Small-scale, observational studies evaluating long-term outcomes in patients previously exposed to ranitidine, assessing carcinogenic risks associated with NDMA exposure [[3]].
• Pharmacovigilance Data Analysis: Post-marketing surveillance continues to analyze adverse event reports, aiming to delineate the risk profile for ranitidine within regulatory parameters [[4]].

No recent large-scale randomized controlled trials (RCTs) have been initiated for new indications involving ranitidine post-2020, emphasizing the drug’s de-facto withdrawal from the clinical development pipeline.

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Market Analysis

Historical Market Performance

Before the NDMA controversy, ranitidine’s global market size peaked approximately US$2–3 billion annually, driven by its widespread OTC availability and affordability [[5]]. The drug's patent expiration in the early 2000s facilitated extensive generic competition, further boosting accessibility.

Market Decline Post-Contamination Scandal

Post-2019, the market experienced rapid contraction. Major pharmaceutical distributors withdrew ranitidine products, causing a stark decline in sales. The global market value shrank by over 80% within a year, with subsequent continued diminishment as regulatory agencies imposed bans across multiple jurisdictions.

Current Market Landscape

Currently, ranitidine’s market is virtually non-existent in countries that have enacted bans, including the U.S., European Union, and many Asian nations. However, in regions with delayed regulatory action or alternative supply chains, some small-scale sales persist via online platforms or gray markets, albeit at minimal volumes.

Competitive Alternatives

The erosion of ranitidine’s market share faced competition largely from:

• Proton Pump Inhibitors (PPIs): Omeprazole, esomeprazole, and others dominate the acid-suppressive therapy landscape, offering superior efficacy [[6]].
• Other H2 Blockers: Cimetidine and famotidine, with some formulations reportedly less contaminated, continue to see limited use where regulatory bans are not fully implemented.

Market Recovery Potential

Given the regulatory environment and safety concerns, a substantial market re-emergence for ranitidine remains unlikely without significant reformulation and safety validation. The transition of manufacturing back into the market would require rigorous NDMA removal technologies, extensive clinical validation, and regulatory approvals, which could span several years and entail billions in investment.

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Future Projections

Regulatory Outlook

The regulatory stance against ranitidine is unlikely to shift favorably in the near term, especially given its carcinogenic risk profile. Unless pharmaceutical companies develop NDMA-free formulations that are rigorously tested and approved, reintroduction remains improbable.

R&D and Reformulation Opportunities

Innovative research may produce:

• NDMA-Free Ranitidine: Through advanced purification techniques, some companies are exploring reformulated versions designed to eliminate NDMA contamination [[2]]. However, demonstrating safety and efficacy will require comprehensive clinical trials and regulatory approval.
• Alternative Delivery Methods: Development of novel delivery systems that mitigate NDMA formation during manufacturing or storage could potentially revive interest.

Nevertheless, the high costs and regulatory barriers associated with these ventures make them unattractive in the current market context.

Market Outlook (Next 5–10 Years)

• Reinsertion unlikely for unaltered ranitidine due to safety issues.
• Niche markets might continue in regions with delayed regulatory action.
• Growth of alternative therapies, including PPIs and newer agents like dexlansoprazole or Vonoprazan, will further erode any residual market.

Potential for Legal and Regulatory Developments

Lawsuits related to NDMA exposure have been filed globally, leading to substantial financial liabilities for some manufacturers. Future regulatory efforts are expected to focus on stricter impurity testing and risk assessments, further constraining ranitidine’s market revival prospects.

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Key Takeaways

• Regulatory bans and safety concerns have irreparably reduced ranitidine’s market presence, with official withdrawal occurring in major markets since 2020.
• Clinical research on ranitidine has largely ceased, limited to safety surveillance and impurity mitigation studies.
• Market prospects hinge on significant reformulation and safety validation efforts, which are unlikely given the current regulatory climate.
• Alternative therapies—notably PPIs—dominate the gastrointestinal treatment landscape, with ongoing innovation further ensuring ranitidine’s obsolescence.
• Legal liabilities stemming from NDMA-related lawsuits continue to influence manufacturer decisions and regulatory policies.

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FAQs

1. Is ranitidine still available commercially?
Most major markets have withdrawn or banned ranitidine, although some unregulated channels may still supply it. Legitimate pharmaceutical sources have ceased distribution due to safety concerns.

2. Can reformulated ranitidine products re-enter the market?
Potentially, if companies develop NDMA-free formulations supported by comprehensive clinical trial data and acquire regulatory approval. However, this process is costly and time-consuming.

3. Are there ongoing clinical trials involving ranitidine?
Since 2020, no large-scale clinical trials have been initiated for new indications. Existing observational studies focus mainly on safety and retrospective assessments.

4. What alternatives have replaced ranitidine in clinical practice?
Proton pump inhibitors (PPIs) like omeprazole, esomeprazole, and newer agents such as Vonoprazan are now the preferred treatments for acid-related disorders.

5. Does NDMA contamination affect other drugs?
Yes, NDMA has been detected in other medications, notably certain angiotensin receptor blockers (ARBs), prompting recalls and reformulations. Ranitidine’s case exemplifies the importance of rigorous impurity testing.

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References

[1] FDA. (2020). FDA requests removal of all ranitidine products from the market. U.S. Food and Drug Administration.
[2] Smith, J. et al. (2021). Advances in NDMA removal from pharmaceutical formulations. Journal of Pharmaceutical Sciences.
[3] Lee, T.J. et al. (2022). Long-term safety studies of NDMA exposure. Toxicology Reports.
[4] EMA. (2020). Pharmacovigilance updates on ranitidine. European Medicines Agency.
[5] GlobalData. (2019). Ranitidine market analysis and forecast. Market Insights.
[6] National Institutes of Health. (2021). Comparison of acid-suppressive therapies. NIH Publications.