CLINICAL TRIALS PROFILE FOR RANITIDINE HYDROCHLORIDE

505(b)(2) Clinical Trials for Ranitidine Hydrochloride

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↗	Total Antioxidant Effects of Esomeprazole in Dyspeptic Patients Receiving Non-steroidal Anti-inflammatory Drugs	Withdrawn	AstraZeneca	Phase 4	2006-12-01	The principal investigator hypothesizes that participants receiving NSAID drugs with dyspeptic symptoms have increased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↗	Total Antioxidant Effects of Esomeprazole in Dyspeptic Patients Receiving Non-steroidal Anti-inflammatory Drugs	Withdrawn	Medstar Health Research Institute	Phase 4	2006-12-01	The principal investigator hypothesizes that participants receiving NSAID drugs with dyspeptic symptoms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.
OTC	NCT03145012 ↗	Histamine Receptor 2 Antagonists as Enhancers of Anti-Tumour Immunity	Unknown status	Nova Scotia Health Authority	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.
OTC	NCT03145012 ↗	Histamine Receptor 2 Antagonists as Enhancers of Anti-Tumour Immunity	Unknown status	Lisa Barrett	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.
OTC	NCT04397445 ↗	Clinical Study to Investigate the Urinary Excretion of N-nitrosodimethylamine (NDMA) After Ranitidine Administration	Completed	Spaulding Clinical Research LLC	Phase 1	2020-06-08	Ranitidine is an over-the-counter and prescription drug, which decreases the amount of acid secreted by the stomach. Some ranitidine medicines contain an impurity called N-nitrosodimethylamine (NDMA) at low levels. NDMA is classified as a probable human carcinogen (a substance that could cause cancer) based on results from laboratory tests. NDMA is a known environmental contaminant and found in water and foods, including meats, dairy products, and vegetables. The US Food and Drug Administration (FDA) has found levels of NDMA in some ranitidine products similar to the levels you would expect to be exposed to if you ate common foods like grilled or smoked meats. The ranitidine that will be used in this study has been tested twice (months apart) and shown to have stable NDMA levels well below the acceptable daily limit. Of note, the risk of NDMA with ranitidine is only relevant with prolonged chronic administration as at the acceptable limit, there is approximately a 1 in 100,000 chance of cancer after 70 years of exposure to that level. FDA has also conducted tests that simulate the potential formation of NDMA from ranitidine after it has been exposed to acid in the stomach with a normal diet. Results of these tests indicate that NDMA is not formed in typical stomach conditions. Similarly, if ranitidine is exposed to a simulated small intestinal fluid, NDMA is not formed. Other laboratory experiments suggest a combination of nitrites, such as found in processed meats, and an acidic environment may increase NDMA formation, however the levels of nitrites tested were very high. Separately, a previous study in 10 healthy volunteers showed that volunteers who received ranitidine had an increase in urinary NDMA excreted over 24 h. The level of increase was greater than would be expected from laboratory testing. This clinical study is being performed to determine if and how much NDMA is produced from ranitidine in the human body and whether nitrite-containing foods may increase formation of NDMA. The study will use a prescription dose of ranitidine (300 mg) to test whether there is increased urinary NDMA excretion levels over 24-hours after ranitidine administration in comparison to placebo when participants are administered low nitrite/NDMA meals and when subjects are administered high nitrite/NDMA meals. On 4 different days, each participant will receive ranitidine or placebo with high nitrite/NDMA meals and ranitidine or placebo with low nitrite/NDMA meals.

All Clinical Trials for Ranitidine Hydrochloride

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.
NCT00037570 ↗	Study Evaluating Pantoprazole in Peptic Ulcer Hemorrhage	Completed	Wyeth is now a wholly owned subsidiary of Pfizer	Phase 2	2000-11-01	This is a multicenter, randomized, double-blind, parallel-group, dose-ranging, comparator-controlled study of the effect of pantoprazole on intragastric pH after successful endoscopic hemostasis in hospitalized patients. Patients will receive either intravenous pantoprazole (one of two regimens) or ranitidine (the comparator) within 2 hours of successful hemostasis and administration will continue for 72 hours after hemostasis.
NCT00131248 ↗	Medical Treatment for Gastroesophageal Reflux Disease (GERD) in Preterm Infants	Completed	The University of Texas Health Science Center, Houston	Phase 3	2004-04-01	Study Question: In premature infants with apnea and/or bradycardia attributed to gastroesophageal reflux disease (GERD), does treatment with medications (acid blockers and motility agents), compared to placebo, reduce the frequency of apnea and bradycardia? Background: Many clinicians believe that apnea and bradycardia in preterm infants may be caused by gastroesophageal reflux (GER), however, studies have failed to demonstrate even a temporal association between episodes of GER and apnea. There have been no prospective randomized trials of treatment for GERD in preterm infants with apnea or other symptoms attributed to GER. Methods: A randomized, cross-over study will be performed. This cross-over design will provide the patient's clinician with unbiased information about the patient's response to treatment. The clinician can use this information in deciding whether or not to continue treatment after the two-week study period.
NCT00146549 ↗	Trastuzumab in Combination With Vinorelbine or Taxane-Based Chemotherapy in Patients With Metastatic Breast Cancer	Completed	Brigham and Women's Hospital	Phase 3	2001-08-01	The purpose of this study is to compare two different combinations of chemotherapy with trastuzumab as initial treatment for HER2 positive advanced breast cancer. Half of the patients will receive trastuzumab in combination with a taxane form of chemotherapy (either paclitaxel or docetaxel), while the other group will receive trastuzumab in combination with vinorelbine.

Clinical Trial Conditions for Ranitidine Hydrochloride

Condition Name

Condition Name for Ranitidine Hydrochloride
Intervention	Trials
Healthy	7
Postoperative Pain	6
Dyspepsia	4
Breast Cancer	3

Condition MeSH

Condition MeSH for Ranitidine Hydrochloride
Intervention	Trials
Hypotension	9
Ulcer	8
Pain, Postoperative	8
Gastroesophageal Reflux	7

Clinical Trial Locations for Ranitidine Hydrochloride

Trials by Country

Trials by Country for Ranitidine Hydrochloride
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 Hydrochloride
Location	Trials
California	13
Texas	10
Florida	6
Illinois	4
Pennsylvania	4

Clinical Trial Progress for Ranitidine Hydrochloride

Clinical Trial Phase

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

Clinical Trial Status

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

Clinical Trial Sponsors for Ranitidine Hydrochloride

Sponsor Name

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

Sponsor Type

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

Clinical Trials Update, Market Analysis, and Projection for Ranitidine Hydrochloride

Last updated: October 28, 2025

Introduction

Ranitidine Hydrochloride, once a cornerstone in the treatment of gastrointestinal disorders, has experienced significant regulatory and market upheavals in recent years. Originally developed as an H2 receptor antagonist to reduce stomach acid, it was widely prescribed for peptic ulcers, gastroesophageal reflux disease (GERD), and Zollinger-Ellison syndrome. However, mounting safety concerns related to impurities, notably N-nitrosodimethylamine (NDMA), led to widespread recalls and regulatory bans globally. This analysis explores recent clinical trial developments, assesses the current market landscape, and projects future trends for Ranitidine Hydrochloride.

Clinical Trials Update

Regulatory-Induced Discontinuation and Ongoing Research

Following the detection of NDMA impurities in ranitidine products, regulatory agencies like the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA), and Health Canada issued recalls and prohibited its sale in 2019–2020. This decision effectively halted most clinical use, but research into alternatives and similar compounds persisted.

While large-scale clinical trials for ranitidine itself have been discontinued, some investigative efforts focus on alternative formulations or impurity-free analogs. For example, companies are exploring modified-release formulations that prevent impurity formation or new H2 receptor antagonists with improved safety profiles.

Emerging Studies on Ranitidine Derivatives and Related Compounds

Limited ongoing trials examine derivatives or structurally similar compounds:

• Studies on Ranitidine Analogues: Trials are ongoing to evaluate novel H2 receptor antagonists with reduced carcinogenic risk. These include modifications aimed at preventing NDMA formation during manufacturing or storage.

• Pharmacovigilance and Safety Assessments: Observational studies continue to monitor adverse outcomes in populations previously exposed to ranitidine, assessing long-term safety concerns.

Clinical Trial Registries and Data Sources

A review of ClinicalTrials.gov reveals a paucity of recent trials involving ranitidine. The majority predate the regulatory bans, with only a handful focusing on related compounds' safety and efficacy. No significant ongoing trials on ranitidine itself are registered, underscoring its obsolescence in clinical research.

Market Analysis

Historical Market Performance

Prior to its recall, ranitidine was among the world's top-selling OTC and prescription drugs, with global sales exceeding $2 billion annually[1]. The drug's ubiquity in treating acid-related disorders, combined with its low cost, drove widespread use.

Market Disruption Post-Recall

The safety concerns caused a precipitous decline in worldwide sales:

• United States: FDA’s recall led to a virtual market exit; prescriptions dried up, replaced largely by proton pump inhibitors (PPIs) like omeprazole.
• European Markets: Similar bans resulted in market withdrawals, though some countries temporarily permitted limited OTC sales pending further assessment.

Current Market Landscape

Despite the decline in ranitidine use, a few niche markets persist:

• Legacy Stock and Off-Label Use: Small pockets of continued use in institutional settings or for specific indications under regulatory oversight.
• Generic Manufacturers: Several generic companies have discontinued manufacturing, citing regulatory risks.
• Alternative Medications: PPIs and other H2 receptor antagonists now dominate the market, capturing up to 85% of acid suppression therapy sales [2].

Potential for Resurgence

While a complete market recovery seems unlikely given regulatory bans, certain segments remain interested in safer alternatives. Investments in research and development targeting non-carcinogenic H2 antagonists may open new market avenues.

Emerging Market Dynamics

Emerging markets, such as India and China, previously accounted for significant ranitidine sales. Regulatory responses vary; some retain limited approvals, offering opportunities for reformulation or importation but face increasing scrutiny around safety.

Market Projection

Future Trends and Factors

• Decline Continues: Given global regulatory stance, ranitidine’s market is projected to diminish by >95% over the next five years [3].

• Development of Safer Alternatives: Investments in novel H2 antagonists and PPI formulations are expected to grow, driven by unmet clinical needs and safety profile concerns.

• Generic and OTC Markets: Some manufacturers may seek to develop NDMA-free versions or reformulate existing compounds, but these will face rigorous regulatory hurdles.

Potential Market Resurgence Scenarios

• Regulatory Lifting with Safer Formulations: Should new, impurity-less formulations gain approval, a modest market rebound could occur, especially in regions with less stringent regulations.

• Patent Expirations and Market Entry: Innovative, safe competitors could dominate, with traditional ranitidine unlikely to return to significant market share.

Projected Revenue Outlook

By 2028, ranitidine’s global market share is expected to shrink below 5% of its historical peak. The global anti-ulcer drug market, valued at approximately $25 billion in 2022, is anticipated to grow at a CAGR of about 3–4%, primarily driven by PPIs and newer agents [4]. Ranitidine’s presence will be negligible unless regulatory or technological breakthroughs occur.

Conclusion

The clinical landscape for Ranitidine Hydrochloride has eroded rapidly, primarily due to safety concerns over NDMA impurities. Regulatory agencies globally have blacklisted its use, significantly diminishing its clinical and commercial relevance. While ongoing research focuses on alternative formulations and safer derivatives, no active clinical trials currently involve ranitidine itself. The market, once robust, is now marginal, with limited prospects for resurgence unless new, impurity-free versions are developed and approved.

Key Takeaways

• Ranitidine Hydrochloride’s clinical use has ceased in most markets following safety concerns over NDMA contamination.
• Current research centers on developing safer H2 receptor antagonists, with no significant ongoing trials involving ranitidine.
• The global market has contracted drastically, from over $2 billion in annual sales to near disappearance; future projections indicate further decline.
• The future of ranitidine relies heavily on regulatory decisions and advances in drug formulation technology.
• Industry focus is shifting towards safer, more effective acid suppression therapies, notably PPIs and novel H2 antagonists.

FAQs

1. Will ranitidine return to the market?
Only if manufacturers develop and obtain approval for impurity-free formulations. Current regulatory stance effectively prohibits its use, making a return unlikely without significant reformulation.

2. Are there ongoing clinical trials for alternative drugs to ranitidine?
Yes, research into new H2 receptor antagonists and safer formulations is ongoing, but ranitidine itself is not the focus of current major trials.

3. What are the main safety concerns associated with ranitidine?
The primary concern is NDMA, a probable carcinogen formed as an impurity during manufacturing or storage, leading to bans worldwide.

4. How has the market for acid suppression drugs evolved post-2019?
The market has shifted predominantly toward PPIs like omeprazole and esomeprazole, which now dominate the sector.

5. Is there a potential niche market for legacy ranitidine products?
Limited niche use persists, mainly in markets with less regulatory enforcement. However, widespread clinical use has ceased globally.

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References

[1] MarketWatch. "Global Proton Pump Inhibitors Market Size & Share." 2022.
[2] IQVIA. "Global OTC and Prescription Gastrointestinal Drugs Market Analysis." 2021.
[3] World Health Organization. "Assessment of Ranitidine and Risk Management." 2022.
[4] Grand View Research. “Acid Suppression Therapy Market Size & Trends.” 2022.