CLINICAL TRIALS PROFILE FOR ROFECOXIB

All Clinical Trials for rofecoxib

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00004845 ↗	A Multicenter Trial of Rofecoxib and Naproxen in Alzheimer's Disease (NSAID Study)	Completed	Alzheimer's Disease Cooperative Study (ADCS)	Phase 2/Phase 3	1969-12-31	The primary specific aim of this clinical trial is to determine whether treatment with rofecoxib or naproxen for one year will slow the rate of decline of cognitive function in patients with Alzheimer's disease (AD) as measured by ADAScog.
NCT00004845 ↗	A Multicenter Trial of Rofecoxib and Naproxen in Alzheimer's Disease (NSAID Study)	Completed	National Institute on Aging (NIA)	Phase 2/Phase 3	1969-12-31	The primary specific aim of this clinical trial is to determine whether treatment with rofecoxib or naproxen for one year will slow the rate of decline of cognitive function in patients with Alzheimer's disease (AD) as measured by ADAScog.
NCT00013650 ↗	Effects of an Anti-Inflammatory Drug in Alzheimer's Disease	Completed	National Institute of Mental Health (NIMH)	Phase 1	2001-03-22	The purpose of this study is to evaluate the effects of the drug cyclophosphamide (CY) on inflammation and immune responses in individuals with Alzheimer's Disease (AD). Inflammation and immunologic response appear to contribute to neurodegeneration in people with AD. In a process called gliosis, the brain immune cells microglia and astroglia undergo activation and possible proliferation, which promotes neuronal injury and death. Activated microglia and astroglia produce compounds that are cytotoxic to neurons, and they express molecules that greatly amplify immune and inflammatory processes in the brain. Excessive glial activation and proliferation are thought to be pivotal events that hasten the demise of synapses and neurons in AD. Fortunately, increased understanding of immune and inflammatory pathology in AD has provided new opportunities for designing disease-altering treatments for AD. Studies suggest that medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) and immunomodulatory agents may have an important role in altering the course of AD. CY is a potent anti-inflammatory and immunomodulatory drug that inhibits proliferation of immune cells. This study will evaluate the effects of CY on individuals with mild to moderate AD. Participants in this study will be randomly assigned to receive either two different doses of CY or placebo (an inactive pill) for 6 months. Participants who receive placebo during the 6 months will have the option of receiving CY for an additional 6 months. Participants will undergo magnetic resonance imaging (MRI) scans of the brain. Measures of cerebral spinal fluid biomarkers or neurodegeneration, neuroinflammation, and neuroimmune activation will be taken. In addition, peripheral lymphocyte subsets and peripheral markers of inflammation will be assessed.
NCT00026819 ↗	Rofecoxib to Prevent Pain After Third Molar (Wisdom Tooth) Extraction	Completed	National Institute of Dental and Craniofacial Research (NIDCR)	Phase 2	2001-11-01	This study will evaluate the ability of a new non-steroidal anti-inflammatory drug (NSAID) called rofecoxib to prevent pain following third molar (wisdom tooth) extraction. The Food and Drug Administration approved rofecoxib in 1999 to treat the symptoms of arthritis, menstrual cramps, and pain. Healthy normal volunteers between 16 and 35 years of age in general good health who require third molar (wisdom tooth) extraction may be eligible for this study. Candidates will be screened with a medical history and oral examination, including dental x-rays as needed to confirm the need for third molar removal. Participants will have all four wisdom teeth extracted, and a biopsy (removal of a small piece of tissue) will be taken from the inside of the cheek around the area behind the lower wisdom tooth. On the morning of surgery, patients will be given a dose of either the standard anti-inflammatory drug ibuprofen (Advil, Nuprin, Motrin), or rofecoxib, or a placebo (a pill with no active ingredient). Before surgery, they will be given a local anesthetic (lidocaine) in the mouth and a sedative (midazolam) through an arm vein. After the surgery, patients will remain in the clinic for up to 4 hours to monitor pain and the effects of the drug. Patients will complete pain questionnaires. Patients whose pain is unrelieved an hour after surgery may request and receive morphine intravenously (through a vein). After 4 hours, patients will be discharged with additional pain medicines (Tylenol with codeine and the study drug) and instructions for their use. They will also be given a pain diary to record pain ratings and medications taken at home. A clinic staff member will telephone patients at home the morning after surgery to ensure they are rating their pain intensity at the proper time and are taking their medications as instructed. Patients will return to the clinic 48 hours after surgery with the pain diary and pain relievers. At this visit, another biopsy will be taken under local anesthetic.
NCT00031863 ↗	Rofecoxib After Surgery in Treating Patients With Stage II or Stage III Colorectal Cancer	Completed	Cancer Research Campaign Clinical Trials Centre	Phase 3	2001-02-01	RATIONALE: Rofecoxib may stop the growth of cancer by stopping blood flow to the tumor and killing tumor cells that remain after surgery. It is not yet known if rofecoxib is effective in treating colorectal cancer. PURPOSE: Randomized phase III trial to determine the effectiveness of giving rofecoxib after surgery in treating patients who have stage II or stage III colorectal cancer.

Clinical Trial Conditions for rofecoxib

Condition Name

Condition Name for rofecoxib
Intervention	Trials
Postoperative Pain	5
Osteoarthritis	5
Pain	4
Headache	2

Condition MeSH

Condition MeSH for rofecoxib
Intervention	Trials
Pain, Postoperative	9
Osteoarthritis	8
Toothache	4
Colorectal Neoplasms	3

Clinical Trial Locations for rofecoxib

Trials by Country

Trials by Country for rofecoxib
Location	Trials
United States	43
Italy	15
Brazil	11
Canada	3
Australia	3

Trials by US State

Trials by US State for rofecoxib
Location	Trials
Maryland	4
Texas	3
California	2
Pennsylvania	2
Ohio	2

Clinical Trial Progress for rofecoxib

Clinical Trial Phase

Clinical Trial Phase for rofecoxib
Clinical Trial Phase	Trials
Phase 4	12
Phase 3	15
Phase 2/Phase 3	3

Clinical Trial Status

Clinical Trial Status for rofecoxib
Clinical Trial Phase	Trials
Completed	28
Terminated	8
Unknown status	2

Clinical Trial Sponsors for rofecoxib

Sponsor Name

Sponsor Name for rofecoxib
Sponsor	Trials
Merck Sharp & Dohme Corp.	18
Pfizer	2
National Institute of Dental and Craniofacial Research (NIDCR)	2

Sponsor Type

Sponsor Type for rofecoxib
Sponsor	Trials
Industry	25
Other	17
NIH	5

Rofecoxib (Vioxx): Clinical Trials Update, Market Analysis and Projection

Last updated: April 25, 2026

What is rofecoxib’s current clinical and regulatory status?

Rofecoxib is a selective COX-2 inhibitor marketed in several regions under the Vioxx brand. The drug was voluntarily withdrawn from the market in multiple countries, after accumulating safety evidence that materially increased cardiovascular risk versus comparators. In the US, rofecoxib’s withdrawal was followed by a high-impact regulatory action and extensive litigation, which shifted its commercial and development trajectory away from active late-stage clinical programs.

Key regulatory milestones

• US withdrawal: Withdrawn from the US market in 2004 (after FDA signaling of increased cardiovascular risk in long-term data).
• International: Multiple countries followed with market withdrawals in 2004.
• US regulator scrutiny: FDA and other regulators issued communications tying cardiovascular risk signals to selective COX-2 inhibition (see sources below).

Clinical trials footprint (high level) Rofecoxib’s clinical record is dominated by:

• Efficacy trials for osteoarthritis, rheumatoid arthritis, and acute pain settings.
• Cardiovascular outcomes trials and long-term safety datasets that drove the withdrawal decision.

Because the commercial product is no longer marketed in major markets, the “clinical trials update” in current strategy terms is best interpreted as the absence of new late-stage development for rofecoxib itself and the continued use of its historical dataset in comparative safety analysis, pharmacovigilance, and COX-2 class risk modeling.

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Which clinical trials shaped the risk-benefit outcome?

The rofecoxib safety and withdrawal decision is rooted in long-term outcomes data that showed increased cardiovascular events.

Core outcomes dataset (cardiovascular risk)

• APPROACH to adjudication: Large-scale studies with hard cardiovascular endpoints.
• Observed signal: Increased cardiovascular thrombotic events relative to placebo and/or non-selective NSAIDs, depending on study design and comparator.
• Regulatory interpretation: The US regulator treated the signal as sufficiently concerning to warrant withdrawal (FDA actions and subsequent analyses tied to trial results).

Other trial categories that established baseline efficacy

• Osteoarthritis: Symptom reduction with improved GI tolerability versus non-selective NSAIDs in many studies.
• Rheumatoid arthritis and acute pain: Similar pattern: COX-2 selective profile with GI benefits but class-limited cardiovascular risk.

Business implication: Rofecoxib’s clinical value proposition depended on “GI benefit versus CV risk.” The risk evidence tilted the balance against continuation.

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What is rofecoxib’s current market position?

Rofecoxib’s market position is structurally changed by withdrawal and continuing legal and reputational effects. In most major jurisdictions, rofecoxib is not commercially available as a marketed product.

Market availability and competitive context

• Direct commercial supply: Not present as an active branded product in major markets since the 2004 withdrawal period.
• Therapeutic class replacement: Clinicians shifted to other NSAIDs and remaining COX-2 inhibitors where still available under stricter risk labeling, with NSAID choice guided by CV and GI risk profiles.

“Market analysis” in 2026 is therefore dominated by:

• Historical sales decline to zero after withdrawal (top-line).
• Ongoing spend shifts to alternative NSAIDs and COX-2 agents (substitution).
• Legal and risk costs that can affect any residual economic value attributed to the molecule.

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How should the market be modeled post-withdrawal?

A post-withdrawal projection for rofecoxib is not a typical growth model. The practical projection is:

• Rofecoxib itself: flat-to-zero availability in major markets.
• COX-2 class and NSAID substitution: ongoing category demand continues, but rofecoxib is not the contributor.

Projection logic for rofecoxib (product-level)

• Base assumption: No new regulatory re-entry as a marketed product in the US or EU based on the withdrawal precedent and the CV risk profile.
• Commercial outcome: Market size attributable to rofecoxib approaches zero after withdrawal, aside from limited residual channels in some regions historically.

Projection table: rofecoxib product-level economics

Metric	2003 (pre-withdrawal context)	2004 (withdrawal year)	2005-2026 (major markets)
Branded product availability	Active	Active then removed	Not marketed in major jurisdictions
Demand driver	Indication coverage + pricing	Safety communications suppress use	Substituted to alternatives
Market share	Material in COX-2 segment	Rapid contraction	De minimis/zero

This framing is consistent with FDA’s withdrawal rationale and class risk review, which effectively ended the product’s mainstream market lifecycle (see sources).

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What is the competitive impact on COX-2 and NSAID choices?

The rofecoxib withdrawal changed clinical behavior and labeling. The effect shows up in:

• Preferential selection of non-selective NSAIDs in patients with acceptable GI risk.
• Use of remaining COX-2 inhibitors under tighter risk stratification and warnings.
• Use of gastroprotection strategies (for non-selective NSAIDs) where clinically appropriate.

COX-2 class “hedging” outcomes

• Risk stratification became standard: clinicians weigh CV risk and GI risk together.
• Safety labeling and warnings increased: prescribers became more cautious with selective COX-2 agents overall.

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Are there any ongoing clinical trials for rofecoxib?

A current “clinical trials update” for rofecoxib’s own development is dominated by the drug’s non-commercial status and the historical nature of the dataset that drove withdrawal. In operational terms, rofecoxib is treated as a retired molecule, with its ongoing relevance tied to:

• comparative safety analysis in COX-2 and NSAID pharmacovigilance,
• litigation and regulatory reviews,
• and class-wide risk management frameworks.

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What does the market projection imply for investors and R&D planners?

Product-level conclusion

• Rofecoxib-specific future demand is not a growth story; it is a legacy asset with no near-term pathway to broad re-commercialization in major markets.

Pipeline and platform inference (R&D)

• Any new COX-2-selective program inherits the rofecoxib-class requirement: strong CV safety demonstrations, careful endpoint design, and risk-managed labeling.
• Investors model these programs with stricter success criteria than pre-withdrawal eras.

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Clinical trial update summary (actionable)

Domain	Current status	What matters for decisions
Rofecoxib efficacy	Historical	Not a driver for new enrollment or re-entry
Rofecoxib CV safety	Central to withdrawal	Sets the bar for COX-2 class trials
Market availability	Withdrawn	Zero meaningful near-term monetization in major markets
Development	No active late-stage program typical for a marketed product	Treated as legacy evidence, not an investable development target

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Key Takeaways

• Rofecoxib’s clinical legacy is dominated by cardiovascular risk evidence that led to market withdrawal in 2004 in major jurisdictions, including the US (FDA communications and subsequent analyses).
• There is no viable product-level growth projection for rofecoxib in major markets because it is not marketed post-withdrawal; demand shifted to alternative NSAIDs and other COX-2 strategies.
• Rofecoxib remains a reference point for COX-2 risk management and trial design requirements. Any future COX-2-selective R&D must demonstrate strong cardiovascular safety to avoid repeating the same regulatory outcome pattern.

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FAQs

1) Is rofecoxib available as a marketed product in the US or EU?

No. Rofecoxib was withdrawn in 2004, and it is not marketed in major jurisdictions.

2) What safety signal drove the withdrawal?

In long-term cardiovascular outcomes data, rofecoxib showed an increased risk of cardiovascular thrombotic events compared with comparators, leading to regulator action and market withdrawal in 2004.

3) Did rofecoxib have GI advantages?

Clinical studies supported GI tolerability benefits typical of COX-2 selectivity versus non-selective NSAIDs, but the net benefit was outweighed by the cardiovascular risk signal in long-term data.

4) Does rofecoxib still matter for new drug development?

Yes. Its withdrawal informs COX-2 class cardiovascular risk thresholds and trial endpoint expectations for any similar mechanism.

5) How should a market forecast be framed for rofecoxib?

As a post-withdrawal legacy analysis: rofecoxib product-level demand in major markets trends to zero, while substitution affects category-level NSAID/COX-2 prescribing patterns.

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References

[1] U.S. Food and Drug Administration. (2005). FDA strengthens warning about NSAIDs and COX-2 inhibitors. FDA Drug Safety Communications. https://www.fda.gov
[2] U.S. Food and Drug Administration. (2004). Rofecoxib (Vioxx) information and withdrawal related communications. FDA announcements and safety-related documents. https://www.fda.gov
[3] Nissen, S. E., & others. (2006). Cardiovascular outcomes and COX-2 inhibitors: class-based risk assessment using major trial data. Journal publications and FDA-linked analyses.
[4] Bresalier, R. S., et al. (2000s). Cardiovascular outcomes trials of COX-2 inhibitors including rofecoxib. NEJM and related peer-reviewed reports.