CLINICAL TRIALS PROFILE FOR ISONIAZID; PYRAZINAMIDE; RIFAMPIN

All Clinical Trials for isoniazid; pyrazinamide; rifampin

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000636 ↗	Prophylaxis Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Confirmed Latent Tuberculous Infection	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	1969-12-31	To evaluate and compare the effectiveness of a 2-month regimen of rifampin and pyrazinamide versus a 1-year course of isoniazid (INH) to prevent the development of tuberculosis in patients who are coinfected with HIV and latent Mycobacterium tuberculosis (MTb). Current guidelines recommend 6 to 12 months of treatment with INH for purified protein derivative (PPD)-positive individuals. Problems with this treatment include compliance, adverse reaction, and the possibility of not preventing disease due to INH-resistant organisms. Studies suggest that two or three months of rifampin and pyrazinamide may be more effective than longer courses of INH. A two-month prevention course should help to increase compliance. In addition, the use of two drugs (rifampin and pyrazinamide) may help overcome problems with drug resistance.
NCT00000638 ↗	Preventive Treatment Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Confirmed Latent Tuberculous Infection	Completed	Hoechst Marion Roussel	N/A	1969-12-31	To evaluate and compare the safety and effectiveness of a one-year course of isoniazid (INH) versus a two-month course of rifampin plus pyrazinamide for the prevention of reactivation tuberculosis in individuals infected with both HIV and latent (inactive) Mycobacterium tuberculosis. Current guidelines from the American Thoracic Society and the Centers for Disease Control recommend 6 to 12 months of INH for PPD (purified protein derivative)-positive individuals. Although the effectiveness of this treatment is not known for HIV-infected individuals, several studies using INH to prevent tuberculosis in presumably normal hosts have shown 60 to 80 percent effectiveness. Problems with this treatment include compliance, adverse reaction, and the possibility of not preventing disease due to tuberculosis organisms being resistant to INH. A two-month preventive treatment plan should help in increasing compliance. In addition, the use of two drugs (rifampin / pyrazinamide) may help overcome problems with drug resistance. If this study shows equal or greater effectiveness of the two-month rifampin / pyrazinamide treatment, it could alter the approach to tuberculosis prevention for both HIV-positive and HIV-negative individuals.
NCT00000638 ↗	Preventive Treatment Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Confirmed Latent Tuberculous Infection	Completed	Lederle Laboratories	N/A	1969-12-31	To evaluate and compare the safety and effectiveness of a one-year course of isoniazid (INH) versus a two-month course of rifampin plus pyrazinamide for the prevention of reactivation tuberculosis in individuals infected with both HIV and latent (inactive) Mycobacterium tuberculosis. Current guidelines from the American Thoracic Society and the Centers for Disease Control recommend 6 to 12 months of INH for PPD (purified protein derivative)-positive individuals. Although the effectiveness of this treatment is not known for HIV-infected individuals, several studies using INH to prevent tuberculosis in presumably normal hosts have shown 60 to 80 percent effectiveness. Problems with this treatment include compliance, adverse reaction, and the possibility of not preventing disease due to tuberculosis organisms being resistant to INH. A two-month preventive treatment plan should help in increasing compliance. In addition, the use of two drugs (rifampin / pyrazinamide) may help overcome problems with drug resistance. If this study shows equal or greater effectiveness of the two-month rifampin / pyrazinamide treatment, it could alter the approach to tuberculosis prevention for both HIV-positive and HIV-negative individuals.
NCT00000638 ↗	Preventive Treatment Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Confirmed Latent Tuberculous Infection	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	1969-12-31	To evaluate and compare the safety and effectiveness of a one-year course of isoniazid (INH) versus a two-month course of rifampin plus pyrazinamide for the prevention of reactivation tuberculosis in individuals infected with both HIV and latent (inactive) Mycobacterium tuberculosis. Current guidelines from the American Thoracic Society and the Centers for Disease Control recommend 6 to 12 months of INH for PPD (purified protein derivative)-positive individuals. Although the effectiveness of this treatment is not known for HIV-infected individuals, several studies using INH to prevent tuberculosis in presumably normal hosts have shown 60 to 80 percent effectiveness. Problems with this treatment include compliance, adverse reaction, and the possibility of not preventing disease due to tuberculosis organisms being resistant to INH. A two-month preventive treatment plan should help in increasing compliance. In addition, the use of two drugs (rifampin / pyrazinamide) may help overcome problems with drug resistance. If this study shows equal or greater effectiveness of the two-month rifampin / pyrazinamide treatment, it could alter the approach to tuberculosis prevention for both HIV-positive and HIV-negative individuals.

Clinical Trial Conditions for isoniazid; pyrazinamide; rifampin

Condition Name

Condition Name for isoniazid; pyrazinamide; rifampin
Intervention	Trials
Tuberculosis	22
Tuberculosis, Pulmonary	8
HIV Infections	7
Pulmonary Tuberculosis	6

Condition MeSH

Condition MeSH for isoniazid; pyrazinamide; rifampin
Intervention	Trials
Tuberculosis	39
Tuberculosis, Pulmonary	18
HIV Infections	8
Infections	7

Clinical Trial Locations for isoniazid; pyrazinamide; rifampin

Trials by Country

Trials by Country for isoniazid; pyrazinamide; rifampin
Location	Trials
United States	119
China	39
South Africa	19
Canada	16
Brazil	10

Trials by US State

Trials by US State for isoniazid; pyrazinamide; rifampin
Location	Trials
New York	10
California	10
Texas	9
Maryland	8
New Jersey	7

Clinical Trial Progress for isoniazid; pyrazinamide; rifampin

Clinical Trial Phase

Clinical Trial Phase for isoniazid; pyrazinamide; rifampin
Clinical Trial Phase	Trials
PHASE3	2
Phase 4	7
Phase 3	9

Clinical Trial Status

Clinical Trial Status for isoniazid; pyrazinamide; rifampin
Clinical Trial Phase	Trials
Completed	23
Recruiting	6
Not yet recruiting	5

Clinical Trial Sponsors for isoniazid; pyrazinamide; rifampin

Sponsor Name

Sponsor Name for isoniazid; pyrazinamide; rifampin
Sponsor	Trials
Centers for Disease Control and Prevention	8
National Institute of Allergy and Infectious Diseases (NIAID)	8
Johns Hopkins University	5

Sponsor Type

Sponsor Type for isoniazid; pyrazinamide; rifampin
Sponsor	Trials
Other	120
U.S. Fed	12
NIH	9

Clinical Trials Update, Market Analysis, and Projections for Isoniazid, Pyrazinamide, and Rifampin

Last updated: November 1, 2025

Introduction

Isoniazid, pyrazinamide, and rifampin are cornerstone drugs in the treatment of tuberculosis (TB), a global health challenge responsible for over 1.5 million deaths annually. As multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) pose increasing threats, ongoing clinical evaluations, market dynamics, and future projections for these drugs are crucial for stakeholders—including pharmaceutical companies, healthcare providers, policymakers, and investors.

This analysis synthesizes recent clinical trial updates, current market landscapes, and future outlooks for these pivotal anti-tuberculosis agents.

Clinical Trials Update

Isoniazid

Isoniazid remains a foundational first-line anti-TB drug, with ongoing clinical trials primarily focused on optimizing dosing regimens, improving efficacy in resistant strains, and exploring novel formulations.

Recent studies bolster its role in latent TB infection (LTBI) management. The PREVENT TB trial (NCT03432137) evaluated high-dose isoniazid for LTBI, showing improved adherence with shorter treatment protocols.^[1] Additionally, research into hepatic safety profiles, especially among populations with comorbid conditions, continues, aiming to mitigate hepatotoxicity risks associated with isoniazid.

Emerging trials also explore its use as a partner drug in novel combination therapies targeting MDR-TB, such as the BPaL regimen (bedaquiline, pretomanid, and linezolid), where isoniazid’s role is being reevaluated.

Pyrazinamide

Pyrazinamide’s unique mechanism targeting dormant bacteria enhances sterilizing activity. Recent clinical efforts center on combating resistance challenges and optimizing duration of therapy.

Trials such as NCT03991261 investigate pyrazinamide dosing adjustments to heighten efficacy and reduce hepatic toxicity, particularly among patients with comorbidities.^[2] Efforts to develop pyrazinamide-based formulations with better bioavailability are also underway to improve adherence.

Additionally, an international multicenter study assesses the efficacy of pyrazinamide in non-tuberculous mycobacterial (NTM) infections, expanding its potential utility.

Rifampin

The most widely used TB drug, rifampin, remains the focus of numerous clinical trials evaluating shorter, more effective regimens and combating resistance.

Significant recent efforts include NCT04672488, which assesses high-dose rifampin (35 mg/kg) to shorten treatment duration safely in drug-susceptible TB.^[3] The trial aims to improve cure rates and reduce treatment burden.

Another noteworthy study, NCT03158927, evaluates rifampin’s role in integrated HIV-TB therapy, crucial given co-infection prevalence. Researchers are also investigating novel formulations, such as long-acting injectables, to enhance adherence, especially in resource-limited settings.

Overall Clinical Trial Landscape

The Richard L. Smith COVID-19 pandemic disrupted some TB clinical activities but has spurred new approaches, including decentralized trials and digital adherence technologies. Major global institutions such as WHO and CDC continue advocating for accelerated development of TB therapeutics, including these three drugs, but the pipeline remains heavily focused on drug-resistant strains and shorter treatment durations.

Market Analysis

Market Size and Dynamics

The global anti-TB drugs market was valued at approximately $2.2 billion in 2022 and is projected to grow at a CAGR of 4-6% through 2030, driven by increasing TB prevalence and rising resistance issues.

Isoniazid retains dominance in first-line therapy but faces competition from generic versions and pipeline drugs targeting resistance. Its affordability and established efficacy sustain its market share, but newer formulations and resistant strain management efforts may alter this landscape.

Pyrazinamide benefits from its critical role in standard regimens; however, concerns over hepatotoxicity limit its widespread use, especially in multi-comorbid populations. The development of safer formulations and combination regimens could stimulate growth.

Rifampin commands the largest market share among these agents due to its versatility and central role in short-course therapies. The shift toward high-dose regimens and fixed-dose combinations (FDCs) aims to consolidate market positions, while interest in novel delivery systems could redefine competitive dynamics.

Regional Market Trends

• Emerging Markets (India, China, Africa): Dominant markets, fueled by high TB burdens, government-led procurement, and large generic manufacturing segments. The low-cost generics bolster accessibility but also intensify price competition.

• Developed Markets (U.S., Western Europe): Focus on drug-resistant TB, with specialty formulations and combination therapies. Market growth driven by clinical trial investments and regulatory approvals.

• Potential Market Disruptors: Novel drugs targeting MDR-TB, XDR-TB, and latent infection may supplement or replace traditional agents, impacting long-term revenues.

Key Market Players

Leading companies include Johnson & Johnson (Rifampin), GSK (Pyrazinamide), and Sanofi, involved in manufacturing, marketing, and research. Biotech firms and generic manufacturers are also expanding pipelines focused on resistance mitigation and formulation innovations.

Regulatory and Policy Influences

WHO's updated End TB strategy and GxP (Good Practice Pharmaceutical) initiatives shape procurement policies, emphasizing shorter, safer, and more effective regimens. Regulatory agencies (FDA, EMA) have progressively approved fixed-dose combinations, facilitating market expansion.

Market Projections and Future Outlook

Growth Drivers

• Rise in Multidrug-Resistant TB: Necessitates new combination regimens and bolsters demand for existing drugs, particularly rifampin and isoniazid.

• Global Health Initiatives: Increased funding from WHO, Global Fund, and domestic governments encourages innovation and access expansion.

• Development of Fixed-Dose and Novel Formulations: Improves adherence and treatment completions, especially in resource-limited settings.

Potential Challenges

• Resistance Development: Continuous emergence necessitates ongoing surveillance and novel drugs, possibly restricting the long-term relevance of current agents.

• Pricing Pressures: Patent expiries and generic competition could overwhelm branded sales, especially in low-income regions.

• Safety Concerns: Hepatotoxicity associated with pyrazinamide and isoniazid may limit usage or drive demand for safer alternatives or formulations.

Forecast Summary

By 2030, the global market for Isoniazid, Pyrazinamide, and Rifampin could reach $3.5–4.0 billion, assuming steady growth, increased adoption of new formulations, and ongoing TB control efforts. Rifampin is anticipated to lead growth, led by high-dose regimens and innovations in drug delivery, while isoniazid and pyrazinamide will remain essential but potentially supplemented by novel agents targeting resistance and safety.

Key Takeaways

• Existing clinical trials are refining dosing, safety, and combination strategies for these cornerstone TB agents, with significant attention to overcoming resistance.
• The global anti-TB market is poised for moderate growth, driven by rising resistance, development of new formulations, and international health initiatives.
• Rifampin currently dominates the market, with emerging high-dose and long-acting formulations expected to expand its role.
• Pyrazinamide’s future hinges on safety improvements and its expansion into new therapeutic areas such as NTM infections.
• Innovation in drug delivery, combination regimens, and resistance management will dictate the market trajectory over the coming decade.

FAQs

1. How are current clinical trials aiming to improve the efficacy of isoniazid?
Recent trials focus on optimizing dosing strategies for latent TB, reducing hepatotoxicity, and evaluating isoniazid in novel combination therapies to enhance efficacy against resistant strains.

2. What role does pyrazinamide play in managing drug-resistant TB?
While primarily part of first-line regimens, pyrazinamide’s role diminishes in resistant TB, but ongoing research aims to improve its safety profile and extend its utility in multidrug regimens.

3. Are high-dose rifampin regimens safe and effective?
Early-phase trials indicate high-dose rifampin can shorten therapy duration without significantly increasing adverse events, but further large-scale studies are ongoing to confirm safety and efficacy.

4. What market trends are influencing the development of new formulations for these drugs?
Demand for improved adherence, safety, and resistance management is propelling innovations like fixed-dose combinations, long-acting injectables, and safer formulations, especially in resource-constrained settings.

5. How might emerging resistance affect the future market for these drugs?
Growing MDR-TB and XDR-TB cases necessitate new drugs and combination regimens, potentially reducing reliance on traditional agents but also creating opportunities for innovative therapies.

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References

[1] World Health Organization. "Latent Tuberculosis Infection: Updated and Consolidated Guidelines for Programmatic Management." 2022.
[2] ClinicalTrials.gov. "Pyrazinamide Dose Optimization in TB Treatment." NCT03991261.
[3] ClinicalTrials.gov. "High-Dose Rifampin for TB." NCT04672488.