Rifapentine-Based Regimens for Latent Tuberculosis

(ASTERoiD Trial)

Recruiting at 23 trial locations

Overseen By TBTC Research Administrator

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Centers for Disease Control and Prevention

Must not be taking: Antiretrovirals, Contraindicated drugs

Disqualifiers: Current TB, Rifamycin resistance, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6-16 weeks

3400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new 6-week treatment for people with latent tuberculosis infection (LTBI) to determine if it matches the effectiveness and safety of the standard 12-16 week treatment. The goal is to shorten and potentially simplify treatment for those at high risk of developing active tuberculosis. Participants will take either the new 6-week daily rifapentine treatment (Priftin) or one of the current standard regimens. The trial seeks individuals who have been in close contact with someone with active TB, recently tested positive for TB infection, or have certain medical conditions that increase their risk of developing active TB. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on medications that cannot be taken with rifampin or rifapentine, you may not be eligible to participate. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that treatments using rifapentine for latent tuberculosis (TB) are generally well-tolerated. In one study with a similar treatment plan, where patients took rifapentine and isoniazid daily for one month, the treatment proved to be very safe. Most participants completed the treatment, and only a few experienced serious side effects. This suggests that rifapentine is safe for many people with latent TB.

For longer treatments lasting 12-16 weeks, which also use rifapentine, research indicates they are safe as well. Using rifapentine with isoniazid is strongly recommended for adults with latent TB, underscoring its safety.

While both treatment options are considered safe, participants should be monitored for any side effects. Always consult healthcare providers about any concerns before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for latent tuberculosis?

Researchers are excited about rifapentine-based regimens for latent tuberculosis because they offer a potentially shorter treatment duration compared to standard options. The 6-week daily rifapentine (6wP) regimen could significantly reduce treatment time from the typical 12-16 weeks required by current therapies like 3HP, 3HR, and 4R. This shorter regimen might improve patient compliance and completion rates, making it easier for people to stick to their treatment plan. Additionally, rifapentine is a potent antibiotic that could enhance the effectiveness of the treatment with possibly fewer side effects than longer regimens.

What evidence suggests that this trial's treatments could be effective for latent tuberculosis?

Research has shown that rifapentine effectively treats latent tuberculosis infection (LTBI). Studies have found that taking rifapentine with isoniazid for 3 months is as effective as taking isoniazid alone for 9 months in preventing active tuberculosis. This combination also results in higher treatment completion rates. Early research suggests that even shorter treatments, such as taking rifapentine daily for 6 weeks, might suffice to prevent the disease. In this trial, one group of participants will receive a 6-week daily rifapentine treatment to evaluate its effectiveness compared to the usual 12-16 week rifamycin-based regimens. Initial results indicate that rifapentine can reduce the risk of developing active TB with a shorter treatment duration. ^{6 7 8 9 10}

Who Is on the Research Team?

Timothy Sterling, MD

Principal Investigator

Vanderbilt University Medical Center, USA

Robert Belknap, MD

Principal Investigator

Denver Public Health (USA)

Amber Robinson, PhD

Principal Investigator

Centers for Disease Control and Prevention

Rosanna M Boyd, PhD

Principal Investigator

Centers for Disease Control (USA)

Dick Menzies, MD

Principal Investigator

McGill University

Are You a Good Fit for This Trial?

This trial is for people over 12 years old with latent TB infection at high risk of developing active TB, including recent immigrants from high-incidence countries and those in close contact with TB patients. Participants must not be pregnant or breastfeeding, agree to use contraception if applicable, have no history of TB treatment, and not be on certain conflicting medications.

Inclusion Criteria

I have lung scarring seen on an X-ray but have never been treated for TB.

I am HIV positive with a CD4 count over 100.

I agree to use contraception or abstain from sex during the study if I can have children and am not surgically sterilized.

Exclusion Criteria

I have been treated with rifamycin for more than 7 days or INH for more than 30 days within the last 2 years.

I am not on any medications that conflict with the study drugs.

I am not pregnant, breastfeeding, nor plan to become pregnant soon.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 6 weeks of daily rifapentine or 12-16 weeks of rifamycin-based treatment

6-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Rifapentine

Trial Overview The study compares a new short-term (6 weeks) daily treatment using Rifapentine against the standard longer-term (12-16 weeks) treatments for latent TB that include various combinations of Rifapentine, Isoniazid, and Rifampin. The goal is to see if the shorter regimen is just as safe and effective.

How Is the Trial Designed?

Group I: 6 weeks of daily rifapentine (6wP) Experimental Treatment 1 Intervention

Rifapentine daily for 6 weeks: 600 mg of Rifapentine (RPT) given once daily for 6 weeks

Group II: 12-16 week rifamycin-based regimen Active Control 3 Interventions

A 12-16 week rifamycin-based regimen available at the participant's site: "Rifapentine and Isoniazid weekly for 12 weeks" (3HP) or "Rifampin and Isoniazid daily for 12 weeks" (3HR) or "Rifampin daily for 16 weeks" (4R)

Rifapentine is already approved in United States, European Union for the following indications:

Approved in United States as Priftin for:

• Active tuberculosis
• Latent tuberculosis

Approved in European Union as Priftin for:

• Tuberculosis

Who Is Running the Clinical Trial?

Centers for Disease Control and Prevention

Lead Sponsor

Trials

902

Recruited

25,020,000+

British Medical Research Council

Collaborator

Trials

13

Recruited

2,127,000+

Published Research Related to This Trial

In a study of 399 household contacts of TB patients, the weekly treatment of rifapentine and isoniazid was found to be well tolerated, with significantly lower rates of hepatotoxicity (1%) compared to the daily rifampin and pyrazinamide regimen (10%).

Both treatments showed similar efficacy in preventing active TB, with slightly more cases in the rifapentine/isoniazid group, suggesting that rifapentine/isoniazid could be a promising alternative for latent TB infection therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly rifapentine/isoniazid or daily rifampin/pyrazinamide for latent tuberculosis in household contacts. Schechter, M., Zajdenverg, R., Falco, G., et al.[2022]

The once-weekly isoniazid and rifapentine (3H1P1) regimen for latent tuberculosis infection showed a higher treatment completion rate (92.9%) compared to the standard isoniazid plus rifampin (3HR) regimen (86.7%).

While the 3H1P1 group experienced more adverse events overall (75.2% vs 56.7%), it had significantly lower rates of hepatotoxicity (7.5% vs 20.0%) and no fatalities, although some cases of flu-like syndrome and anaphylaxis were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse event and treatment completion rates of a 12-dose weekly isoniazid and rifapentine course for South Korean healthcare workers. Jo, KW., Kim, JS., Kwon, HS., et al.[2020]

In an urban jail population, a 3-month treatment regimen of isoniazid and rifapentine (3HP) led to an impressive 85% completion rate for latent tuberculosis infection treatment, significantly higher than the 18% completion rate for the standard 9-month isoniazid treatment.

Only 2 out of 91 patients on the 3HP therapy discontinued treatment due to adverse drug reactions, indicating that this shorter regimen is not only more effective but also relatively safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Completion Rate and Side-Effect Profile of Three-Month Isoniazid and Rifapentine Treatment for Latent Tuberculosis Infection in an Urban County Jail. Juarez-Reyes, M., Gallivan, M., Chyorny, A., et al.[2020]

In a phase 3 trial with 2516 participants, a 4-month rifapentine regimen combined with moxifloxacin was found to be as effective as the standard 6-month treatment for drug-susceptible pulmonary tuberculosis, demonstrating noninferiority in preventing unfavorable outcomes.

The rifapentine-only regimen did not meet the noninferiority criteria compared to the standard treatment, indicating that moxifloxacin is crucial for maintaining efficacy in shorter treatment courses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis. Dorman, SE., Nahid, P., Kurbatova, EV., et al.[2022]

A Markov model analysis showed that both daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months are more cost-effective and effective than longer treatment options for latent tuberculosis infection (LTBI).

The daily regimen of isoniazid/rifapentine for one month was identified as the least expensive and most effective treatment option, suggesting it should be prioritized for further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential economic viability of two proposed rifapentine-based regimens for treatment of latent tuberculosis infection. Holland, DP., Sanders, GD., Hamilton, CD., et al.[2021]

Daily rifapentine-based regimens showed comparable efficacy to the standard rifampin+pyrazinamide regimen in treating latent tuberculosis infection (LTBI) in a mouse model, suggesting they could potentially shorten treatment duration to 6 to 8 weeks.

Existing regimens like isoniazid and rifampin were less effective, with many mice remaining culture-positive after 8 weeks, highlighting the improved effectiveness of rifapentine-based treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-course therapy with daily rifapentine in a murine model of latent tuberculosis infection. Zhang, T., Zhang, M., Rosenthal, IM., et al.[2021]

A 600-mg daily dose of rifapentine for 6 weeks (6wP) is predicted to be more effective in reducing bacterial loads in latent tuberculosis infection (LTBI) compared to the standard 3-month (3HP) and 1-month (1HP) regimens.

The study suggests that 6wP may achieve equal or better efficacy than 1HP and 3HP without the added toxicity associated with isoniazid, indicating a potentially safer treatment option for LTBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Efficacy of Rifapentine Alone and in Combination with Isoniazid for Latent Tuberculosis Infection: a Translational Pharmacokinetic-Pharmacodynamic Modeling Study. Radtke, KK., Ernest, JP., Zhang, N., et al.[2022]

In a study of 531 adults with pulmonary tuberculosis, rifapentine was found to be safe and showed similar efficacy to rifampin, with 86.4% of rifapentine patients achieving negative sputum cultures compared to 83.3% for rifampin after 8 weeks of treatment.

Both rifapentine and rifampin had similar rates of treatment discontinuation (15.7% for rifampin vs. 14.5% for rifapentine), indicating that rifapentine is a tolerable option for tuberculosis treatment, though further research on higher doses is suggested.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Substitution of rifapentine for rifampin during intensive phase treatment of pulmonary tuberculosis: study 29 of the tuberculosis trials consortium. Dorman, SE., Goldberg, S., Stout, JE., et al.[2015]

Rifapentine (RPT) and rifampicin (RMP) show similar efficacy and safety for treating pulmonary tuberculosis (PTB) in HIV-negative patients, based on a systematic review of nine randomized controlled trials.

However, using RPT once a week or less frequently increases the risk of bacteriological relapse compared to more frequent RMP dosing, and there are concerns that RPT may lead to rifamycin resistance in HIV-positive patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rifapentine vs. rifampicin for the treatment of pulmonary tuberculosis: a systematic review. Gao, XF., Li, J., Yang, ZW., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10533889/

Efficacy of anti-tuberculosis drugs for the treatment of latent ... Regarding the efficacy outcome, it was observed that 6H significantly reduced the risk of TB disease by 0.9% (RD − 0.009, 95% CI − 0.012, − ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12064123/

Prevalence and treatment outcomes of latent tuberculosis ... Efficacy and completion rates of rifapentine and isoniazid (3HP) compared to other treatment regimens for latent tuberculosis infection: a ...

3. cdc.gov cdc.gov/mmwr/volumes/69/rr/rr6901a1.htm

Guidelines for the Treatment of Latent Tuberculosis Infection The effectiveness outcome was tuberculosis disease; the toxicity outcome was hepatotoxicity. Strong GRADE recommendations required at least ...

4. pneumon.org pneumon.org/Efficacy-and-safety-rifapentine-containing-regimen-for-drug-sensitive-tuberculosis,186260,0,2.html

Efficacy and safety rifapentine-containing regimen for drug ... Preclinical research on mouse models has demonstrated that three months of daily rifapentine therapy is sufficient to cure patients. In ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1104875

Three Months of Rifapentine and Isoniazid for Latent ... The use of rifapentine plus isoniazid for 3 months was as effective as 9 months of isoniazid alone in preventing tuberculosis and had a higher treatment- ...

6. academic.oup.com academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaf404/8209960

Safety, Feasibility, and Rifapentine Plasma Concentration in ... The 1HP regimen (daily rifapentine/isoniazid for 1 month) demonstrated high safety and feasibility (98.75% completion; low rate of severe adverse events) i.

7. cdc.gov cdc.gov/tb/hcp/clinical-overview/latent-tuberculosis-infection.html

Clinical Overview of Latent Tuberculosis Infection Treating latent TB infection is 90% effective in preventing the development of TB disease. There are several standard treatment regimens for the ...

8. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2800774

Management of Latent Tuberculosis Infection Three months of weekly isoniazid and rifapentine is strongly recommended in all adults with LTBI. Compared with 9 months of isoniazid, weekly ...

9. products.sanofi.us products.sanofi.us/priftin/priftin.pdf

priftin.pdf Limitations of Use. Active tuberculosis disease should be ruled out before initiating treatment for latent tuberculosis infection. PRIFTIN must always be used ...

10. rsc.niaid.nih.gov rsc.niaid.nih.gov/clinical-research-sites/priftin-rifapentine-tablets-package-insert

Priftin (rifapentine) Tablets, Package Insert - daids rsc - NIH PRIFTIN is a rifamycin antimycobacterial drug indicated in patients 12 years of age and older for the treatment of active pulmonary tuberculosis (TB)