Video Based Directly Observed Therapy for Latent TB

NCT03783728 | Withdrawn FDA Drug

• 1 other identifier: 29312
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Center for Disease Control (CDC) data reveal that after years of sustained decrease, the incidence of active tuberculosis (TB) disease in the US has plateaued. Most of the cases occur when Mycobacterium tuberculosis (Mtb) reactivates replication in people who have latent tuberculosis infection (LTBI). Only 5 to 10% of subjects with LTBI develop active TB Infection over their lifetime. Current US guidelines recommend treating everyone with LTBI to stop progression to active TB. As treatment is long, only about 45-55% of patients finish treatment overall, regardless of whether the patients are at high (\>10%) or low lifetime risk of reactivation. The investigator's study aims to test the efficacy of a combined approach of first determining subjects at high risk of reactivation and then treating them with a CDC approved once a week treatment regimen, directly observed by a nurse over video (video-based Directly Observed Therapy, vDOT). Ensuring treatment of the high-risk group will eventually decrease the community active TB burden.

Conditions

Latent Tuberculosis

Outcome Measures

Primary Outcomes (1)

• Percentage of patients completing treatment

  Achieving \> 90% treatment completion in patients with LTBI at \> 10% cumulative individual risk of developing active TB using vDOT.

  4 months

Study Arms (1)

Untreated Latent Tuberculosis Infection

Isoniazid 900 mg orally + Rifapentine 600 mg orally + Pyridoxine 50 mg orally once a week for 12 weeks

Drug: Rifapentine 600 mg orally; Drug: Isoniazid 900 mg orally; Drug: Pyridoxine 50 mg orally

Interventions

Rifapentine 600 mg orally DRUG

Once a week for 12 weeks using Video Directly Observed Therapy

Also known as: Priftin

Untreated Latent Tuberculosis Infection

Isoniazid 900 mg orally DRUG

Once a week for 12 weeks using Video Directly Observed Therapy

Also known as: INH

Untreated Latent Tuberculosis Infection

Pyridoxine 50 mg orally DRUG

Once a week for 12 weeks using Video Directly Observed Therapy

Also known as: Vitamin B6

Untreated Latent Tuberculosis Infection

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults with latent tuberculosis

You may qualify if:

• \- Age 18 years + 1 day (defined as date of birth plus one day). This age cutoff has been selected as tstin3d.com has only been validated for this age group.
• Subjects must have all of the following:
• Untreated Latent Tuberculosis Infection (LTBI), defined as positive Tuberculin skin test/QuantiFERON TB Gold test or T-spot assay done within 1 month prior to enrollment.
• Absence of active TB disease as determined by history, physical examination, chest X-ray, (sputum smear and/or culture done as needed by the assessing physician for Mtb).
• Greater than 10% cumulative risk of developing active TB disease (determined by TSTin3D.com).

You may not qualify if:

• A subject will be excluded if any of the following criteria are met:
• Presence of active TB disease
• BMI \<16
• Cardiovascular instability (Blood pressure: Systolic \>180 or \<90 mm/Hg or Diastolic \>100 or \< 50mm/Hg; pulse \<40 or \>110)
• Chest X-Ray report within last 3 months not available
• HIV positive and currently on treatment with a regimen that has severe drug interactions with 3HP.
• Presumed infected with INH or Rifapentine (RIF)-resistant M. tuberculosis
• Women who are pregnant, nursing or expect to become pregnant for the duration of the study.
• Temperature ≥38.5°C or other clinical evidence of an acute infection at screening
• History of treatment for \>14 consecutive days with a rifamycin or \>30 consecutive days with isoniazid during the previous 2 years
• Documented history of completing adequate treatment for active tuberculosis or latent M. tuberculosis infection in a HIV-seronegative person
• History of sensitivity/intolerance to isoniazid or rifamycins
• Serum aspartate aminotransferase (AST) \>5 times the upper limit of normal (ULN) if AST was determined
• Hemodynamic instability or medical/psychological condition precluding participation in the study as judged by the investigator
• No access to a smartphone for personal use

Sponsors & Collaborators

• St. Louis University: lead

Study Sites (1)

Saint Louis University

St Louis, Missouri, 63104, United States

Location

Related Publications (9)

• Salinas JL, Mindra G, Haddad MB, Pratt R, Price SF, Langer AJ. Leveling of Tuberculosis Incidence - United States, 2013-2015. MMWR Morb Mortal Wkly Rep. 2016 Mar 25;65(11):273-8. doi: 10.15585/mmwr.mm6511a2.

  PMID: 27010173 RESULT

• Li J, Munsiff SS, Tarantino T, Dorsinville M. Adherence to treatment of latent tuberculosis infection in a clinical population in New York City. Int J Infect Dis. 2010 Apr;14(4):e292-7. doi: 10.1016/j.ijid.2009.05.007. Epub 2009 Aug 4.

  PMID: 19656705 RESULT

• Stuurman AL, Vonk Noordegraaf-Schouten M, van Kessel F, Oordt-Speets AM, Sandgren A, van der Werf MJ. Interventions for improving adherence to treatment for latent tuberculosis infection: a systematic review. BMC Infect Dis. 2016 Jun 8;16:257. doi: 10.1186/s12879-016-1549-4.

  PMID: 27268103 RESULT

• Sterling TR, Scott NA, Miro JM, Calvet G, La Rosa A, Infante R, Chen MP, Benator DA, Gordin F, Benson CA, Chaisson RE, Villarino ME; Tuberculosis Trials Consortium, the AIDS Clinical Trials Group for the PREVENT TB Trial (TBTC Study 26ACTG 5259) The investigators of the TB Trials Consortium and the AIDS Clinical Trials Group for the PREVENT TB Trial are listed in the Supplement, item 17. Three months of weekly rifapentine and isoniazid for treatment of Mycobacterium tuberculosis infection in HIV-coinfected persons. AIDS. 2016 Jun 19;30(10):1607-15. doi: 10.1097/QAD.0000000000001098.

  PMID: 27243774 RESULT

• Sterling TR, Moro RN, Borisov AS, Phillips E, Shepherd G, Adkinson NF, Weis S, Ho C, Villarino ME; Tuberculosis Trials Consortium. Flu-like and Other Systemic Drug Reactions Among Persons Receiving Weekly Rifapentine Plus Isoniazid or Daily Isoniazid for Treatment of Latent Tuberculosis Infection in the PREVENT Tuberculosis Study. Clin Infect Dis. 2015 Aug 15;61(4):527-35. doi: 10.1093/cid/civ323. Epub 2015 Apr 22.

  PMID: 25904367 RESULT

• Bliven-Sizemore EE, Sterling TR, Shang N, Benator D, Schwartzman K, Reves R, Drobeniuc J, Bock N, Villarino ME; TB Trials Consortium. Three months of weekly rifapentine plus isoniazid is less hepatotoxic than nine months of daily isoniazid for LTBI. Int J Tuberc Lung Dis. 2015 Sep;19(9):1039-44, i-v. doi: 10.5588/ijtld.14.0829.

  PMID: 26260821 RESULT

• Sterling TR, Villarino ME, Borisov AS, Shang N, Gordin F, Bliven-Sizemore E, Hackman J, Hamilton CD, Menzies D, Kerrigan A, Weis SE, Weiner M, Wing D, Conde MB, Bozeman L, Horsburgh CR Jr, Chaisson RE; TB Trials Consortium PREVENT TB Study Team. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med. 2011 Dec 8;365(23):2155-66. doi: 10.1056/NEJMoa1104875.

  PMID: 22150035 RESULT

• Holzschuh EL, Province S, Johnson K, Walls C, Shemwell C, Martin G, Showalter A, Dunlay J, Conyers A, Griffin P, Tausz N. Use of Video Directly Observed Therapy for Treatment of Latent Tuberculosis Infection - Johnson County, Kansas, 2015. MMWR Morb Mortal Wkly Rep. 2017 Apr 14;66(14):387-389. doi: 10.15585/mmwr.mm6614a3.

  PMID: 28406884 RESULT

• Menzies D, Gardiner G, Farhat M, Greenaway C, Pai M. Thinking in three dimensions: a web-based algorithm to aid the interpretation of tuberculin skin test results. Int J Tuberc Lung Dis. 2008 May;12(5):498-505.

  PMID: 18419884 RESULT

Related Links

• World Health Organization (WHO) TB Report

Biospecimen

Retention: SAMPLES WITHOUT DNA

20 mL of Peripheral Blood Mononuclear Cells (PBMCs) will be collected for future research.

MeSH Terms

Conditions

Latent Tuberculosis

Interventions

rifapentine; Isoniazid; Pyridoxine; Vitamin B 6

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection

Intervention Hierarchy (Ancestors)

Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Picolines

Study Officials

• Soumya Chatterjee, MD

  St. Louis University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Internal Medicine

Study Record Dates

• First Submitted: December 19, 2018
• First Posted: December 21, 2018
• Study Start: June 30, 2019
• Primary Completion: January 31, 2020
• Study Completion: January 31, 2020
• Last Updated: July 1, 2019

Record last verified: 2019-06

Locations

US (1)