Video Based Directly Observed Therapy for Latent TB
| Status: | Recruiting |
|---|---|
| Conditions: | Infectious Disease |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 2/24/2019 |
| Start Date: | April 2019 |
| End Date: | June 30, 2020 |
| Contact: | Carol G Duane, RN, PhD |
| Email: | carol.duane@health.slu.edu |
| Phone: | 314-977-7536 |
Efficacy of Risk-Targeted Video Based Directly on Observed Therapy for Latent TB
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.
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.
Tuberculosis (TB) in the US: Tuberculosis (TB), caused by the bacterium Mycobacterium
tuberculosis (Mtb), is a leading cause of mortality, killing more than a million people
worldwide^1. In the United States an important recent trend has been the plateauing of the
active TB disease incidence at 3.0 cases per 100,000 persons^2. Current US TB control
guidelines recommend treating all subjects with LTBI to prevent progression to active TB.
However, treatment is given with the antibiotic Isoniazid (INH) for 6-9 months, Rifampin and
Rifabutin for 4 months or INH with Rifapentine for 3 months and as subjects with LTBI are
asymptomatic, treatment default rates are understandably high (>10% on average)^3-5. It is
well known that a subset of patients with LTBI have higher risk of progression to active TB.
Because of the high treatment default rate, a number of these "high risk" subjects receive
incomplete or no preventive therapy and contribute to the incidence of active TB cases in the
US. Currently, there are no strategies being implemented to identify those at highest risk
and consequently treatment approaches follow the "one size fits all" paradigm. In the
investigators preliminary study done at the Saint Louis University (SLU) Infectious Diseases
Clinic, the investigators used an online risk calculator (TSTin3D.com)^6 to retrospectively
determine the cumulative lifetime risk of progression to active TB for adults receiving
treatment for latent TB. The investigators found that current practice leads to equal rates
of treatment completion i.e. 57% in the high risk for active TB disease (TBhi) group (>10%
cumulative risk of progression based on medical risk factors) compared to 59% for those at
lowest risk (TBlow, <10% cumulative risk of progression). It is not standard of care to use a
scoring system like the TSTin3d.com to assess the risk. There are certain risk factors like
having HIV or being on immunosuppression that physicians ask about but most physicians do not
do a quantitative risk assessment. Treatment choices are usually based on convenience and
concern for side effects but the most common regimen is daily INH for 6-9 months.
This data implies that the current "treat everyone and hope that therapy is completed"
approach leads to a significant number of people in the TBhi group remaining untreated and at
high risk of progression to active TB. A recent advance has been a CDC approved regimen using
Isoniazid (INH) and Rifapentine given weekly as directly observed therapy (DOT) for 12 weeks
(known as the 3HP regimen). This regimen has shown lower toxicity, better adherence and
equivalent efficacy^7-12. INH + Rifapentine (3HP) is not currently used widely as DOT is
resource intensive. The investigators hypothesize that if providers use the calculator
(TSTin3d.com) to firstly determine risk and then select the once weekly DOT for the TBhi
group (12 doses total); the investigators can ensure that the TBhi group completes treatment.
Complete treatment of the TBhi group will have the highest impact in decreasing the community
burden of TB disease. The investigators propose the first US study to prospectively test the
efficacy of an approach which 1) defines the TBhi group using TSTin3d.com and 2) ensures
treatment completion in the TBhi group with weekly with video-based DOT (vDOT) with 3HP. Most
patients nowadays have access to a smartphone with video capabilities. A HIPAA approved video
application (Zoom) is already available through the Missouri Telehealth Network and can be
used by the patient to interface with the TB clinic nurse over a smartphone. The
investigators approach removes the need for the patients in the TBhi group to be physically
present in the TB clinic. All patients identified in the TBhi group can thus be safely
provided vDOT. The investigators pilot study has important implications for improving care
and patient treatment outcomes as it will identify the "high risk" subjects with latent TB
using tstin3d.com (Table 1), [a validated online calculator that combines TST or interferon
Gamma Release Assay (IGRA) screening results with clinical information obtained from the
patient, to generate an individual's cumulative risk of developing active TB disease, up to
age 80^11]. The investigators will then ensure that patients complete therapy under direct
observation by a nurse using video based Directly Observed Therapy (vDOT). vDOT also
eliminates the need for the patient to physically visit the clinic. All patients need is
access to a smartphone with video capabilities. HIPAA approved video based applications are
already available for vDOT and has already been implemented successfully.^13
All of the drug options listed are standard of care currently in the US. It is currently not
standard of care to use a scoring system like tstin3d.com to assess risk. There are certain
risk factors like having HIV or being on immunosuppression that physicians routinely ask
about but most physicians do not do a quantitative risk assessment. Treatment choices are
usually based on convenience and concern for side effects but the most common regimen is
daily INH for 6 months or 9 months.
tuberculosis (Mtb), is a leading cause of mortality, killing more than a million people
worldwide^1. In the United States an important recent trend has been the plateauing of the
active TB disease incidence at 3.0 cases per 100,000 persons^2. Current US TB control
guidelines recommend treating all subjects with LTBI to prevent progression to active TB.
However, treatment is given with the antibiotic Isoniazid (INH) for 6-9 months, Rifampin and
Rifabutin for 4 months or INH with Rifapentine for 3 months and as subjects with LTBI are
asymptomatic, treatment default rates are understandably high (>10% on average)^3-5. It is
well known that a subset of patients with LTBI have higher risk of progression to active TB.
Because of the high treatment default rate, a number of these "high risk" subjects receive
incomplete or no preventive therapy and contribute to the incidence of active TB cases in the
US. Currently, there are no strategies being implemented to identify those at highest risk
and consequently treatment approaches follow the "one size fits all" paradigm. In the
investigators preliminary study done at the Saint Louis University (SLU) Infectious Diseases
Clinic, the investigators used an online risk calculator (TSTin3D.com)^6 to retrospectively
determine the cumulative lifetime risk of progression to active TB for adults receiving
treatment for latent TB. The investigators found that current practice leads to equal rates
of treatment completion i.e. 57% in the high risk for active TB disease (TBhi) group (>10%
cumulative risk of progression based on medical risk factors) compared to 59% for those at
lowest risk (TBlow, <10% cumulative risk of progression). It is not standard of care to use a
scoring system like the TSTin3d.com to assess the risk. There are certain risk factors like
having HIV or being on immunosuppression that physicians ask about but most physicians do not
do a quantitative risk assessment. Treatment choices are usually based on convenience and
concern for side effects but the most common regimen is daily INH for 6-9 months.
This data implies that the current "treat everyone and hope that therapy is completed"
approach leads to a significant number of people in the TBhi group remaining untreated and at
high risk of progression to active TB. A recent advance has been a CDC approved regimen using
Isoniazid (INH) and Rifapentine given weekly as directly observed therapy (DOT) for 12 weeks
(known as the 3HP regimen). This regimen has shown lower toxicity, better adherence and
equivalent efficacy^7-12. INH + Rifapentine (3HP) is not currently used widely as DOT is
resource intensive. The investigators hypothesize that if providers use the calculator
(TSTin3d.com) to firstly determine risk and then select the once weekly DOT for the TBhi
group (12 doses total); the investigators can ensure that the TBhi group completes treatment.
Complete treatment of the TBhi group will have the highest impact in decreasing the community
burden of TB disease. The investigators propose the first US study to prospectively test the
efficacy of an approach which 1) defines the TBhi group using TSTin3d.com and 2) ensures
treatment completion in the TBhi group with weekly with video-based DOT (vDOT) with 3HP. Most
patients nowadays have access to a smartphone with video capabilities. A HIPAA approved video
application (Zoom) is already available through the Missouri Telehealth Network and can be
used by the patient to interface with the TB clinic nurse over a smartphone. The
investigators approach removes the need for the patients in the TBhi group to be physically
present in the TB clinic. All patients identified in the TBhi group can thus be safely
provided vDOT. The investigators pilot study has important implications for improving care
and patient treatment outcomes as it will identify the "high risk" subjects with latent TB
using tstin3d.com (Table 1), [a validated online calculator that combines TST or interferon
Gamma Release Assay (IGRA) screening results with clinical information obtained from the
patient, to generate an individual's cumulative risk of developing active TB disease, up to
age 80^11]. The investigators will then ensure that patients complete therapy under direct
observation by a nurse using video based Directly Observed Therapy (vDOT). vDOT also
eliminates the need for the patient to physically visit the clinic. All patients need is
access to a smartphone with video capabilities. HIPAA approved video based applications are
already available for vDOT and has already been implemented successfully.^13
All of the drug options listed are standard of care currently in the US. It is currently not
standard of care to use a scoring system like tstin3d.com to assess risk. There are certain
risk factors like having HIV or being on immunosuppression that physicians routinely ask
about but most physicians do not do a quantitative risk assessment. Treatment choices are
usually based on convenience and concern for side effects but the most common regimen is
daily INH for 6 months or 9 months.
Inclusion Criteria:
- 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).
Exclusion Criteria:
- 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
- Refuse blood draws
- Refuse to participate in the study
- If female of childbearing potential and on a hormonal contraception method, refuse to
use an additional barrier method with the hormonal method for the duration of the
study
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