Tuberculosis Infections and Infestations
Conditions
Interventions
Study design: 920 participants will be randomized with allocation ratio 5:5:6:6:6:6 to one of the following arms:
ARM 1- Daily isoniazid plus rifampicin (<50 kg = 150/100 mg fixed dose oral tablet, =
Sponsors
University College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged > = 16 years to = 40 cases/100,000 population); or 3.3. Individuals who are assessed in the TB clinic for latent TB testing, or have been referred for treatment following testing by specialities or departments within primary or secondary care settings 4. Agree to LTBI treatment 5. Willing and able to provide written informed consent
Exclusion criteria
Exclusion criteria: 1. Patients weighing < 30 kg. 2. Need for medications that cannot be safely taken together with study drugs 3. Any medical condition deserving priority of treatment (such as: porphyria, malabsorption syndromes, Clostridium difficile-associated diarrhoea and other conditions) 4. History of sensitivity/intolerance to isoniazid or rifamycins 5. Individuals with documented liver disease, defined as: 5.1. LFT (ALT/AST/bilirubin) over three times upper limit of normal (ULN) at baseline. This reflects normal clinical practice. For patient participant safety, liver function tests are carried on a regular basis. One abnormal value prevents the patient from participating on the study. 5.2. Clinical diagnosis of cirrhosis (jaundice, hematemesis, ascites or previous episodes of liver encephalopathy), 5.3. HbsAg positive or HCV antibody positive and deemed ineligible for LTBI treatment by the clinician 6. Intending to move outside of the treatment locality within 20 weeks of starting treatment 7. Individuals who would usually be offered LTBI treatment under Directly Observed Therapy (DOT) as part of enhanced case management in complex cases such as those from under-served groups (such as people who are homeless, misuse substances, have been in prison or who are vulnerable migrants). 8. Use of another experimental investigational medicinal product that is likely to interfere with the study medication within 3 months of study enrolment. 9. Women who are breastfeeding, pregnant, or of childbearing potential* who do not agree to use an effective method of contraception from the time consent is signed until 4 weeks after treatment discontinuation or completion. 10. Women of childbearing potential without a negative urine pregnancy test within 7 days prior to being registered for trial treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adequate treatment adherence is defined as taking =90% of allotted doses within the allowable time frame specified by the treatment plan. Time-frames differ depending on the treatment arm that a participant is randomized to. 3HR and 3HP arms (i.e. arms 1, 2, 3, 4) have 16 weeks to complete, and the 1HP arm (i.e. arm 5) has 8 weeks to complete. Adherence data is checked at all follow-up visits. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Proportion of doses missed over the treatment period measured using a dose count, self-reporting, and Wisepill monitoring box at weeks 2, 4, 8, 12, 16, and 20. 2. Proportion of pills missed over the treatment period measured using a pill count, self-reporting, and Wisepill monitoring box at weeks 2, 4, 8, 12, 16, and 20. 3. Taking at least 90% of doses and pills over the treatment period measured using a dose and a pill count, self-reporting, and Wisepill monitoring box at weeks 2, 4, 8, 12, 16, and 20. 4. Early study treatment discontinuation for any reason measured using participant status data collection at weeks 2, 4, 8, 12, 16, and 20. 5. Permanently stopping study treatment due to drug-related adverse events, measured using adverse event data collection at weeks 2, 4, 8, 12, 16, and 20. 6. Grade =3 adverse events, measured using adverse event data collection at weeks 2, 4, 8, 12, 16, and 20. 7. Adverse events at least possibly associated with study treatment, measured using adverse event data collection at weeks 2, 4, 8, 12, 16, and 20. 8. Development of active TB within 12 months of starting treatment, measured by assessing TB symptoms at weeks 2, 4, 8, 12, 16, and 20 and using records held by NHS Digital, Public Health England, and/or the National TB register at week 52. | — |
Countries
England, United Kingdom
Outcome results
None listed