Trial Outcomes & Findings for Using Biomarkers to Predict TB Treatment Duration (NCT NCT02821832)
NCT ID: NCT02821832
Last Updated: 2024-04-17
Results Overview
Estimation of the lower bound of a one-sided 95% confidence interval of the difference in success rates between arms B and C. If the lower bound is greater than -7%, this will be evidence that the treatment-shortening arm is not inferior to the standard duration arm.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
946 participants
Primary outcome timeframe
18 months
Results posted on
2024-04-17
Participant Flow
Participants were recruited from clinics in and around Cape Town, South Africa (RSA) and Henan Province, China. Recruitment in RSA began on 21Jun2017 and on 17Oct2017 in China. The final participant was recruited for this protocol on 31Mar2021.
Enrolled participants may have been excluded from participation for the following reasons: identification of baseline drug-resistant TB, withdrawn consent, sputum culture negative on Lowenstein-Jensen medium at baseline, poorly adherent to treatment, developed extrapulmonary TB, or had a significant incidental finding on baseline PET/CT requiring study withdrawal.
Participant milestones
| Measure |
Arm A
Expected high risk of relapse based on radiographic criteria, bacterial load criterion, and/or adherence criterion
standard of care treatment for 6 months: 2 months Isoniazid, Rifampicin, Pyrazinamide and Ethambutol + 4 months Isoniazid, Rifampicin
|
Arm B
Expected low risk of relapse based on radiographic criteria, bacterial load criterion, and/or adherence criterion
standard of care treatment for 6 months: 2 months Isoniazid, Rifampicin, Pyrazinamide and Ethambutol + 4 months Isoniazid, Rifampicin
|
Arm C
Expected low risk of relapse based on radiographic criteria, bacterial load criterion, and/or adherence criterion
shortened treatment: 2 months Isoniazid, Rifampicin, Pyrazinamide and Ethambutol + 2 months Isoniazid, Rifampicin
|
|---|---|---|---|
|
Overall Study
STARTED
|
251
|
154
|
141
|
|
Overall Study
COMPLETED
|
186
|
106
|
109
|
|
Overall Study
NOT COMPLETED
|
65
|
48
|
32
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Using Biomarkers to Predict TB Treatment Duration
Baseline characteristics by cohort
| Measure |
Arm A
n=251 Participants
Expected high risk of relapse based on radiographic criteria, bacterial load criterion, and/or adherence criterion standard of care treatment for 6 months: 2 months Isoniazid, Rifampicin, Pyrazinamide and Ethambutol + 4 months Isoniazid, Rifampicin
|
Arm B
n=154 Participants
Expected low risk of relapse based on radiographic criteria, bacterial load criterion, and/or adherence criterion standard of care treatment for 6 months: 2 months Isoniazid, Rifampicin, Pyrazinamide and Ethambutol + 4 months Isoniazid, Rifampicin
|
Arm C
n=141 Participants
Expected low risk of relapse based on radiographic criteria, bacterial load criterion, and/or adherence criterion shortened treatment: 2 months Isoniazid, Rifampicin, Pyrazinamide and Ethambutol + 2 months Isoniazid, Rifampicin
|
Total
n=546 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
37.5 years
n=5 Participants
|
35.5 years
n=7 Participants
|
33.4 years
n=5 Participants
|
35.8 years
n=4 Participants
|
|
Sex: Female, Male
Female
|
58 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
150 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
193 Participants
n=5 Participants
|
108 Participants
n=7 Participants
|
95 Participants
n=5 Participants
|
396 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
72 Participants
n=5 Participants
|
55 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
180 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
179 Participants
n=5 Participants
|
99 Participants
n=7 Participants
|
88 Participants
n=5 Participants
|
366 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
South Africa
|
179 participants
n=5 Participants
|
99 participants
n=7 Participants
|
88 participants
n=5 Participants
|
366 participants
n=4 Participants
|
|
Region of Enrollment
China
|
72 participants
n=5 Participants
|
55 participants
n=7 Participants
|
53 participants
n=5 Participants
|
180 participants
n=4 Participants
|
|
Weight
|
55.3 kilograms
STANDARD_DEVIATION 9.5 • n=5 Participants
|
55.0 kilograms
STANDARD_DEVIATION 9.7 • n=7 Participants
|
57.1 kilograms
STANDARD_DEVIATION 9.9 • n=5 Participants
|
55.7 kilograms
STANDARD_DEVIATION 9.7 • n=4 Participants
|
|
BMI
|
19.5 kg/m^2
STANDARD_DEVIATION 2.9 • n=5 Participants
|
19.7 kg/m^2
STANDARD_DEVIATION 2.8 • n=7 Participants
|
20.2 kg/m^2
STANDARD_DEVIATION 3.2 • n=5 Participants
|
19.7 kg/m^2
STANDARD_DEVIATION 3.0 • n=4 Participants
|
PRIMARY outcome
Timeframe: 18 monthsEstimation of the lower bound of a one-sided 95% confidence interval of the difference in success rates between arms B and C. If the lower bound is greater than -7%, this will be evidence that the treatment-shortening arm is not inferior to the standard duration arm.
Outcome measures
| Measure |
Arm A
n=237 Participants
Expected high risk of relapse based on radiographic criteria, bacterial load criterion, and/or adherence criterion
standard of care treatment for 6 months: 2 months Isoniazid, Rifampicin, Pyrazinamide and Ethambutol + 4 months Isoniazid, Rifampicin
|
Arm B
n=132 Participants
Expected low risk of relapse based on radiographic criteria, bacterial load criterion, and/or adherence criterion
standard of care treatment for 6 months: 2 months Isoniazid, Rifampicin, Pyrazinamide and Ethambutol + 4 months Isoniazid, Rifampicin
|
Arm C
n=139 Participants
Expected low risk of relapse based on radiographic criteria, bacterial load criterion, and/or adherence criterion
shortened treatment: 2 months Isoniazid, Rifampicin, Pyrazinamide and Ethambutol + 2 months Isoniazid, Rifampicin
|
|---|---|---|---|
|
Comparison of the Rate of Treatment Success at 18 Months (After Treatment Initiation) Between Arms B and C
Cured
|
217 Participants
|
121 Participants
|
117 Participants
|
|
Comparison of the Rate of Treatment Success at 18 Months (After Treatment Initiation) Between Arms B and C
Confirmed relapses
|
5 Participants
|
1 Participants
|
9 Participants
|
|
Comparison of the Rate of Treatment Success at 18 Months (After Treatment Initiation) Between Arms B and C
Late withdrawal, lost to follow-up
|
13 Participants
|
9 Participants
|
6 Participants
|
|
Comparison of the Rate of Treatment Success at 18 Months (After Treatment Initiation) Between Arms B and C
Probable relapses
|
1 Participants
|
1 Participants
|
3 Participants
|
|
Comparison of the Rate of Treatment Success at 18 Months (After Treatment Initiation) Between Arms B and C
Treatment Failure
|
1 Participants
|
0 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: 18 monthsThe difference (and 95% confidence interval) in treatment success rates between a combined A+B Arm (with Arm A participants selected to represent a true 6-month standard of care population) and a combined Arm A+C (with the remaining Arm A participants selected to represent a treatment shortening strategy arm, and no overlap in Arm A participants assigned to B and C).
Outcome measures
Outcome data not reported
Adverse Events
Arm A
Serious events: 20 serious events
Other events: 0 other events
Deaths: 4 deaths
Arm B
Serious events: 5 serious events
Other events: 0 other events
Deaths: 3 deaths
Arm C
Serious events: 3 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Arm A
n=251 participants at risk
Expected high risk of relapse based on radiographic criteria, bacterial load criterion, and/or adherence criterion
standard of care treatment for 6 months: 2 months Isoniazid, Rifampicin, Pyrazinamide and Ethambutol + 4 months Isoniazid, Rifampicin
|
Arm B
n=154 participants at risk
Expected low risk of relapse based on radiographic criteria, bacterial load criterion, and/or adherence criterion
standard of care treatment for 6 months: 2 months Isoniazid, Rifampicin, Pyrazinamide and Ethambutol + 4 months Isoniazid, Rifampicin
|
Arm C
n=141 participants at risk
Expected low risk of relapse based on radiographic criteria, bacterial load criterion, and/or adherence criterion
shortened treatment: 2 months Isoniazid, Rifampicin, Pyrazinamide and Ethambutol + 2 months Isoniazid, Rifampicin
|
|---|---|---|---|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
0.00%
0/251 • 72 weeks
|
0.00%
0/154 • 72 weeks
|
0.71%
1/141 • Number of events 1 • 72 weeks
|
|
Gastrointestinal disorders
Alcoholic pancreatitis
|
0.40%
1/251 • Number of events 1 • 72 weeks
|
0.00%
0/154 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
Injury, poisoning and procedural complications
Animal bite
|
0.40%
1/251 • Number of events 1 • 72 weeks
|
0.00%
0/154 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
Gastrointestinal disorders
Appendicitis
|
0.40%
1/251 • Number of events 1 • 72 weeks
|
0.00%
0/154 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
Vascular disorders
Arteriosclerosis
|
0.00%
0/251 • 72 weeks
|
0.65%
1/154 • Number of events 1 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
Reproductive system and breast disorders
Bartholin's cyst
|
0.40%
1/251 • Number of events 1 • 72 weeks
|
0.00%
0/154 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.00%
0/251 • 72 weeks
|
0.00%
0/154 • 72 weeks
|
0.71%
1/141 • Number of events 1 • 72 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.40%
1/251 • Number of events 2 • 72 weeks
|
0.00%
0/154 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease
|
0.40%
1/251 • Number of events 1 • 72 weeks
|
0.00%
0/154 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
Cardiac disorders
Cor pulmonale
|
0.40%
1/251 • Number of events 1 • 72 weeks
|
0.00%
0/154 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
Infections and infestations
Coronavirus infection
|
0.00%
0/251 • 72 weeks
|
0.65%
1/154 • Number of events 1 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
General disorders
Death
|
0.40%
1/251 • Number of events 1 • 72 weeks
|
0.00%
0/154 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
Vascular disorders
Deep vein thrombosis
|
0.40%
1/251 • Number of events 1 • 72 weeks
|
0.00%
0/154 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
Pregnancy, puerperium and perinatal conditions
Foetal death
|
0.40%
1/251 • Number of events 1 • 72 weeks
|
0.00%
0/154 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
Infections and infestations
Gangrene
|
0.00%
0/251 • 72 weeks
|
0.65%
1/154 • Number of events 1 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
Injury, poisoning and procedural complications
Gunshot wound
|
0.40%
1/251 • Number of events 1 • 72 weeks
|
0.00%
0/154 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
Vascular disorders
Haematoma
|
0.40%
1/251 • Number of events 1 • 72 weeks
|
0.00%
0/154 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Haemothorax
|
0.40%
1/251 • Number of events 1 • 72 weeks
|
0.00%
0/154 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
Injury, poisoning and procedural complications
Head trauma
|
0.00%
0/251 • 72 weeks
|
0.65%
1/154 • Number of events 1 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.40%
1/251 • Number of events 1 • 72 weeks
|
0.00%
0/154 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
Vascular disorders
Hypertension
|
0.40%
1/251 • Number of events 1 • 72 weeks
|
0.00%
0/154 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
Surgical and medical procedures
Leg amputation
|
0.00%
0/251 • 72 weeks
|
0.65%
1/154 • Number of events 1 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-small cell lung cancer
|
0.40%
1/251 • Number of events 2 • 72 weeks
|
0.00%
0/154 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/251 • 72 weeks
|
0.65%
1/154 • Number of events 1 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
Infections and infestations
Pneumonia
|
0.00%
0/251 • 72 weeks
|
0.00%
0/154 • 72 weeks
|
0.71%
1/141 • Number of events 1 • 72 weeks
|
|
Injury, poisoning and procedural complications
Pneumothorax traumatic
|
0.40%
1/251 • Number of events 1 • 72 weeks
|
0.00%
0/154 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
General disorders
Pyrexia
|
0.00%
0/251 • 72 weeks
|
0.00%
0/154 • 72 weeks
|
0.71%
1/141 • Number of events 1 • 72 weeks
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.40%
1/251 • Number of events 1 • 72 weeks
|
0.00%
0/154 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
Injury, poisoning and procedural complications
Stab wound
|
1.2%
3/251 • Number of events 3 • 72 weeks
|
0.65%
1/154 • Number of events 2 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
Pregnancy, puerperium and perinatal conditions
Stillbirth
|
0.40%
1/251 • Number of events 1 • 72 weeks
|
0.00%
0/154 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
|
Injury, poisoning and procedural complications
Urethral injury
|
0.00%
0/251 • 72 weeks
|
0.65%
1/154 • Number of events 1 • 72 weeks
|
0.00%
0/141 • 72 weeks
|
Other adverse events
Adverse event data not reported
Additional Information
Dr. Clif E. Barry 3rd
National Institute of Allergy and Infectious Diseases
Phone: 301-693-4665
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place