Trial Outcomes & Findings for Trial of High-Dose Rifampin in Patients With TB (NCT NCT01408914)
NCT ID: NCT01408914
Last Updated: 2017-11-20
Results Overview
The endpoint is the (dimensionless) ratio of AUC0-6 mcg/ml\*h to MIC99.9 mcg/ml
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
180 participants
Primary outcome timeframe
At any time during the intensive phase of treatment, after steady state has been reached (at a minimum, after 14 days of daily RIF delivery)
Results posted on
2017-11-20
Participant Flow
Recruitment was done through routine passive case detection in operation at ambulatory facilities in the Peruvian public health system (DISA IV-Lima Este and DISA V- Lima Ciudad).
180 participants were randomized in a 1:1:1 allocation to the 10, 15, and 20 mg/kg treatment arms.
Participant milestones
| Measure |
10 mg/kg
10 mg/kg RIF
|
15 mg/kg
15 mg/kg RIF
|
20 mg/kg
20 mg/kg RIF
|
|---|---|---|---|
|
Overall Study
STARTED
|
60
|
60
|
60
|
|
Overall Study
COMPLETED
|
48
|
48
|
47
|
|
Overall Study
NOT COMPLETED
|
12
|
12
|
13
|
Reasons for withdrawal
| Measure |
10 mg/kg
10 mg/kg RIF
|
15 mg/kg
15 mg/kg RIF
|
20 mg/kg
20 mg/kg RIF
|
|---|---|---|---|
|
Overall Study
Could not complete tx in protocol period
|
5
|
5
|
6
|
|
Overall Study
Lost to Follow-up
|
4
|
1
|
2
|
|
Overall Study
Physician Decision
|
1
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
1
|
|
Overall Study
Moved out of study jurisdiction
|
1
|
1
|
0
|
|
Overall Study
Late exclusion
|
0
|
3
|
3
|
|
Overall Study
Change in local TB/HIV norms
|
0
|
1
|
1
|
Baseline Characteristics
Trial of High-Dose Rifampin in Patients With TB
Baseline characteristics by cohort
| Measure |
10 mg/kg
n=60 Participants
10 mg/kg RIF
|
15 mg/kg
n=60 Participants
15 mg/kg RIF
|
20 mg/kg
n=60 Participants
20 mg/kg RIF
|
Total
n=180 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
24 years
n=5 Participants
|
25 years
n=7 Participants
|
27 years
n=5 Participants
|
25 years
n=4 Participants
|
|
Sex: Female, Male
Female
|
21 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
66 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
39 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
114 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
60 Participants
n=5 Participants
|
60 Participants
n=7 Participants
|
59 Participants
n=5 Participants
|
179 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Ethnicity (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
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
57 Participants
n=5 Participants
|
51 Participants
n=7 Participants
|
54 Participants
n=5 Participants
|
162 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: At any time during the intensive phase of treatment, after steady state has been reached (at a minimum, after 14 days of daily RIF delivery)Population: Analysis was completed in 168 participants evaluable for pharmacokinetics, as samples were unable to be collected in 12 study participants.
The endpoint is the (dimensionless) ratio of AUC0-6 mcg/ml\*h to MIC99.9 mcg/ml
Outcome measures
| Measure |
10 mg/kg
n=58 Participants
10 mg/kg RIF
|
15 mg/kg
n=57 Participants
15 mg/kg RIF
|
20 mg/kg
n=53 Participants
20 mg/kg RIF
|
|---|---|---|---|
|
Steady State Pharmacokinetic Exposure of RIF
|
115.6988 Ratio
Interval 59.1233 to 197.5544
|
201.9725 Ratio
Interval 144.1413 to 460.2869
|
284.4278 Ratio
Interval 175.2923 to 399.2127
|
SECONDARY outcome
Timeframe: Until 8 weeks of treatment are completedNumber of participants that are sputum culture (in LJ) negative for TB at 8 weeks
Outcome measures
| Measure |
10 mg/kg
n=60 Participants
10 mg/kg RIF
|
15 mg/kg
n=60 Participants
15 mg/kg RIF
|
20 mg/kg
n=60 Participants
20 mg/kg RIF
|
|---|---|---|---|
|
Sputum Culture Sterilization During the Initial 8 Weeks of Treatment
|
46 Participants
|
44 Participants
|
45 Participants
|
SECONDARY outcome
Timeframe: Throughout the 12 weeks post treatment initiationNumber of participants experiencing at least one rifampin-related grade 2 or higher adverse events during the initial 8 weeks of treatment and up to four weeks after.
Outcome measures
| Measure |
10 mg/kg
n=60 Participants
10 mg/kg RIF
|
15 mg/kg
n=60 Participants
15 mg/kg RIF
|
20 mg/kg
n=60 Participants
20 mg/kg RIF
|
|---|---|---|---|
|
Incidence of Rifampin-related Grade 2 or Higher Adverse Events
|
26 Participants
|
31 Participants
|
23 Participants
|
Adverse Events
10 mg/kg
Serious events: 2 serious events
Other events: 26 other events
Deaths: 0 deaths
15 mg/kg
Serious events: 1 serious events
Other events: 30 other events
Deaths: 0 deaths
20 mg/kg
Serious events: 5 serious events
Other events: 21 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
10 mg/kg
n=60 participants at risk
10 mg/kg RIF
|
15 mg/kg
n=60 participants at risk
15 mg/kg RIF
|
20 mg/kg
n=60 participants at risk
20 mg/kg RIF
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Respiratory
|
1.7%
1/60 • Number of events 1
|
0.00%
0/60
|
3.3%
2/60 • Number of events 2
|
|
Hepatobiliary disorders
Hepatic
|
1.7%
1/60 • Number of events 1
|
1.7%
1/60 • Number of events 1
|
3.3%
2/60 • Number of events 2
|
|
Ear and labyrinth disorders
Neurological
|
0.00%
0/60
|
0.00%
0/60
|
1.7%
1/60 • Number of events 1
|
|
Pregnancy, puerperium and perinatal conditions
OB-GYN
|
0.00%
0/60
|
0.00%
0/60
|
1.7%
1/60 • Number of events 1
|
Other adverse events
| Measure |
10 mg/kg
n=60 participants at risk
10 mg/kg RIF
|
15 mg/kg
n=60 participants at risk
15 mg/kg RIF
|
20 mg/kg
n=60 participants at risk
20 mg/kg RIF
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders
|
1.7%
1/60 • Number of events 1
|
1.7%
1/60 • Number of events 1
|
1.7%
1/60 • Number of events 1
|
|
Gastrointestinal disorders
Gastrointestinal disorders
|
6.7%
4/60 • Number of events 4
|
21.7%
13/60 • Number of events 15
|
6.7%
4/60 • Number of events 5
|
|
Hepatobiliary disorders
Hepatobiliary disorders
|
26.7%
16/60 • Number of events 16
|
21.7%
13/60 • Number of events 13
|
20.0%
12/60 • Number of events 12
|
|
Immune system disorders
Immune system disorders
|
0.00%
0/60
|
0.00%
0/60
|
1.7%
1/60 • Number of events 1
|
|
Investigations
Investigations
|
1.7%
1/60 • Number of events 1
|
1.7%
1/60 • Number of events 1
|
0.00%
0/60
|
|
Metabolism and nutrition disorders
Metabolism and Nutrition Disorders
|
0.00%
0/60
|
1.7%
1/60 • Number of events 1
|
0.00%
0/60
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders
|
3.3%
2/60 • Number of events 2
|
5.0%
3/60 • Number of events 3
|
5.0%
3/60 • Number of events 3
|
|
Nervous system disorders
Nervous system disorder
|
1.7%
1/60 • Number of events 1
|
1.7%
1/60 • Number of events 1
|
0.00%
0/60
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders
|
0.00%
0/60
|
5.0%
3/60 • Number of events 3
|
1.7%
1/60 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders
|
10.0%
6/60 • Number of events 6
|
1.7%
1/60 • Number of events 1
|
11.7%
7/60 • Number of events 8
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place