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Trial record 1 of 1 for:    NCT01408914
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Trial of High-Dose Rifampin in Patients With TB (HIRIF)

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ClinicalTrials.gov Identifier: NCT01408914
Recruitment Status : Completed
First Posted : August 3, 2011
Results First Posted : July 13, 2017
Last Update Posted : November 20, 2017
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
Sanofi
Harvard School of Public Health
Brigham and Women's Hospital
University of Liverpool
St George's, University of London
University of Florida
Socios en Salud
Information provided by (Responsible Party):
Carole Mitnick, Harvard University Faculty of Medicine

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Outcomes Assessor);   Primary Purpose: Treatment
Condition Tuberculosis
Intervention Drug: Higher-Dose Rifampin
Enrollment 180
Recruitment Details 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).
Pre-assignment Details 180 participants were randomized in a 1:1:1 allocation to the 10, 15, and 20 mg/kg treatment arms.
Arm/Group Title 10 mg/kg 15 mg/kg 20 mg/kg
Hide Arm/Group Description 10 mg/kg RIF 15 mg/kg RIF 20 mg/kg RIF
Period Title: Overall Study
Started 60 60 60
Completed 48 48 47
Not Completed 12 12 13
Reason Not Completed
Could not complete tx in protocol period             5             5             6
Lost to Follow-up             4             1             2
Physician Decision             1             1             0
Withdrawal by Subject             1             0             1
Moved out of study jurisdiction             1             1             0
Late exclusion             0             3             3
Change in local TB/HIV norms             0             1             1
Arm/Group Title 10 mg/kg 15 mg/kg 20 mg/kg Total
Hide Arm/Group Description 10 mg/kg RIF 15 mg/kg RIF 20 mg/kg RIF Total of all reporting groups
Overall Number of Baseline Participants 60 60 60 180
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 60 participants 60 participants 60 participants 180 participants
24
(21 to 37)
25
(20 to 35)
27
(22 to 37)
25
(21 to 37)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 60 participants 60 participants 60 participants 180 participants
Female
21
  35.0%
19
  31.7%
26
  43.3%
66
  36.7%
Male
39
  65.0%
41
  68.3%
34
  56.7%
114
  63.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 60 participants 60 participants 60 participants 180 participants
Hispanic or Latino
60
 100.0%
60
 100.0%
59
  98.3%
179
  99.4%
Not Hispanic or Latino
0
   0.0%
0
   0.0%
1
   1.7%
1
   0.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 60 participants 60 participants 60 participants 180 participants
American Indian or Alaska Native
1
   1.7%
1
   1.7%
1
   1.7%
3
   1.7%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
0
   0.0%
2
   3.3%
1
   1.7%
3
   1.7%
More than one race
57
  95.0%
51
  85.0%
54
  90.0%
162
  90.0%
Unknown or Not Reported
2
   3.3%
6
  10.0%
4
   6.7%
12
   6.7%
1.Primary Outcome
Title Steady State Pharmacokinetic Exposure of RIF
Hide Description The endpoint is the (dimensionless) ratio of AUC0-6 mcg/ml*h to MIC99.9 mcg/ml
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was completed in 168 participants evaluable for pharmacokinetics, as samples were unable to be collected in 12 study participants.
Arm/Group Title 10 mg/kg 15 mg/kg 20 mg/kg
Hide Arm/Group Description:
10 mg/kg RIF
15 mg/kg RIF
20 mg/kg RIF
Overall Number of Participants Analyzed 58 57 53
Median (Inter-Quartile Range)
Unit of Measure: Ratio
115.6988
(59.1233 to 197.5544)
201.9725
(144.1413 to 460.2869)
284.4278
(175.2923 to 399.2127)
2.Secondary Outcome
Title Sputum Culture Sterilization During the Initial 8 Weeks of Treatment
Hide Description Number of participants that are sputum culture (in LJ) negative for TB at 8 weeks
Time Frame Until 8 weeks of treatment are completed
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 10 mg/kg 15 mg/kg 20 mg/kg
Hide Arm/Group Description:
10 mg/kg RIF
15 mg/kg RIF
20 mg/kg RIF
Overall Number of Participants Analyzed 60 60 60
Measure Type: Count of Participants
Unit of Measure: Participants
46
  76.7%
44
  73.3%
45
  75.0%
3.Secondary Outcome
Title Incidence of Rifampin-related Grade 2 or Higher Adverse Events
Hide Description Number 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.
Time Frame Throughout the 12 weeks post treatment initiation
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 10 mg/kg 15 mg/kg 20 mg/kg
Hide Arm/Group Description:
10 mg/kg RIF
15 mg/kg RIF
20 mg/kg RIF
Overall Number of Participants Analyzed 60 60 60
Measure Type: Count of Participants
Unit of Measure: Participants
26
  43.3%
31
  51.7%
23
  38.3%
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 10 mg/kg 15 mg/kg 20 mg/kg
Hide Arm/Group Description 10 mg/kg RIF 15 mg/kg RIF 20 mg/kg RIF
All-Cause Mortality
10 mg/kg 15 mg/kg 20 mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Hide Serious Adverse Events
10 mg/kg 15 mg/kg 20 mg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/60 (3.33%)      1/60 (1.67%)      5/60 (8.33%)    
Ear and labyrinth disorders       
Neurological  0/60 (0.00%)  0 0/60 (0.00%)  0 1/60 (1.67%)  1
Hepatobiliary disorders       
Hepatic  1/60 (1.67%)  1 1/60 (1.67%)  1 2/60 (3.33%)  2
Pregnancy, puerperium and perinatal conditions       
OB-GYN  0/60 (0.00%)  0 0/60 (0.00%)  0 1/60 (1.67%)  1
Respiratory, thoracic and mediastinal disorders       
Respiratory  1/60 (1.67%)  1 0/60 (0.00%)  0 2/60 (3.33%)  2
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
10 mg/kg 15 mg/kg 20 mg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   26/60 (43.33%)      30/60 (50.00%)      21/60 (35.00%)    
Blood and lymphatic system disorders       
Blood and lymphatic system disorders   1/60 (1.67%)  1 1/60 (1.67%)  1 1/60 (1.67%)  1
Gastrointestinal disorders       
Gastrointestinal disorders   4/60 (6.67%)  4 13/60 (21.67%)  15 4/60 (6.67%)  5
Hepatobiliary disorders       
Hepatobiliary disorders   16/60 (26.67%)  16 13/60 (21.67%)  13 12/60 (20.00%)  12
Immune system disorders       
Immune system disorders   0/60 (0.00%)  0 0/60 (0.00%)  0 1/60 (1.67%)  1
Investigations       
Investigations   1/60 (1.67%)  1 1/60 (1.67%)  1 0/60 (0.00%)  0
Metabolism and nutrition disorders       
Metabolism and Nutrition Disorders   0/60 (0.00%)  0 1/60 (1.67%)  1 0/60 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Musculoskeletal and connective tissue disorders   2/60 (3.33%)  2 3/60 (5.00%)  3 3/60 (5.00%)  3
Nervous system disorders       
Nervous system disorder   1/60 (1.67%)  1 1/60 (1.67%)  1 0/60 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Respiratory, thoracic and mediastinal disorders   0/60 (0.00%)  0 3/60 (5.00%)  3 1/60 (1.67%)  1
Skin and subcutaneous tissue disorders       
Skin and subcutaneous tissue disorders   6/60 (10.00%)  6 1/60 (1.67%)  1 7/60 (11.67%)  8
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Carole Mitnick
Organization: Harvard Medical School
Phone: 617-432-6018
EMail: Carole_Mitnick@hms.harvard.edu
Layout table for additonal information
Responsible Party: Carole Mitnick, Harvard University Faculty of Medicine
ClinicalTrials.gov Identifier: NCT01408914    
Other Study ID Numbers: 11-0050
5U01AI091429-03 ( U.S. NIH Grant/Contract )
First Submitted: August 2, 2011
First Posted: August 3, 2011
Results First Submitted: May 3, 2017
Results First Posted: July 13, 2017
Last Update Posted: November 20, 2017