Trial Outcomes & Findings for Improving Retreatment Success (IMPRESS) (NCT NCT02114684)
NCT ID: NCT02114684
Last Updated: 2019-08-05
Results Overview
The proportion of patients with negative sputum cultures at the end of the intensive phase (8 weeks) and the proportion of patients with negative sputum cultures at 6 months were compared between the two study arms. All participants with sputum culture results at week 8 and month 6 were included in the analysis.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
197 participants
Primary outcome timeframe
24 weeks
Results posted on
2019-08-05
Participant Flow
One individual in the control arm was terminated one month after enrollment owing to discovery of pre-existing violation of entry criteria. The individual was excluded from all statistical analyses.
Participant milestones
| Measure |
Moxifloxacin
A Moxifloxacin-containing oral regimen of Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Moxifloxacin (M), substituting Moxifloxacin for Ethambutol.
The intervention arm substituted moxifloxacin for ethambutol (moxifloxacin group), and consisted of daily doses of moxifloxacin, rifampicin, isoniazid and pyrazinamide for 8 weeks, followed by daily doses of moxifloxacin, rifampicin and isoniazid for 16 weeks.
Participants in the moxifloxacin arm received daily 400 mg of moxifloxacin (Avelox®, Bayer Healthcare), weight-based rifampicin at 450 or 600 mg, and 225 or 300 mg of isoniazid, for participants 38-54 and ≥55 kg, respectively, during the 2-month intensive phase and 4-month continuation phase of TB treatment. During the intensive phase of treatment, pyrazinamide was used at 1500 and 2000mg in participants between 38-54 and ≥55 kg, respectively.
|
Control
An Ethambutol oral regimen of Isoniazid (H), Rifampicin(R), Pyrazinamide (Z), Ethambutol(E), substituting Ethambutol for Moxifloxacin.
Daily doses of rifampicin, isoniazid, pyrazinamide and ethambutol for 8 weeks (intensive phase), followed by daily doses of rifampicin and isoniazid for 16 weeks (Continuation phase).
During the first two months (intensive phase) of treatment, participants in the control arm received the following weight-based doses by fixed dose combination tablets: Participants who were 38 - 54kg received rifampicin 450mg, isoniazid 225mg, pyrazinamide 1200mg, ethambutol 825mg; participants who were 54 - 70kg received rifampicin 600mg, isoniazid 300mg, pyrazinamide 1600mg, ethambutol 1100mg; participants who were \> 70 kg received rifampicin 750mg, isoniazid 375mg, pyrazinamide 2000mg, ethambutol 1375mg. During the subsequent four months (continuation phase), participants continued on the same weight-based doses of rifampicin and isoniazid.
|
|---|---|---|
|
Overall Study
STARTED
|
98
|
98
|
|
Overall Study
COMPLETED
|
86
|
88
|
|
Overall Study
NOT COMPLETED
|
12
|
10
|
Reasons for withdrawal
| Measure |
Moxifloxacin
A Moxifloxacin-containing oral regimen of Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Moxifloxacin (M), substituting Moxifloxacin for Ethambutol.
The intervention arm substituted moxifloxacin for ethambutol (moxifloxacin group), and consisted of daily doses of moxifloxacin, rifampicin, isoniazid and pyrazinamide for 8 weeks, followed by daily doses of moxifloxacin, rifampicin and isoniazid for 16 weeks.
Participants in the moxifloxacin arm received daily 400 mg of moxifloxacin (Avelox®, Bayer Healthcare), weight-based rifampicin at 450 or 600 mg, and 225 or 300 mg of isoniazid, for participants 38-54 and ≥55 kg, respectively, during the 2-month intensive phase and 4-month continuation phase of TB treatment. During the intensive phase of treatment, pyrazinamide was used at 1500 and 2000mg in participants between 38-54 and ≥55 kg, respectively.
|
Control
An Ethambutol oral regimen of Isoniazid (H), Rifampicin(R), Pyrazinamide (Z), Ethambutol(E), substituting Ethambutol for Moxifloxacin.
Daily doses of rifampicin, isoniazid, pyrazinamide and ethambutol for 8 weeks (intensive phase), followed by daily doses of rifampicin and isoniazid for 16 weeks (Continuation phase).
During the first two months (intensive phase) of treatment, participants in the control arm received the following weight-based doses by fixed dose combination tablets: Participants who were 38 - 54kg received rifampicin 450mg, isoniazid 225mg, pyrazinamide 1200mg, ethambutol 825mg; participants who were 54 - 70kg received rifampicin 600mg, isoniazid 300mg, pyrazinamide 1600mg, ethambutol 1100mg; participants who were \> 70 kg received rifampicin 750mg, isoniazid 375mg, pyrazinamide 2000mg, ethambutol 1375mg. During the subsequent four months (continuation phase), participants continued on the same weight-based doses of rifampicin and isoniazid.
|
|---|---|---|
|
Overall Study
Death
|
6
|
4
|
|
Overall Study
Lost to Follow-up
|
1
|
2
|
|
Overall Study
Withdrawal by Subject
|
1
|
2
|
|
Overall Study
Relocation
|
3
|
1
|
|
Overall Study
Rifampicin resistant on culture
|
0
|
1
|
|
Overall Study
Patient Incarcerated
|
1
|
0
|
Baseline Characteristics
Improving Retreatment Success (IMPRESS)
Baseline characteristics by cohort
| Measure |
Moxifloxacin
n=98 Participants
A Moxifloxacin-containing oral regimen of Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Moxifloxacin (M), substituting Moxifloxacin for Ethambutol.
The intervention arm substituted moxifloxacin for ethambutol (moxifloxacin group), and consisted of daily doses of moxifloxacin, rifampicin, isoniazid and pyrazinamide for 8 weeks, followed by daily doses of moxifloxacin, rifampicin and isoniazid for 16 weeks.
Participants in the moxifloxacin arm received daily 400 mg of moxifloxacin (Avelox®, Bayer Healthcare), weight-based rifampicin at 450 or 600 mg, and 225 or 300 mg of isoniazid, for participants 38-54 and ≥55 kg, respectively, during the 2-month intensive phase and 4-month continuation phase of TB treatment. During the intensive phase of treatment, pyrazinamide was used at 1500 and 2000mg in participants between 38-54 and ≥55 kg, respectively.
|
Control
n=98 Participants
An Ethambutol oral regimen of Isoniazid (H), Rifampicin(R), Pyrazinamide (Z), Ethambutol(E), substituting Ethambutol for Moxifloxacin.
Daily doses of rifampicin, isoniazid, pyrazinamide and ethambutol for 8 weeks (intensive phase), followed by daily doses of rifampicin and isoniazid for 16 weeks (Continuation phase).
During the first two months (intensive phase) of treatment, participants in the control arm received the following weight-based doses by fixed dose combination tablets: Participants who were 38 - 54kg received rifampicin 450mg, isoniazid 225mg, pyrazinamide 1200mg, ethambutol 825mg; participants who were 54 - 70kg received rifampicin 600mg, isoniazid 300mg, pyrazinamide 1600mg, ethambutol 1100mg; participants who were \> 70 kg received rifampicin 750mg, isoniazid 375mg, pyrazinamide 2000mg, ethambutol 1375mg. During the subsequent four months (continuation phase), participants continued on the same weight-based doses of rifampicin and isoniazid.
|
Total
n=196 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
<25 years
|
7 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Age, Customized
=>25 and <35 years
|
37 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
72 Participants
n=5 Participants
|
|
Age, Customized
=>35 and <=45 years
|
35 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
67 Participants
n=5 Participants
|
|
Age, Customized
>45 years
|
19 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
24 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
59 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
74 Participants
n=5 Participants
|
63 Participants
n=7 Participants
|
137 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 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
|
|
Race (NIH/OMB)
Black or African American
|
96 Participants
n=5 Participants
|
98 Participants
n=7 Participants
|
194 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
South Africa
|
98 Participants
n=5 Participants
|
98 Participants
n=7 Participants
|
196 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 24 weeksPopulation: Nine participants had missing data at week 8: 4 missed visits, 3 terminated before week 8 and 2 had MOTT cultured. Fourteen had missing data at month 6: 7 were terminated before month 6 and 7 missed their visits.
The proportion of patients with negative sputum cultures at the end of the intensive phase (8 weeks) and the proportion of patients with negative sputum cultures at 6 months were compared between the two study arms. All participants with sputum culture results at week 8 and month 6 were included in the analysis.
Outcome measures
| Measure |
Moxifloxacin
n=98 Participants
A Moxifloxacin-containing oral regimen of Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Moxifloxacin (M), substituting Moxifloxacin for Ethambutol.
The intervention arm substituted moxifloxacin for ethambutol (moxifloxacin group), and consisted of daily doses of moxifloxacin, rifampicin, isoniazid and pyrazinamide for 8 weeks, followed by daily doses of moxifloxacin, rifampicin and isoniazid for 16 weeks.
Participants in the moxifloxacin arm received daily 400 mg of moxifloxacin (Avelox®, Bayer Healthcare), weight-based rifampicin at 450 or 600 mg, and 225 or 300 mg of isoniazid, for participants 38-54 and ≥55 kg, respectively, during the 2-month intensive phase and 4-month continuation phase of TB treatment. During the intensive phase of treatment, pyrazinamide was used at 1500 and 2000mg in participants between 38-54 and ≥55 kg, respectively.
|
Control
n=98 Participants
An Ethambutol oral regimen of Isoniazid (H), Rifampicin(R), Pyrazinamide (Z), Ethambutol(E), substituting Ethambutol for Moxifloxacin.
Daily doses of rifampicin, isoniazid, pyrazinamide and ethambutol for 8 weeks (intensive phase), followed by daily doses of rifampicin and isoniazid for 16 weeks (Continuation phase).
During the first two months (intensive phase) of treatment, participants in the control arm received the following weight-based doses by fixed dose combination tablets: Participants who were 38 - 54kg received rifampicin 450mg, isoniazid 225mg, pyrazinamide 1200mg, ethambutol 825mg; participants who were 54 - 70kg received rifampicin 600mg, isoniazid 300mg, pyrazinamide 1600mg, ethambutol 1100mg; participants who were \> 70 kg received rifampicin 750mg, isoniazid 375mg, pyrazinamide 2000mg, ethambutol 1375mg. During the subsequent four months (continuation phase), participants continued on the same weight-based doses of rifampicin and isoniazid.
|
HIV Negative, Moxifloxacin
HIV negative participants based on HIV status at study enrollment, who were assigned to the Moxifloxacin arm
|
HIV Negative, Control
HIV negative participants based on HIV status at study enrollment, who were assigned to the control group
|
|---|---|---|---|---|
|
Sputum Culture Conversion Rates at Week 8 and Month 6 Post Tuberculosis Treatment Initiation
culture negative at 8 weeks
|
78 Participants
|
73 Participants
|
—
|
—
|
|
Sputum Culture Conversion Rates at Week 8 and Month 6 Post Tuberculosis Treatment Initiation
culture negative at 6 months
|
84 Participants
|
92 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 2 yearsTo determine the time to culture-conversion of the moxifloxacin regimen and the ethambutol regimen.
Outcome measures
| Measure |
Moxifloxacin
n=98 Participants
A Moxifloxacin-containing oral regimen of Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Moxifloxacin (M), substituting Moxifloxacin for Ethambutol.
The intervention arm substituted moxifloxacin for ethambutol (moxifloxacin group), and consisted of daily doses of moxifloxacin, rifampicin, isoniazid and pyrazinamide for 8 weeks, followed by daily doses of moxifloxacin, rifampicin and isoniazid for 16 weeks.
Participants in the moxifloxacin arm received daily 400 mg of moxifloxacin (Avelox®, Bayer Healthcare), weight-based rifampicin at 450 or 600 mg, and 225 or 300 mg of isoniazid, for participants 38-54 and ≥55 kg, respectively, during the 2-month intensive phase and 4-month continuation phase of TB treatment. During the intensive phase of treatment, pyrazinamide was used at 1500 and 2000mg in participants between 38-54 and ≥55 kg, respectively.
|
Control
n=98 Participants
An Ethambutol oral regimen of Isoniazid (H), Rifampicin(R), Pyrazinamide (Z), Ethambutol(E), substituting Ethambutol for Moxifloxacin.
Daily doses of rifampicin, isoniazid, pyrazinamide and ethambutol for 8 weeks (intensive phase), followed by daily doses of rifampicin and isoniazid for 16 weeks (Continuation phase).
During the first two months (intensive phase) of treatment, participants in the control arm received the following weight-based doses by fixed dose combination tablets: Participants who were 38 - 54kg received rifampicin 450mg, isoniazid 225mg, pyrazinamide 1200mg, ethambutol 825mg; participants who were 54 - 70kg received rifampicin 600mg, isoniazid 300mg, pyrazinamide 1600mg, ethambutol 1100mg; participants who were \> 70 kg received rifampicin 750mg, isoniazid 375mg, pyrazinamide 2000mg, ethambutol 1375mg. During the subsequent four months (continuation phase), participants continued on the same weight-based doses of rifampicin and isoniazid.
|
HIV Negative, Moxifloxacin
HIV negative participants based on HIV status at study enrollment, who were assigned to the Moxifloxacin arm
|
HIV Negative, Control
HIV negative participants based on HIV status at study enrollment, who were assigned to the control group
|
|---|---|---|---|---|
|
Time to Culture-conversion of the Moxifloxacin Regimen and the Ethambutol Regimen
|
6.0 weeks
Interval 4.0 to 8.3
|
7.9 weeks
Interval 4.0 to 11.4
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 2 yearsTo compare the proportion of patients with any Grade 3 or 4 adverse reactions in the two study arms. Outcome measured in terms of number of participants with at least one grade 3 or 4 events, and not in number of events.
Outcome measures
| Measure |
Moxifloxacin
n=98 Participants
A Moxifloxacin-containing oral regimen of Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Moxifloxacin (M), substituting Moxifloxacin for Ethambutol.
The intervention arm substituted moxifloxacin for ethambutol (moxifloxacin group), and consisted of daily doses of moxifloxacin, rifampicin, isoniazid and pyrazinamide for 8 weeks, followed by daily doses of moxifloxacin, rifampicin and isoniazid for 16 weeks.
Participants in the moxifloxacin arm received daily 400 mg of moxifloxacin (Avelox®, Bayer Healthcare), weight-based rifampicin at 450 or 600 mg, and 225 or 300 mg of isoniazid, for participants 38-54 and ≥55 kg, respectively, during the 2-month intensive phase and 4-month continuation phase of TB treatment. During the intensive phase of treatment, pyrazinamide was used at 1500 and 2000mg in participants between 38-54 and ≥55 kg, respectively.
|
Control
n=98 Participants
An Ethambutol oral regimen of Isoniazid (H), Rifampicin(R), Pyrazinamide (Z), Ethambutol(E), substituting Ethambutol for Moxifloxacin.
Daily doses of rifampicin, isoniazid, pyrazinamide and ethambutol for 8 weeks (intensive phase), followed by daily doses of rifampicin and isoniazid for 16 weeks (Continuation phase).
During the first two months (intensive phase) of treatment, participants in the control arm received the following weight-based doses by fixed dose combination tablets: Participants who were 38 - 54kg received rifampicin 450mg, isoniazid 225mg, pyrazinamide 1200mg, ethambutol 825mg; participants who were 54 - 70kg received rifampicin 600mg, isoniazid 300mg, pyrazinamide 1600mg, ethambutol 1100mg; participants who were \> 70 kg received rifampicin 750mg, isoniazid 375mg, pyrazinamide 2000mg, ethambutol 1375mg. During the subsequent four months (continuation phase), participants continued on the same weight-based doses of rifampicin and isoniazid.
|
HIV Negative, Moxifloxacin
HIV negative participants based on HIV status at study enrollment, who were assigned to the Moxifloxacin arm
|
HIV Negative, Control
HIV negative participants based on HIV status at study enrollment, who were assigned to the control group
|
|---|---|---|---|---|
|
Proportion of Patients With Any Grade 3 or 4 Adverse Reactions in the Two Study Arms
|
43 Participants
|
25 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 2 years for adverse events and 8 weeks for culture conversion ratesPopulation: 9 participants had missing data at 8 weeks: 4 missed visits, 3 terminated before week 8, and 2 had MOTT cultured
To compare adverse events and 8-week culture conversion rates among HIV-infected patients vs. HIV-uninfected patients. The proportion of participants with at least one grade 3 or 4 adverse event was measured.
Outcome measures
| Measure |
Moxifloxacin
n=70 Participants
A Moxifloxacin-containing oral regimen of Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Moxifloxacin (M), substituting Moxifloxacin for Ethambutol.
The intervention arm substituted moxifloxacin for ethambutol (moxifloxacin group), and consisted of daily doses of moxifloxacin, rifampicin, isoniazid and pyrazinamide for 8 weeks, followed by daily doses of moxifloxacin, rifampicin and isoniazid for 16 weeks.
Participants in the moxifloxacin arm received daily 400 mg of moxifloxacin (Avelox®, Bayer Healthcare), weight-based rifampicin at 450 or 600 mg, and 225 or 300 mg of isoniazid, for participants 38-54 and ≥55 kg, respectively, during the 2-month intensive phase and 4-month continuation phase of TB treatment. During the intensive phase of treatment, pyrazinamide was used at 1500 and 2000mg in participants between 38-54 and ≥55 kg, respectively.
|
Control
n=68 Participants
An Ethambutol oral regimen of Isoniazid (H), Rifampicin(R), Pyrazinamide (Z), Ethambutol(E), substituting Ethambutol for Moxifloxacin.
Daily doses of rifampicin, isoniazid, pyrazinamide and ethambutol for 8 weeks (intensive phase), followed by daily doses of rifampicin and isoniazid for 16 weeks (Continuation phase).
During the first two months (intensive phase) of treatment, participants in the control arm received the following weight-based doses by fixed dose combination tablets: Participants who were 38 - 54kg received rifampicin 450mg, isoniazid 225mg, pyrazinamide 1200mg, ethambutol 825mg; participants who were 54 - 70kg received rifampicin 600mg, isoniazid 300mg, pyrazinamide 1600mg, ethambutol 1100mg; participants who were \> 70 kg received rifampicin 750mg, isoniazid 375mg, pyrazinamide 2000mg, ethambutol 1375mg. During the subsequent four months (continuation phase), participants continued on the same weight-based doses of rifampicin and isoniazid.
|
HIV Negative, Moxifloxacin
n=28 Participants
HIV negative participants based on HIV status at study enrollment, who were assigned to the Moxifloxacin arm
|
HIV Negative, Control
n=30 Participants
HIV negative participants based on HIV status at study enrollment, who were assigned to the control group
|
|---|---|---|---|---|
|
Number of Participants With Adverse Events and 8-week Culture Conversion Rates Among HIV-infected Patients vs. HIV-uninfected Patients
participants with grade 3/4 adverse events
|
30 Participants
|
19 Participants
|
13 Participants
|
6 Participants
|
|
Number of Participants With Adverse Events and 8-week Culture Conversion Rates Among HIV-infected Patients vs. HIV-uninfected Patients
participants culture negative at 8 weeks
|
57 Participants
|
51 Participants
|
21 Participants
|
22 Participants
|
SECONDARY outcome
Timeframe: up to 2 yearsA patient was defined as having an unfavourable outcome if he/she was not cured at the end of treatment or did not successfully complete treatment. Recurrence after completion of treatment was defined as two positive cultures within a period of four months without an intervening negative culture.
Outcome measures
| Measure |
Moxifloxacin
n=98 Participants
A Moxifloxacin-containing oral regimen of Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Moxifloxacin (M), substituting Moxifloxacin for Ethambutol.
The intervention arm substituted moxifloxacin for ethambutol (moxifloxacin group), and consisted of daily doses of moxifloxacin, rifampicin, isoniazid and pyrazinamide for 8 weeks, followed by daily doses of moxifloxacin, rifampicin and isoniazid for 16 weeks.
Participants in the moxifloxacin arm received daily 400 mg of moxifloxacin (Avelox®, Bayer Healthcare), weight-based rifampicin at 450 or 600 mg, and 225 or 300 mg of isoniazid, for participants 38-54 and ≥55 kg, respectively, during the 2-month intensive phase and 4-month continuation phase of TB treatment. During the intensive phase of treatment, pyrazinamide was used at 1500 and 2000mg in participants between 38-54 and ≥55 kg, respectively.
|
Control
n=98 Participants
An Ethambutol oral regimen of Isoniazid (H), Rifampicin(R), Pyrazinamide (Z), Ethambutol(E), substituting Ethambutol for Moxifloxacin.
Daily doses of rifampicin, isoniazid, pyrazinamide and ethambutol for 8 weeks (intensive phase), followed by daily doses of rifampicin and isoniazid for 16 weeks (Continuation phase).
During the first two months (intensive phase) of treatment, participants in the control arm received the following weight-based doses by fixed dose combination tablets: Participants who were 38 - 54kg received rifampicin 450mg, isoniazid 225mg, pyrazinamide 1200mg, ethambutol 825mg; participants who were 54 - 70kg received rifampicin 600mg, isoniazid 300mg, pyrazinamide 1600mg, ethambutol 1100mg; participants who were \> 70 kg received rifampicin 750mg, isoniazid 375mg, pyrazinamide 2000mg, ethambutol 1375mg. During the subsequent four months (continuation phase), participants continued on the same weight-based doses of rifampicin and isoniazid.
|
HIV Negative, Moxifloxacin
HIV negative participants based on HIV status at study enrollment, who were assigned to the Moxifloxacin arm
|
HIV Negative, Control
HIV negative participants based on HIV status at study enrollment, who were assigned to the control group
|
|---|---|---|---|---|
|
Proportion of Patients With Unfavourable Outcomes or Tuberculosis Recurrence in the Moxifloxacin and Control Arm.
|
13 Participants
|
6 Participants
|
—
|
—
|
Adverse Events
Moxifloxacin
Serious events: 27 serious events
Other events: 30 other events
Deaths: 6 deaths
Control
Serious events: 12 serious events
Other events: 19 other events
Deaths: 4 deaths
Serious adverse events
| Measure |
Moxifloxacin
n=98 participants at risk
A Moxifloxacin-containing oral regimen of Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Moxifloxacin (M), substituting Moxifloxacin for Ethambutol.
The intervention arm substituted moxifloxacin for ethambutol (moxifloxacin group), and consisted of daily doses of moxifloxacin, rifampicin, isoniazid and pyrazinamide for 8 weeks, followed by daily doses of moxifloxacin, rifampicin and isoniazid for 16 weeks.
Participants in the moxifloxacin arm received daily 400 mg of moxifloxacin (Avelox®, Bayer Healthcare), weight-based rifampicin at 450 or 600 mg, and 225 or 300 mg of isoniazid, for participants 38-54 and ≥55 kg, respectively, during the 2-month intensive phase and 4-month continuation phase of TB treatment. During the intensive phase of treatment, pyrazinamide was used at 1500 and 2000mg in participants between 38-54 and ≥55 kg, respectively.
|
Control
n=98 participants at risk
An Ethambutol oral regimen of Isoniazid (H), Rifampicin(R), Pyrazinamide (Z), Ethambutol(E), substituting Ethambutol for Moxifloxacin.
Daily doses of rifampicin, isoniazid, pyrazinamide and ethambutol for 8 weeks (intensive phase), followed by daily doses of rifampicin and isoniazid for 16 weeks (Continuation phase).
During the first two months (intensive phase) of treatment, participants in the control arm received the following weight-based doses by fixed dose combination tablets: Participants who were 38 - 54kg received rifampicin 450mg, isoniazid 225mg, pyrazinamide 1200mg, ethambutol 825mg; participants who were 54 - 70kg received rifampicin 600mg, isoniazid 300mg, pyrazinamide 1600mg, ethambutol 1100mg; participants who were \> 70 kg received rifampicin 750mg, isoniazid 375mg, pyrazinamide 2000mg, ethambutol 1375mg. During the subsequent four months (continuation phase), participants continued on the same weight-based doses of rifampicin and isoniazid.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.0%
1/98 • Number of events 1 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/98 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Blood and lymphatic system disorders
Neutropenia
|
1.0%
1/98 • Number of events 2 • 2 years
|
0.00%
0/98 • 2 years
|
|
Eye disorders
Visual acuity reduced
|
0.00%
0/98 • 2 years
|
4.1%
4/98 • Number of events 4 • 2 years
|
|
Gastrointestinal disorders
Pancreatitis acute
|
2.0%
2/98 • Number of events 2 • 2 years
|
0.00%
0/98 • 2 years
|
|
Gastrointestinal disorders
Haemorrhoids
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
General disorders
Injection site paraesthesia
|
0.00%
0/98 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
General disorders
Death
|
3.1%
3/98 • Number of events 3 • 2 years
|
3.1%
3/98 • Number of events 3 • 2 years
|
|
General disorders
Non-cardiac chest pain
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
General disorders
Treatment failure
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Hepatobiliary disorders
Hepatitis
|
2.0%
2/98 • Number of events 2 • 2 years
|
0.00%
0/98 • 2 years
|
|
Infections and infestations
Nosocomial infection
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Infections and infestations
Cellulitis
|
1.0%
1/98 • Number of events 1 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Infections and infestations
Gastroenteritis
|
1.0%
1/98 • Number of events 1 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Infections and infestations
Abscess
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Infections and infestations
Bronchopneumonia
|
0.00%
0/98 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/98 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Infections and infestations
Lung abscess
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Infections and infestations
Pneumonia
|
1.0%
1/98 • Number of events 1 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Infections and infestations
Scrotal abscess
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Infections and infestations
Sepsis
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Infections and infestations
Wound sepsis
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Infections and infestations
Disseminated tuberculosis
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Infections and infestations
Pulmonary tuberculosis
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Infections and infestations
Tuberculosis
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Infections and infestations
Hepatitis B
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Infections and infestations
Herpes zoster
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Infections and infestations
Epidemic vomiting syndrome
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Injury, poisoning and procedural complications
Head injury
|
2.0%
2/98 • Number of events 2 • 2 years
|
0.00%
0/98 • 2 years
|
|
Investigations
Platelet count decreased
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Investigations
Alanine aminotransferase increased
|
1.0%
1/98 • Number of events 1 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Investigations
Aspartate aminotransferase increased
|
2.0%
2/98 • Number of events 2 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Investigations
Neurological examination abnormal
|
0.00%
0/98 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Investigations
Weight decreased
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Investigations
Creatinine renal clearance decreased
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Investigations
Blood osmolarity decreased
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Metabolism and nutrition disorders
Decreased appetite
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Nervous system disorders
Optic neuritis
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Nervous system disorders
Trigeminal neuralgia
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Psychiatric disorders
Confusional state
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Psychiatric disorders
Acute psychosis
|
1.0%
1/98 • Number of events 1 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Psychiatric disorders
Psychotic disorder
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/98 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Bronchiectasis
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Emphysema
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
2.0%
2/98 • Number of events 2 • 2 years
|
0.00%
0/98 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
4.1%
4/98 • Number of events 4 • 2 years
|
0.00%
0/98 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
1.0%
1/98 • Number of events 2 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Surgical and medical procedures
Bach's flower remedy
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/98 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
Other adverse events
| Measure |
Moxifloxacin
n=98 participants at risk
A Moxifloxacin-containing oral regimen of Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Moxifloxacin (M), substituting Moxifloxacin for Ethambutol.
The intervention arm substituted moxifloxacin for ethambutol (moxifloxacin group), and consisted of daily doses of moxifloxacin, rifampicin, isoniazid and pyrazinamide for 8 weeks, followed by daily doses of moxifloxacin, rifampicin and isoniazid for 16 weeks.
Participants in the moxifloxacin arm received daily 400 mg of moxifloxacin (Avelox®, Bayer Healthcare), weight-based rifampicin at 450 or 600 mg, and 225 or 300 mg of isoniazid, for participants 38-54 and ≥55 kg, respectively, during the 2-month intensive phase and 4-month continuation phase of TB treatment. During the intensive phase of treatment, pyrazinamide was used at 1500 and 2000mg in participants between 38-54 and ≥55 kg, respectively.
|
Control
n=98 participants at risk
An Ethambutol oral regimen of Isoniazid (H), Rifampicin(R), Pyrazinamide (Z), Ethambutol(E), substituting Ethambutol for Moxifloxacin.
Daily doses of rifampicin, isoniazid, pyrazinamide and ethambutol for 8 weeks (intensive phase), followed by daily doses of rifampicin and isoniazid for 16 weeks (Continuation phase).
During the first two months (intensive phase) of treatment, participants in the control arm received the following weight-based doses by fixed dose combination tablets: Participants who were 38 - 54kg received rifampicin 450mg, isoniazid 225mg, pyrazinamide 1200mg, ethambutol 825mg; participants who were 54 - 70kg received rifampicin 600mg, isoniazid 300mg, pyrazinamide 1600mg, ethambutol 1100mg; participants who were \> 70 kg received rifampicin 750mg, isoniazid 375mg, pyrazinamide 2000mg, ethambutol 1375mg. During the subsequent four months (continuation phase), participants continued on the same weight-based doses of rifampicin and isoniazid.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
2.0%
2/98 • Number of events 2 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Blood and lymphatic system disorders
Normochromic normocytic anaemia
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Blood and lymphatic system disorders
Neutropenia
|
6.1%
6/98 • Number of events 7 • 2 years
|
2.0%
2/98 • Number of events 2 • 2 years
|
|
Endocrine disorders
Inappropriate antidiuretic hormone secretion
|
0.00%
0/98 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Eye disorders
Visual acuity reduced
|
0.00%
0/98 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Gastrointestinal disorders
Diarrhoea
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Gastrointestinal disorders
Nausea
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
General disorders
Fatigue
|
1.0%
1/98 • Number of events 1 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
General disorders
Chest pain
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/98 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Hepatobiliary disorders
Acute hepatic failure
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Infections and infestations
Pneumonia
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Infections and infestations
Sputum purulent
|
0.00%
0/98 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Infections and infestations
Bone tuberculosis
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Infections and infestations
Disseminated tuberculosis
|
0.00%
0/98 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Infections and infestations
Extrapulmonary tuberculosis
|
2.0%
2/98 • Number of events 2 • 2 years
|
0.00%
0/98 • 2 years
|
|
Infections and infestations
Tuberculosis
|
0.00%
0/98 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Infections and infestations
Hepatitis B
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Investigations
Amylase increased
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Investigations
Alanine aminotransferase increased
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Investigations
Aspartate aminotransferase increased
|
4.1%
4/98 • Number of events 4 • 2 years
|
0.00%
0/98 • 2 years
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/98 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Investigations
Weight decreased
|
5.1%
5/98 • Number of events 5 • 2 years
|
2.0%
2/98 • Number of events 2 • 2 years
|
|
Investigations
Blood creatinine increased
|
0.00%
0/98 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Investigations
Creatinine renal clearance decreased
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Metabolism and nutrition disorders
Decreased appetite
|
2.0%
2/98 • Number of events 3 • 2 years
|
2.0%
2/98 • Number of events 2 • 2 years
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
1.0%
1/98 • Number of events 1 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/98 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Metabolism and nutrition disorders
Hyperamylasaemia
|
0.00%
0/98 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
4.1%
4/98 • Number of events 4 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Metabolism and nutrition disorders
Gout
|
1.0%
1/98 • Number of events 1 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
2.0%
2/98 • Number of events 2 • 2 years
|
2.0%
2/98 • Number of events 2 • 2 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Female reproductive tract carcinoma in situ
|
0.00%
0/98 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Nervous system disorders
Ataxia
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Psychiatric disorders
Suicidal ideation
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Renal and urinary disorders
Haematuria
|
1.0%
1/98 • Number of events 1 • 2 years
|
2.0%
2/98 • Number of events 3 • 2 years
|
|
Reproductive system and breast disorders
Gynaecomastia
|
0.00%
0/98 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/98 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Skin and subcutaneous tissue disorders
Dermatitis allergic
|
0.00%
0/98 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Skin and subcutaneous tissue disorders
Rash generalised
|
0.00%
0/98 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
|
Vascular disorders
Hypotension
|
1.0%
1/98 • Number of events 1 • 2 years
|
0.00%
0/98 • 2 years
|
|
Vascular disorders
Hypertension
|
0.00%
0/98 • 2 years
|
1.0%
1/98 • Number of events 1 • 2 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place