Trial Outcomes & Findings for Retapamulin Versus Placebo in Secondarily-Infected Traumatic Lesions (SITL) (NCT NCT00684177)
NCT ID: NCT00684177
Last Updated: 2016-11-23
Results Overview
"Clinical Success" at follow-up was defined as "Resolution of clinically meaningful signs and symptoms of infection recorded at baseline including a pus/exudate Skin Infection Rating Scale (SIRS) score of "0". Clinical response at follow-up was classified as "Clinical Failure" for all other cases. The SIRS consists of seven items (pus/exudates, crusting, erythema/inflammation, tissue warmth, tissue edema, itching and pain). Each item has a score ranging from 0 to 6 (0=absent, 6=severe). The SIRS total score was calculated as the sum of the scores of all 7 SIRS items.
COMPLETED
PHASE3
508 participants
Days 12-14
2016-11-23
Participant Flow
A total of 508 participants were randomized. One participant did not receive treatment; thus, no data were collected for this participant. Only 507 participants were included in the analysis.
Participant milestones
| Measure |
Retapamulin
Topical retapamulin ointment, 1% twice daily for 5 days
|
Placebo
Matching placebo
|
|---|---|---|
|
Overall Study
STARTED
|
343
|
164
|
|
Overall Study
COMPLETED
|
322
|
141
|
|
Overall Study
NOT COMPLETED
|
21
|
23
|
Reasons for withdrawal
| Measure |
Retapamulin
Topical retapamulin ointment, 1% twice daily for 5 days
|
Placebo
Matching placebo
|
|---|---|---|
|
Overall Study
Adverse Event
|
4
|
3
|
|
Overall Study
Lack of Efficacy
|
10
|
15
|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
2
|
1
|
|
Overall Study
Physician Decision
|
2
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
2
|
|
Overall Study
Other
|
1
|
2
|
Baseline Characteristics
Retapamulin Versus Placebo in Secondarily-Infected Traumatic Lesions (SITL)
Baseline characteristics by cohort
| Measure |
Retapamulin
n=343 Participants
Topical retapamulin ointment, 1% twice daily for 5 days
|
Placebo
n=164 Participants
Matching placebo
|
Total
n=507 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
32.6 years
STANDARD_DEVIATION 18.77 • n=93 Participants
|
28.6 years
STANDARD_DEVIATION 18.32 • n=4 Participants
|
31.3 years
STANDARD_DEVIATION 18.70 • n=27 Participants
|
|
Sex: Female, Male
Female
|
144 Participants
n=93 Participants
|
63 Participants
n=4 Participants
|
207 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
199 Participants
n=93 Participants
|
101 Participants
n=4 Participants
|
300 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
African American/African Heritage
|
144 participants
n=93 Participants
|
71 participants
n=4 Participants
|
215 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaskan Native
|
9 participants
n=93 Participants
|
3 participants
n=4 Participants
|
12 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Asian - Central / South Asian Heritage
|
0 participants
n=93 Participants
|
1 participants
n=4 Participants
|
1 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Asian - East Asian Heritage
|
4 participants
n=93 Participants
|
2 participants
n=4 Participants
|
6 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Asian - South East Asian Heritage
|
33 participants
n=93 Participants
|
15 participants
n=4 Participants
|
48 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
1 participants
n=93 Participants
|
2 participants
n=4 Participants
|
3 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
White - Arabic/North African Heritage
|
1 participants
n=93 Participants
|
0 participants
n=4 Participants
|
1 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
White - White/Caucasian/European Heritage
|
132 participants
n=93 Participants
|
61 participants
n=4 Participants
|
193 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Mixed Race
|
19 participants
n=93 Participants
|
9 participants
n=4 Participants
|
28 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Days 12-14Population: Primary Efficacy Population: ITTC participants (par.) with baseline pus/exudate \>=3 who were enrolled under the original protocol with data captured under eCRF V1 and who were enrolled under protocol amendments with data captured under eCRF V2; ITTC (Intent-to-treat Clinical): all randomized par. who received at least one dose of study medication.
"Clinical Success" at follow-up was defined as "Resolution of clinically meaningful signs and symptoms of infection recorded at baseline including a pus/exudate Skin Infection Rating Scale (SIRS) score of "0". Clinical response at follow-up was classified as "Clinical Failure" for all other cases. The SIRS consists of seven items (pus/exudates, crusting, erythema/inflammation, tissue warmth, tissue edema, itching and pain). Each item has a score ranging from 0 to 6 (0=absent, 6=severe). The SIRS total score was calculated as the sum of the scores of all 7 SIRS items.
Outcome measures
| Measure |
Retapamulin
n=246 Participants
Topical retapamulin ointment, 1% twice daily for 5 days
|
Placebo
n=113 Participants
Matching placebo
|
|---|---|---|
|
Number of Participants With Clinical Success and Failure at Follow-up (7-9 Days Post Therapy) for the Primary Efficacy Population
Clinical Success
|
184 participants
|
75 participants
|
|
Number of Participants With Clinical Success and Failure at Follow-up (7-9 Days Post Therapy) for the Primary Efficacy Population
Clinical Failure
|
62 participants
|
38 participants
|
SECONDARY outcome
Timeframe: Days 12-14Population: ITTB subset of Primary Efficacy Population: participants in the Primary Efficacy Population (see analysis population description in the Primary Outcome section) who had at least one pathogen isolated at the baseline visit.
"Clinical Success" at follow-up was defined as "Resolution of clinically meaningful signs and symptoms of infection recorded at baseline including a pus/exudate Skin Infection Rating Scale (SIRS) score of "0". Clinical response at follow-up was classified as "Clinical Failure" for all other cases. The SIRS consists of seven items (pus/exudates, crusting, erythema/inflammation, tissue warmth, tissue edema, itching and pain). Each item has a score ranging from 0 to 6 (0=absent, 6=severe). The SIRS total score was calculated as the sum of the scores of all 7 SIRS items.
Outcome measures
| Measure |
Retapamulin
n=182 Participants
Topical retapamulin ointment, 1% twice daily for 5 days
|
Placebo
n=84 Participants
Matching placebo
|
|---|---|---|
|
Number of Participants With Clinical Success and Failure at Follow-up (7-9 Days Post Therapy) for the Intent-to-Treat Bacteriology (ITTB) Subset of the Primary Efficacy Population
Clinical Failure
|
43 participants
|
30 participants
|
|
Number of Participants With Clinical Success and Failure at Follow-up (7-9 Days Post Therapy) for the Intent-to-Treat Bacteriology (ITTB) Subset of the Primary Efficacy Population
Clinical Success
|
139 participants
|
54 participants
|
SECONDARY outcome
Timeframe: Days 12-14Population: ITTB subset of Primary Efficacy Population
The "by pathogen" microbiological outcome was determined by comparing the baseline culture results to those at follow-up. The "by subject" microbiological response was "Microbiological Success" if the microbiological outcomes for all baseline pathogens (bps) belong to "Eradication" (elimination of bps), "Presumed Eradication" (clinical outcome was success; no culture was obtained due to lack of culturable material), or "Colonization" (previously unidentified pathogen is identified at end of therapy in participant who is resolved/improved); otherwise, response was "Microbiological Failure".
Outcome measures
| Measure |
Retapamulin
n=182 Participants
Topical retapamulin ointment, 1% twice daily for 5 days
|
Placebo
n=84 Participants
Matching placebo
|
|---|---|---|
|
Number of Participants With Microbiological Success and Failure at Follow-up (7-9 Days Post Therapy)
Microbiological Success
|
139 participants
|
54 participants
|
|
Number of Participants With Microbiological Success and Failure at Follow-up (7-9 Days Post Therapy)
Microbiological Failure
|
43 participants
|
30 participants
|
SECONDARY outcome
Timeframe: Days 7-9Population: Primary Efficacy Population
Clinical outcome is determined by the investigator based on signs and symptoms (S/S) at the end of therapy evaluation. The 4 clincal outcome categories are: clinical success, resolution of clinically meaningful S/S of infection recorded at baseline (BL), including a pus/exudates score of 0; clinical improvement, improvement of S/S of infection recorded at BL to such an extent that no further antimicrobial therapy is necessary; clinical failure, insufficient improvement of deterioration of S/S of infection recorded at BL such that additional antibiotic therapy is required; unable to determine.
Outcome measures
| Measure |
Retapamulin
n=246 Participants
Topical retapamulin ointment, 1% twice daily for 5 days
|
Placebo
n=113 Participants
Matching placebo
|
|---|---|---|
|
Number of Participants With the Indicated Clinical Outcome at End of Therapy (2-4 Days Post Therapy)
Clinical Failure
|
11 participants
|
14 participants
|
|
Number of Participants With the Indicated Clinical Outcome at End of Therapy (2-4 Days Post Therapy)
Unable to Determine
|
3 participants
|
2 participants
|
|
Number of Participants With the Indicated Clinical Outcome at End of Therapy (2-4 Days Post Therapy)
Clinical Improvement
|
102 participants
|
45 participants
|
|
Number of Participants With the Indicated Clinical Outcome at End of Therapy (2-4 Days Post Therapy)
Clinical Success
|
130 participants
|
52 participants
|
SECONDARY outcome
Timeframe: Days 7-9Population: ITTB subset of Primary Efficacy Population
The "by pathogen" microbiological outcome was determined by comparing the baseline culture results to those at follow-up. The results presented below pooled all baseline pathogens (bps). Eradication: elimination of bps. Presumed Eradication: clinical outcome was success; no culture was obtained due to lack of culturable material. Presumed Improvement: clinical outcome was improvement such that no culture was obtained due to lack of culturable material. Persistence: bps still present. Presumed persistence: clinical failure and no culture was obtained.
Outcome measures
| Measure |
Retapamulin
n=243 Participants
Topical retapamulin ointment, 1% twice daily for 5 days
|
Placebo
n=110 Participants
Matching placebo
|
|---|---|---|
|
Number of Baseline Pathogens With the Indicated Microbiological Outcome at End of Therapy (2-4 Days Post Therapy)
Eradication
|
4 baseline pathogens
|
5 baseline pathogens
|
|
Number of Baseline Pathogens With the Indicated Microbiological Outcome at End of Therapy (2-4 Days Post Therapy)
Presumed Eradication
|
137 baseline pathogens
|
49 baseline pathogens
|
|
Number of Baseline Pathogens With the Indicated Microbiological Outcome at End of Therapy (2-4 Days Post Therapy)
Presumed Improvement
|
94 baseline pathogens
|
35 baseline pathogens
|
|
Number of Baseline Pathogens With the Indicated Microbiological Outcome at End of Therapy (2-4 Days Post Therapy)
Persistence
|
3 baseline pathogens
|
13 baseline pathogens
|
|
Number of Baseline Pathogens With the Indicated Microbiological Outcome at End of Therapy (2-4 Days Post Therapy)
Presumed Persistence
|
5 baseline pathogens
|
8 baseline pathogens
|
SECONDARY outcome
Timeframe: Follow-up (Days 12-14)Population: ITTB subset of Primary Efficacy Population
"Therapeutic Success (Succ)" was referred to as both "Clinical Succ" and "Microbiological (Micro) Succ" at Follow-up. "Clinical Succ" was the "Resolution of baseline signs/symptoms of infection with a pus score of "0." A participant was "Micro Succ" if the micro outcome for all baseline pathogens (bps) belonged to "Eradication" (elimination of bps), "Presumed Eradication" (clinical outcome is success; no culturable material), or "Colonization" (new pathogen is identified at end of therapy in participants who are resolved/improved). All other combinations were deemed "Therapeutic Failures."
Outcome measures
| Measure |
Retapamulin
n=182 Participants
Topical retapamulin ointment, 1% twice daily for 5 days
|
Placebo
n=84 Participants
Matching placebo
|
|---|---|---|
|
Number of Participants With Therapeutic Success and Failure at Follow-up (7-9 Days Post Therapy)
Success
|
139 participants
|
54 participants
|
|
Number of Participants With Therapeutic Success and Failure at Follow-up (7-9 Days Post Therapy)
Failure
|
43 participants
|
30 participants
|
Adverse Events
Retapamulin
Placebo
Serious adverse events
| Measure |
Retapamulin
n=342 participants at risk
Topical retapamulin ointment, 1% twice daily for 5 days
|
Placebo
n=165 participants at risk
Matching placebo
|
|---|---|---|
|
Cardiac disorders
Myocardial infarction
|
0.29%
1/342 • Adverse events (AEs) were recorded from the first dose of study medication until study completion. Serious AEs (SAEs) were collected from the time of consent and continued until study completion (including the Follow-up Period).
AEs were collected for all randomized participants (par.) who received at least one dose of study medications (i.e., ITTC Population). Safety data were analyzed based on the actual treatment received. One par. who was randomized to retapamulin treatment but actually received placebo was included in the placebo arm for the safety analyses.
|
0.00%
0/165 • Adverse events (AEs) were recorded from the first dose of study medication until study completion. Serious AEs (SAEs) were collected from the time of consent and continued until study completion (including the Follow-up Period).
AEs were collected for all randomized participants (par.) who received at least one dose of study medications (i.e., ITTC Population). Safety data were analyzed based on the actual treatment received. One par. who was randomized to retapamulin treatment but actually received placebo was included in the placebo arm for the safety analyses.
|
|
Infections and infestations
Pneumococcal pneumonia
|
0.00%
0/342 • Adverse events (AEs) were recorded from the first dose of study medication until study completion. Serious AEs (SAEs) were collected from the time of consent and continued until study completion (including the Follow-up Period).
AEs were collected for all randomized participants (par.) who received at least one dose of study medications (i.e., ITTC Population). Safety data were analyzed based on the actual treatment received. One par. who was randomized to retapamulin treatment but actually received placebo was included in the placebo arm for the safety analyses.
|
0.61%
1/165 • Adverse events (AEs) were recorded from the first dose of study medication until study completion. Serious AEs (SAEs) were collected from the time of consent and continued until study completion (including the Follow-up Period).
AEs were collected for all randomized participants (par.) who received at least one dose of study medications (i.e., ITTC Population). Safety data were analyzed based on the actual treatment received. One par. who was randomized to retapamulin treatment but actually received placebo was included in the placebo arm for the safety analyses.
|
Other adverse events
| Measure |
Retapamulin
n=342 participants at risk
Topical retapamulin ointment, 1% twice daily for 5 days
|
Placebo
n=165 participants at risk
Matching placebo
|
|---|---|---|
|
General disorders
Application site pain
|
1.5%
5/342 • Adverse events (AEs) were recorded from the first dose of study medication until study completion. Serious AEs (SAEs) were collected from the time of consent and continued until study completion (including the Follow-up Period).
AEs were collected for all randomized participants (par.) who received at least one dose of study medications (i.e., ITTC Population). Safety data were analyzed based on the actual treatment received. One par. who was randomized to retapamulin treatment but actually received placebo was included in the placebo arm for the safety analyses.
|
0.00%
0/165 • Adverse events (AEs) were recorded from the first dose of study medication until study completion. Serious AEs (SAEs) were collected from the time of consent and continued until study completion (including the Follow-up Period).
AEs were collected for all randomized participants (par.) who received at least one dose of study medications (i.e., ITTC Population). Safety data were analyzed based on the actual treatment received. One par. who was randomized to retapamulin treatment but actually received placebo was included in the placebo arm for the safety analyses.
|
|
General disorders
Condition aggravated
|
0.88%
3/342 • Adverse events (AEs) were recorded from the first dose of study medication until study completion. Serious AEs (SAEs) were collected from the time of consent and continued until study completion (including the Follow-up Period).
AEs were collected for all randomized participants (par.) who received at least one dose of study medications (i.e., ITTC Population). Safety data were analyzed based on the actual treatment received. One par. who was randomized to retapamulin treatment but actually received placebo was included in the placebo arm for the safety analyses.
|
0.61%
1/165 • Adverse events (AEs) were recorded from the first dose of study medication until study completion. Serious AEs (SAEs) were collected from the time of consent and continued until study completion (including the Follow-up Period).
AEs were collected for all randomized participants (par.) who received at least one dose of study medications (i.e., ITTC Population). Safety data were analyzed based on the actual treatment received. One par. who was randomized to retapamulin treatment but actually received placebo was included in the placebo arm for the safety analyses.
|
|
General disorders
Pyrexia
|
0.00%
0/342 • Adverse events (AEs) were recorded from the first dose of study medication until study completion. Serious AEs (SAEs) were collected from the time of consent and continued until study completion (including the Follow-up Period).
AEs were collected for all randomized participants (par.) who received at least one dose of study medications (i.e., ITTC Population). Safety data were analyzed based on the actual treatment received. One par. who was randomized to retapamulin treatment but actually received placebo was included in the placebo arm for the safety analyses.
|
1.8%
3/165 • Adverse events (AEs) were recorded from the first dose of study medication until study completion. Serious AEs (SAEs) were collected from the time of consent and continued until study completion (including the Follow-up Period).
AEs were collected for all randomized participants (par.) who received at least one dose of study medications (i.e., ITTC Population). Safety data were analyzed based on the actual treatment received. One par. who was randomized to retapamulin treatment but actually received placebo was included in the placebo arm for the safety analyses.
|
Additional Information
GSK Response Center
GlaxoSmithKline
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER