Trial Outcomes & Findings for Evaluation of TNF-α Blockade Effect in Patients With Severe Cutaneous Adverse Drug Reactions (NCT NCT01276314)
NCT ID: NCT01276314
Last Updated: 2017-12-19
Results Overview
Healing was defined as complete re-epithelialization (i.e., the complete absence of erosions). We recorded the time taken by the skin to heal.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
135 participants
Primary outcome timeframe
One to two months for SJS/TEN cases, and one to six months for DRESS cases.
Results posted on
2017-12-19
Participant Flow
SCAR patients were enrolled in the clinical trial from 2009 to 2015 at Chang Gung Memorial Hospital in Taiwan.
We totally recruited 140 participants, but only 135 SCAR participants (including 91 SJS/TEN patients and 44 DRESS patients) were enrolled to analyze. 5 participants in the control group were not included to analyze (3 cases failed a screening with CD4\<200 cells/mm3 and 2 cases as diagnosis change).
Participant milestones
| Measure |
Anti- TNF-a Treatment (SJS/TEN)
1. Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF
2. Fill out the case report form
3. Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis
4. Etanercept administration:
The experimental group received the first dose of Etanercept (25 mg) i.v., followed by two doses per week and maintain 2 to 3 weeks
anti-TNF a: 25mg BIW, SC
|
Control Group (SJS/TEN)
1. Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF
2. Fill out the case report form
3. Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis
4. Drug administration:
The control group of drug delivery: systemic intravenous steroid therapy, the dose is equivalent to prednisolone 1-1.5 mg / kg / day, according to the treatment of 3-4 days gradually decreased dose.
|
Anti- TNF-a Treatment (DRESS)
1. Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF
2. Fill out the case report form
3. Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis
4. Etanercept administration:
The experimental group received the first dose of Etanercept (25 mg) i.v., followed by two doses per week and maintain 2 to 3 weeks
anti-TNF a: 25mg BIW, SC
|
Control Group (DRESS)
1. Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF
2. Fill out the case report form
3. Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis
4. Drug administration:
The control group of drug delivery: systemic intravenous steroid therapy, the dose is equivalent to prednisolone 1-1.5 mg / kg / day, according to the treatment of 3-4 days gradually decreased dose.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
48
|
43
|
22
|
22
|
|
Overall Study
COMPLETED
|
38
|
33
|
18
|
17
|
|
Overall Study
NOT COMPLETED
|
10
|
10
|
4
|
5
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Evaluation of TNF-α Blockade Effect in Patients With Severe Cutaneous Adverse Drug Reactions
Baseline characteristics by cohort
| Measure |
Anti- TNF-a Treatment (SJS/TEN)
n=48 Participants
1. Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF
2. Fill out the case report form
3. Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis
4. Etanercept administration:
The experimental group received the first dose of Etanercept (25 mg) i.v., followed by two doses per week and maintain 2 to 3 weeks
anti-TNF a: 25mg BIW, SC
|
Control Group (SJS/TEN)
n=43 Participants
1. Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF
2. Fill out the case report form
3. Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis
4. Drug administration:
The control group of drug delivery: systemic intravenous steroid therapy, the dose is equivalent to prednisolone 1-1.5 mg / kg / day, according to the treatment of 3-4 days gradually decreased dose.
|
Anti- TNF-a Treatment (DRESS)
n=22 Participants
1. Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF
2. Fill out the case report form
3. Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis
4. Etanercept administration:
The experimental group received the first dose of Etanercept (25 mg) i.v., followed by two doses per week and maintain 2 to 3 weeks
anti-TNF a: 25mg BIW, SC
|
Control Group (DRESS)
n=22 Participants
1. Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF
2. Fill out the case report form
3. Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis
4. Drug administration:
The control group of drug delivery: systemic intravenous steroid therapy, the dose is equivalent to prednisolone 1-1.5 mg / kg / day, according to the treatment of 3-4 days gradually decreased dose.
|
Total
n=135 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
1 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
35 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
78 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
12 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
51 Participants
n=21 Participants
|
|
Age, Continuous
|
52.73 years
STANDARD_DEVIATION 16.78 • n=5 Participants
|
59.84 years
STANDARD_DEVIATION 24.20 • n=7 Participants
|
53.95 years
STANDARD_DEVIATION 17.41 • n=5 Participants
|
60.95 years
STANDARD_DEVIATION 20.39 • n=4 Participants
|
56.53 years
STANDARD_DEVIATION 20.20 • n=21 Participants
|
|
Sex: Female, Male
Female
|
28 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
80 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
55 Participants
n=21 Participants
|
|
Region of Enrollment
Taiwan
|
48 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
22 Participants
n=4 Participants
|
135 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: One to two months for SJS/TEN cases, and one to six months for DRESS cases.Population: We determined if the enrolled participants had SJS/TEN and DRESS using the criteria and histopathological examinations.
Healing was defined as complete re-epithelialization (i.e., the complete absence of erosions). We recorded the time taken by the skin to heal.
Outcome measures
| Measure |
Anti- TNF-a Treatment (SJS/TEN)
n=38 Participants
1. Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF
2. Fill out the case report form
3. Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis
4. Etanercept administration:
The experimental group received the first dose of Etanercept (25 mg) i.v., followed by two doses per week and maintain 2 to 3 weeks
anti-TNF a: 25mg BIW, SC
|
Control Group (SJS/TEN)
n=33 Participants
1. Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF
2. Fill out the case report form
3. Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis
4. Drug administration:
The control group of drug delivery: systemic intravenous steroid therapy, the dose is equivalent to prednisolone 1-1.5 mg / kg / day, according to the treatment of 3-4 days gradually decreased dose.
|
Anti- TNF-a Treatment (DRESS)
n=18 Participants
1. Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF
2. Fill out the case report form
3. Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis
4. Etanercept administration:
The experimental group received the first dose of Etanercept (25 mg) i.v., followed by two doses per week and maintain 2 to 3 weeks
anti-TNF a: 25mg BIW, SC
|
Control Group (DRESS)
n=17 Participants
1. Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF
2. Fill out the case report form
3. Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis
4. Drug administration:
The control group of drug delivery: systemic intravenous steroid therapy, the dose is equivalent to prednisolone 1-1.5 mg / kg / day, according to the treatment of 3-4 days gradually decreased dose.
|
|---|---|---|---|---|
|
Skin Healing Time
|
13.75 days
Interval 4.0 to 41.0
|
19 days
Interval 7.0 to 42.0
|
40.5 days
Interval 18.0 to 117.0
|
34 days
Interval 9.0 to 165.0
|
Adverse Events
Anti- TNF-a Treatment (SJS/TEN)
Serious events: 5 serious events
Other events: 15 other events
Deaths: 0 deaths
Control Group (SJS/TEN)
Serious events: 9 serious events
Other events: 19 other events
Deaths: 0 deaths
Anti- TNF-a Treatment (DRESS)
Serious events: 2 serious events
Other events: 8 other events
Deaths: 0 deaths
Control Group (DRESS)
Serious events: 5 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Anti- TNF-a Treatment (SJS/TEN)
n=48 participants at risk
1. Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF
2. Fill out the case report form
3. Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis
4. Etanercept administration:
The experimental group received the first dose of Etanercept (25 mg) i.v., followed by two doses per week and maintain 2 to 3 weeks
anti-TNF a: 25mg BIW, SC
|
Control Group (SJS/TEN)
n=43 participants at risk
1. Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF
2. Fill out the case report form
3. Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis
4. Drug administration:
The control group of drug delivery: systemic intravenous steroid therapy, the dose is equivalent to prednisolone 1-1.5 mg / kg / day, according to the treatment of 3-4 days gradually decreased dose.
|
Anti- TNF-a Treatment (DRESS)
n=22 participants at risk
1. Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF
2. Fill out the case report form
3. Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis
4. Etanercept administration:
The experimental group received the first dose of Etanercept (25 mg) i.v., followed by two doses per week and maintain 2 to 3 weeks
anti-TNF a: 25mg BIW, SC
|
Control Group (DRESS)
n=22 participants at risk
1. Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF
2. Fill out the case report form
3. Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis
4. Drug administration:
The control group of drug delivery: systemic intravenous steroid therapy, the dose is equivalent to prednisolone 1-1.5 mg / kg / day, according to the treatment of 3-4 days gradually decreased dose.
|
|---|---|---|---|---|
|
Infections and infestations
Sepsis
|
4.2%
2/48 • Number of events 2 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
9.3%
4/43 • Number of events 4 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
0.00%
0/22 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
9.1%
2/22 • Number of events 2 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
6.2%
3/48 • Number of events 3 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
11.6%
5/43 • Number of events 5 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
4.5%
1/22 • Number of events 1 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
0.00%
0/22 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
|
Psychiatric disorders
Bipolar disorder
|
2.1%
1/48 • Number of events 1 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
0.00%
0/43 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
0.00%
0/22 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
0.00%
0/22 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
|
Gastrointestinal disorders
Upper GI hemorrhage
|
0.00%
0/48 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
2.3%
1/43 • Number of events 1 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
4.5%
1/22 • Number of events 1 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
9.1%
2/22 • Number of events 2 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
|
Reproductive system and breast disorders
Stridor, vocal cord palsy
|
0.00%
0/48 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
2.3%
1/43 • Number of events 1 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
0.00%
0/22 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
0.00%
0/22 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/48 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
0.00%
0/43 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
0.00%
0/22 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
4.5%
1/22 • Number of events 1 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
Other adverse events
| Measure |
Anti- TNF-a Treatment (SJS/TEN)
n=48 participants at risk
1. Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF
2. Fill out the case report form
3. Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis
4. Etanercept administration:
The experimental group received the first dose of Etanercept (25 mg) i.v., followed by two doses per week and maintain 2 to 3 weeks
anti-TNF a: 25mg BIW, SC
|
Control Group (SJS/TEN)
n=43 participants at risk
1. Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF
2. Fill out the case report form
3. Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis
4. Drug administration:
The control group of drug delivery: systemic intravenous steroid therapy, the dose is equivalent to prednisolone 1-1.5 mg / kg / day, according to the treatment of 3-4 days gradually decreased dose.
|
Anti- TNF-a Treatment (DRESS)
n=22 participants at risk
1. Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF
2. Fill out the case report form
3. Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis
4. Etanercept administration:
The experimental group received the first dose of Etanercept (25 mg) i.v., followed by two doses per week and maintain 2 to 3 weeks
anti-TNF a: 25mg BIW, SC
|
Control Group (DRESS)
n=22 participants at risk
1. Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF
2. Fill out the case report form
3. Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis
4. Drug administration:
The control group of drug delivery: systemic intravenous steroid therapy, the dose is equivalent to prednisolone 1-1.5 mg / kg / day, according to the treatment of 3-4 days gradually decreased dose.
|
|---|---|---|---|---|
|
Vascular disorders
Hypertension
|
12.5%
6/48 • Number of events 6 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
11.6%
5/43 • Number of events 5 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
13.6%
3/22 • Number of events 3 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
9.1%
2/22 • Number of events 2 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
16.7%
8/48 • Number of events 8 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
18.6%
8/43 • Number of events 8 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
18.2%
4/22 • Number of events 4 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
13.6%
3/22 • Number of events 3 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
|
Gastrointestinal disorders
GI hemorrhage (grade 2)
|
2.1%
1/48 • Number of events 1 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
14.0%
6/43 • Number of events 6 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
4.5%
1/22 • Number of events 1 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
13.6%
3/22 • Number of events 3 • one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
|
Additional Information
Drug Hypersensitivity Clinical and Research Center, Laboratory of Dr. Wen-Hung Chung,
Chang Gung Memorial Hospital, Linko
Phone: 886-3-328-1200
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place