Trial Outcomes & Findings for Neuroprotection in Acute Ischemic Stroke (NCT NCT03320018)
NCT ID: NCT03320018
Last Updated: 2023-12-19
Results Overview
rating scale to assess level of functional independence for patients post-stroke. Scores range from 0 (no symptoms) to 6 (dead). mRS scores at 90 days will be classified as favorable or unfavorable based on the baseline NIHSS measured at time of enrollment. Subjects in the lowest baseline severity tertile (NIHSS 5-7) will need to have a 90 day mRS score of 0 to be considered to have a favorable outcome. Subjects with baseline NIHSS 8-14 will need a 90 day mRS score 0-1 to be considered to have a favorable outcome; those with baseline NIHSS 15-25 will need a 90 day mRS score 0-2 to be considered to have a favorable outcome.
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
15 participants
Primary outcome timeframe
90 days
Results posted on
2023-12-19
Participant Flow
Of the 15 enrolled participants, 14 met inclusion exclusion criteria and were randomized to treatment.
Participant milestones
| Measure |
Hydrogen/Minocycline
Hydrogen will be infused into aqueous solution (normal saline or water) at as high a concentration as possible (saturation = 1.6 ppm), and administered intravenously or orally respectively, TID for 3 days.
Similarly, Minocycline will be administered either i.v. or p.o. once daily for 5 days.
Hydrogen: Hydrogen will be infused into bags of normal saline solution and administered intravenously, or hydrogen generating tablets will be dissolved into water for the patient to drink, as the patient's condition permits. This will be administered TID for 3 days.
Minocycline: Minocycline 200 mg will be mixed with normal saline and given by i.v. administration, or provided as capsules for the patient to swallow, q 24 hours for 5 days.
Once patients regain the ability to swallow capsules, minocycline will be given orally in capsule form (2 capsules of 100 mg each), administered once daily for the remainder of the 5 day period.
|
Placebo Hydrogen/Placebo Minocycline
Normal saline will be substituted for both Hydrogen and Minocycline for intravenous administration. Water will be substituted for hydrogen when administered p.o., and placebo capsules will be substituted for minocycline.
Placebo Hydrogen: Normal saline solution will be administered intravenously, in place of hydrogen solution.
Placebo tablets will be dissolved into water for the patient to drink, as the patient's condition permits. This will be administered TID for 3 days.
Placebo Minocycline: Normal saline solution or placebo capsule will be administered i.v. or p.o. respectively, in place of minocycline.
|
|---|---|---|
|
Treatment Period
STARTED
|
6
|
8
|
|
Treatment Period
COMPLETED
|
5
|
8
|
|
Treatment Period
NOT COMPLETED
|
1
|
0
|
|
Day 45 Follow up
STARTED
|
5
|
8
|
|
Day 45 Follow up
COMPLETED
|
5
|
8
|
|
Day 45 Follow up
NOT COMPLETED
|
0
|
0
|
|
Day 90 Follow up
STARTED
|
5
|
8
|
|
Day 90 Follow up
COMPLETED
|
5
|
7
|
|
Day 90 Follow up
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Hydrogen/Minocycline
Hydrogen will be infused into aqueous solution (normal saline or water) at as high a concentration as possible (saturation = 1.6 ppm), and administered intravenously or orally respectively, TID for 3 days.
Similarly, Minocycline will be administered either i.v. or p.o. once daily for 5 days.
Hydrogen: Hydrogen will be infused into bags of normal saline solution and administered intravenously, or hydrogen generating tablets will be dissolved into water for the patient to drink, as the patient's condition permits. This will be administered TID for 3 days.
Minocycline: Minocycline 200 mg will be mixed with normal saline and given by i.v. administration, or provided as capsules for the patient to swallow, q 24 hours for 5 days.
Once patients regain the ability to swallow capsules, minocycline will be given orally in capsule form (2 capsules of 100 mg each), administered once daily for the remainder of the 5 day period.
|
Placebo Hydrogen/Placebo Minocycline
Normal saline will be substituted for both Hydrogen and Minocycline for intravenous administration. Water will be substituted for hydrogen when administered p.o., and placebo capsules will be substituted for minocycline.
Placebo Hydrogen: Normal saline solution will be administered intravenously, in place of hydrogen solution.
Placebo tablets will be dissolved into water for the patient to drink, as the patient's condition permits. This will be administered TID for 3 days.
Placebo Minocycline: Normal saline solution or placebo capsule will be administered i.v. or p.o. respectively, in place of minocycline.
|
|---|---|---|
|
Treatment Period
Withdrawal by Subject
|
1
|
0
|
|
Day 90 Follow up
Death
|
0
|
1
|
Baseline Characteristics
Neuroprotection in Acute Ischemic Stroke
Baseline characteristics by cohort
| Measure |
Hydrogen/Minocycline
n=6 Participants
Hydrogen will be infused into aqueous solution (normal saline or water) at as high a concentration as possible (saturation = 1.6 ppm), and administered intravenously or orally respectively, TID for 3 days.
Similarly, Minocycline will be administered either i.v. or p.o. once daily for 5 days.
Hydrogen: Hydrogen will be infused into bags of normal saline solution and administered intravenously, or hydrogen generating tablets will be dissolved into water for the patient to drink, as the patient's condition permits. This will be administered TID for 3 days.
Minocycline: Minocycline 200 mg will be mixed with normal saline and given by i.v. administration, or provided as capsules for the patient to swallow, q 24 hours for 5 days.
Once patients regain the ability to swallow capsules, minocycline will be given orally in capsule form (2 capsules of 100 mg each), administered once daily for the remainder of the 5 day period.
|
Placebo Hydrogen/Placebo Minocycline
n=8 Participants
Normal saline will be substituted for both Hydrogen and Minocycline for intravenous administration. Water will be substituted for hydrogen when administered p.o., and placebo capsules will be substituted for minocycline.
Placebo Hydrogen: Normal saline solution will be administered intravenously, in place of hydrogen solution.
Placebo tablets will be dissolved into water for the patient to drink, as the patient's condition permits. This will be administered TID for 3 days.
Placebo Minocycline: Normal saline solution or placebo capsule will be administered i.v. or p.o. respectively, in place of minocycline.
|
Total
n=14 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
74.17 years
STANDARD_DEVIATION 12.32 • n=5 Participants
|
65.13 years
STANDARD_DEVIATION 13.92 • n=7 Participants
|
69.00 years
STANDARD_DEVIATION 13.58 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=5 Participants
|
8 participants
n=7 Participants
|
14 participants
n=5 Participants
|
|
NIH Stroke Scale (NIHSS)
|
8.5 units on a scale
n=5 Participants
|
12.5 units on a scale
n=7 Participants
|
9.5 units on a scale
n=5 Participants
|
PRIMARY outcome
Timeframe: 90 daysPopulation: Subjects lost to follow are considered to have an unfavorable outcome.
rating scale to assess level of functional independence for patients post-stroke. Scores range from 0 (no symptoms) to 6 (dead). mRS scores at 90 days will be classified as favorable or unfavorable based on the baseline NIHSS measured at time of enrollment. Subjects in the lowest baseline severity tertile (NIHSS 5-7) will need to have a 90 day mRS score of 0 to be considered to have a favorable outcome. Subjects with baseline NIHSS 8-14 will need a 90 day mRS score 0-1 to be considered to have a favorable outcome; those with baseline NIHSS 15-25 will need a 90 day mRS score 0-2 to be considered to have a favorable outcome.
Outcome measures
| Measure |
Hydrogen/Minocycline
n=6 Participants
Hydrogen will be infused into aqueous solution (normal saline or water) at as high a concentration as possible (saturation = 1.6 ppm), and administered intravenously or orally respectively, TID for 3 days.
Similarly, Minocycline will be administered either i.v. or p.o. once daily for 5 days.
Hydrogen: Hydrogen will be infused into bags of normal saline solution and administered intravenously, or hydrogen generating tablets will be dissolved into water for the patient to drink, as the patient's condition permits. This will be administered TID for 3 days.
Minocycline: Minocycline 200 mg will be mixed with normal saline and given by i.v. administration, or provided as capsules for the patient to swallow, q 24 hours for 5 days.
Once patients regain the ability to swallow capsules, minocycline will be given orally in capsule form (2 capsules of 100 mg each), administered once daily for the remainder of the 5 day period.
|
Placebo Hydrogen/Placebo Minocycline
n=8 Participants
Normal saline will be substituted for both Hydrogen and Minocycline for intravenous administration. Water will be substituted for hydrogen when administered p.o., and placebo capsules will be substituted for minocycline.
Placebo Hydrogen: Normal saline solution will be administered intravenously, in place of hydrogen solution.
Placebo tablets will be dissolved into water for the patient to drink, as the patient's condition permits. This will be administered TID for 3 days.
Placebo Minocycline: Normal saline solution or placebo capsule will be administered i.v. or p.o. respectively, in place of minocycline.
|
|---|---|---|
|
Number of Participants With Favorable Outcome on the Simplified Modified Rankin Scale (sMRSq)
Unfavorable outcome
|
5 participants
|
7 participants
|
|
Number of Participants With Favorable Outcome on the Simplified Modified Rankin Scale (sMRSq)
Favorable outcome
|
1 participants
|
1 participants
|
SECONDARY outcome
Timeframe: 45 daysrating scale to assess level of functional independence for patients post-stroke. Scores range from 0 (no symptoms) to 6 (dead).
Outcome measures
| Measure |
Hydrogen/Minocycline
n=5 Participants
Hydrogen will be infused into aqueous solution (normal saline or water) at as high a concentration as possible (saturation = 1.6 ppm), and administered intravenously or orally respectively, TID for 3 days.
Similarly, Minocycline will be administered either i.v. or p.o. once daily for 5 days.
Hydrogen: Hydrogen will be infused into bags of normal saline solution and administered intravenously, or hydrogen generating tablets will be dissolved into water for the patient to drink, as the patient's condition permits. This will be administered TID for 3 days.
Minocycline: Minocycline 200 mg will be mixed with normal saline and given by i.v. administration, or provided as capsules for the patient to swallow, q 24 hours for 5 days.
Once patients regain the ability to swallow capsules, minocycline will be given orally in capsule form (2 capsules of 100 mg each), administered once daily for the remainder of the 5 day period.
|
Placebo Hydrogen/Placebo Minocycline
n=8 Participants
Normal saline will be substituted for both Hydrogen and Minocycline for intravenous administration. Water will be substituted for hydrogen when administered p.o., and placebo capsules will be substituted for minocycline.
Placebo Hydrogen: Normal saline solution will be administered intravenously, in place of hydrogen solution.
Placebo tablets will be dissolved into water for the patient to drink, as the patient's condition permits. This will be administered TID for 3 days.
Placebo Minocycline: Normal saline solution or placebo capsule will be administered i.v. or p.o. respectively, in place of minocycline.
|
|---|---|---|
|
Simplified Modified Rankin Scale (sMRSq)
|
2.8 score on a scale
Standard Deviation 1.6
|
3.4 score on a scale
Standard Deviation 1.3
|
SECONDARY outcome
Timeframe: 90 daysPopulation: Per protocol the 90 day follow up is done either in person or by phone. The NIHSS is administered subjects who are able to be seen in-person for the follow-up visit.
15-item neurologic examination scale for severity of stroke. Ratings for each item are scored with 3 to 5 grades. A total NIHSS of 0 is normal; 1-4 is considered a minor stroke; 5-15 moderate; 16-20 moderate to severe; and 21-42 severe.
Outcome measures
| Measure |
Hydrogen/Minocycline
n=2 Participants
Hydrogen will be infused into aqueous solution (normal saline or water) at as high a concentration as possible (saturation = 1.6 ppm), and administered intravenously or orally respectively, TID for 3 days.
Similarly, Minocycline will be administered either i.v. or p.o. once daily for 5 days.
Hydrogen: Hydrogen will be infused into bags of normal saline solution and administered intravenously, or hydrogen generating tablets will be dissolved into water for the patient to drink, as the patient's condition permits. This will be administered TID for 3 days.
Minocycline: Minocycline 200 mg will be mixed with normal saline and given by i.v. administration, or provided as capsules for the patient to swallow, q 24 hours for 5 days.
Once patients regain the ability to swallow capsules, minocycline will be given orally in capsule form (2 capsules of 100 mg each), administered once daily for the remainder of the 5 day period.
|
Placebo Hydrogen/Placebo Minocycline
n=2 Participants
Normal saline will be substituted for both Hydrogen and Minocycline for intravenous administration. Water will be substituted for hydrogen when administered p.o., and placebo capsules will be substituted for minocycline.
Placebo Hydrogen: Normal saline solution will be administered intravenously, in place of hydrogen solution.
Placebo tablets will be dissolved into water for the patient to drink, as the patient's condition permits. This will be administered TID for 3 days.
Placebo Minocycline: Normal saline solution or placebo capsule will be administered i.v. or p.o. respectively, in place of minocycline.
|
|---|---|---|
|
NIH Stroke Scale (NIHSS)
|
4 score on a scale
Standard Deviation 4.2
|
7.5 score on a scale
Standard Deviation 3.5
|
Adverse Events
Hydrogen/Minocycline
Serious events: 2 serious events
Other events: 5 other events
Deaths: 0 deaths
Placebo Hydrogen/Placebo Minocycline
Serious events: 1 serious events
Other events: 5 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Hydrogen/Minocycline
n=6 participants at risk
Hydrogen will be infused into aqueous solution (normal saline or water) at as high a concentration as possible (saturation = 1.6 ppm), and administered intravenously or orally respectively, TID for 3 days.
Similarly, Minocycline will be administered either i.v. or p.o. once daily for 5 days.
Hydrogen: Hydrogen will be infused into bags of normal saline solution and administered intravenously, or hydrogen generating tablets will be dissolved into water for the patient to drink, as the patient's condition permits. This will be administered TID for 3 days.
Minocycline: Minocycline 200 mg will be mixed with normal saline and given by i.v. administration, or provided as capsules for the patient to swallow, q 24 hours for 5 days.
Once patients regain the ability to swallow capsules, minocycline will be given orally in capsule form (2 capsules of 100 mg each), administered once daily for the remainder of the 5 day period.
|
Placebo Hydrogen/Placebo Minocycline
n=8 participants at risk
Normal saline will be substituted for both Hydrogen and Minocycline for intravenous administration. Water will be substituted for hydrogen when administered p.o., and placebo capsules will be substituted for minocycline.
Placebo Hydrogen: Normal saline solution will be administered intravenously, in place of hydrogen solution.
Placebo tablets will be dissolved into water for the patient to drink, as the patient's condition permits. This will be administered TID for 3 days.
Placebo Minocycline: Normal saline solution or placebo capsule will be administered i.v. or p.o. respectively, in place of minocycline.
|
|---|---|---|
|
Cardiac disorders
stroke
|
16.7%
1/6 • Number of events 1 • 90 days
|
0.00%
0/8 • 90 days
|
|
Cardiac disorders
bradycardia and syncope
|
16.7%
1/6 • Number of events 2 • 90 days
|
0.00%
0/8 • 90 days
|
|
Gastrointestinal disorders
hematochezia
|
0.00%
0/6 • 90 days
|
12.5%
1/8 • Number of events 1 • 90 days
|
|
Cardiac disorders
thrombus
|
16.7%
1/6 • Number of events 1 • 90 days
|
12.5%
1/8 • Number of events 1 • 90 days
|
Other adverse events
| Measure |
Hydrogen/Minocycline
n=6 participants at risk
Hydrogen will be infused into aqueous solution (normal saline or water) at as high a concentration as possible (saturation = 1.6 ppm), and administered intravenously or orally respectively, TID for 3 days.
Similarly, Minocycline will be administered either i.v. or p.o. once daily for 5 days.
Hydrogen: Hydrogen will be infused into bags of normal saline solution and administered intravenously, or hydrogen generating tablets will be dissolved into water for the patient to drink, as the patient's condition permits. This will be administered TID for 3 days.
Minocycline: Minocycline 200 mg will be mixed with normal saline and given by i.v. administration, or provided as capsules for the patient to swallow, q 24 hours for 5 days.
Once patients regain the ability to swallow capsules, minocycline will be given orally in capsule form (2 capsules of 100 mg each), administered once daily for the remainder of the 5 day period.
|
Placebo Hydrogen/Placebo Minocycline
n=8 participants at risk
Normal saline will be substituted for both Hydrogen and Minocycline for intravenous administration. Water will be substituted for hydrogen when administered p.o., and placebo capsules will be substituted for minocycline.
Placebo Hydrogen: Normal saline solution will be administered intravenously, in place of hydrogen solution.
Placebo tablets will be dissolved into water for the patient to drink, as the patient's condition permits. This will be administered TID for 3 days.
Placebo Minocycline: Normal saline solution or placebo capsule will be administered i.v. or p.o. respectively, in place of minocycline.
|
|---|---|---|
|
Eye disorders
twitching with anisocoria
|
0.00%
0/6 • 90 days
|
12.5%
1/8 • Number of events 1 • 90 days
|
|
Skin and subcutaneous tissue disorders
Wound complication
|
0.00%
0/6 • 90 days
|
12.5%
1/8 • Number of events 1 • 90 days
|
|
Skin and subcutaneous tissue disorders
skin redness and swelling
|
0.00%
0/6 • 90 days
|
12.5%
1/8 • Number of events 1 • 90 days
|
|
Renal and urinary disorders
hematuria
|
0.00%
0/6 • 90 days
|
12.5%
1/8 • Number of events 1 • 90 days
|
|
Cardiac disorders
hypotension
|
16.7%
1/6 • Number of events 1 • 90 days
|
12.5%
1/8 • Number of events 2 • 90 days
|
|
Skin and subcutaneous tissue disorders
rash
|
16.7%
1/6 • Number of events 1 • 90 days
|
25.0%
2/8 • Number of events 2 • 90 days
|
|
Blood and lymphatic system disorders
Hypotension
|
0.00%
0/6 • 90 days
|
12.5%
1/8 • Number of events 1 • 90 days
|
|
Renal and urinary disorders
urinary tract infection
|
0.00%
0/6 • 90 days
|
12.5%
1/8 • Number of events 1 • 90 days
|
|
Reproductive system and breast disorders
vaginal bleeding
|
0.00%
0/6 • 90 days
|
12.5%
1/8 • Number of events 1 • 90 days
|
|
Cardiac disorders
bradycardia
|
16.7%
1/6 • Number of events 1 • 90 days
|
0.00%
0/8 • 90 days
|
|
Blood and lymphatic system disorders
ecchymotic penis and scrotum
|
0.00%
0/6 • 90 days
|
12.5%
1/8 • Number of events 1 • 90 days
|
|
Respiratory, thoracic and mediastinal disorders
pulmonary congestion
|
0.00%
0/6 • 90 days
|
12.5%
1/8 • Number of events 1 • 90 days
|
|
Cardiac disorders
petechial hemorrhagic stroke conversion
|
16.7%
1/6 • Number of events 1 • 90 days
|
0.00%
0/8 • 90 days
|
|
Nervous system disorders
headache
|
16.7%
1/6 • Number of events 1 • 90 days
|
12.5%
1/8 • Number of events 1 • 90 days
|
|
Musculoskeletal and connective tissue disorders
inflammation in foot
|
0.00%
0/6 • 90 days
|
12.5%
1/8 • Number of events 1 • 90 days
|
|
Skin and subcutaneous tissue disorders
black lesion in foot
|
16.7%
1/6 • Number of events 1 • 90 days
|
0.00%
0/8 • 90 days
|
|
Renal and urinary disorders
hyponatremia
|
16.7%
1/6 • Number of events 1 • 90 days
|
0.00%
0/8 • 90 days
|
|
Renal and urinary disorders
increased BUN/creatinine
|
16.7%
1/6 • Number of events 1 • 90 days
|
0.00%
0/8 • 90 days
|
|
Gastrointestinal disorders
diarrhea
|
16.7%
1/6 • Number of events 1 • 90 days
|
0.00%
0/8 • 90 days
|
|
General disorders
nausea
|
0.00%
0/6 • 90 days
|
12.5%
1/8 • Number of events 1 • 90 days
|
|
Nervous system disorders
decreased sensation
|
0.00%
0/6 • 90 days
|
12.5%
1/8 • Number of events 1 • 90 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place