Trial Outcomes & Findings for Evaluating Neuroprotection in Aneurysm Coiling Therapy (NCT NCT00728182)
NCT ID: NCT00728182
Last Updated: 2013-10-17
Results Overview
Volume of new ischemic lesions as defined by FLAIR MRI at 12-95 hours postdose
COMPLETED
PHASE2
185 participants
Enrolment, Days 2-4
2013-10-17
Participant Flow
Between September 16, 2008 and March 30, 2011, subjects were recruited to 10 hospitals in Canada and 3 in the United States.
12 subjects were randomized into study but did not receive drug:5 due to do endovascular aneurysm repair, 3 due to inability to obtain a pre-procedure MRI,2 due to pre-procedure ECG showing a QTc interval \> 450 ms, 1 due to a fatal aneurysm rupture before drug, and 1 due to refusal by anesthesiologist to give drug to a subject with severe COPD.
Participant milestones
| Measure |
1 NA-1
20 amino acid peptide that consists of a 9 amino acid domain that inhibits PSD-95 and a 11 amino acid domain than enables the peptide to cross the blood-brain barrier.
NA-1 : single intravenous dose of 2.6 mg/kg of NA-1 administered as a 10-minute infusion
|
2 Placebo
Placebo : single intravenous dose of 2.6 mg/kg of placebo administered as a 10-minute infusion
|
|---|---|---|
|
Overall Study
STARTED
|
92
|
93
|
|
Overall Study
COMPLETED
|
89
|
90
|
|
Overall Study
NOT COMPLETED
|
3
|
3
|
Reasons for withdrawal
| Measure |
1 NA-1
20 amino acid peptide that consists of a 9 amino acid domain that inhibits PSD-95 and a 11 amino acid domain than enables the peptide to cross the blood-brain barrier.
NA-1 : single intravenous dose of 2.6 mg/kg of NA-1 administered as a 10-minute infusion
|
2 Placebo
Placebo : single intravenous dose of 2.6 mg/kg of placebo administered as a 10-minute infusion
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
2
|
0
|
|
Overall Study
Death
|
0
|
2
|
|
Overall Study
Protocol Noncompliance
|
0
|
1
|
Baseline Characteristics
Evaluating Neuroprotection in Aneurysm Coiling Therapy
Baseline characteristics by cohort
| Measure |
1 NA-1
n=92 Participants
20 amino acid peptide that consists of a 9 amino acid domain that inhibits PSD-95 and a 11 amino acid domain than enables the peptide to cross the blood-brain barrier.
NA-1 : single intravenous dose of 2.6 mg/kg of NA-1 administered as a 10-minute infusion
|
2 Placebo
n=93 Participants
Placebo : single intravenous dose of 2.6 mg/kg of placebo administered as a 10-minute infusion
|
Total
n=185 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
70 Participants
n=5 Participants
|
78 Participants
n=7 Participants
|
148 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
22 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
|
Age Continuous
|
57.72 years
STANDARD_DEVIATION 10.6 • n=5 Participants
|
56.05 years
STANDARD_DEVIATION 10.3 • n=7 Participants
|
56.88 years
STANDARD_DEVIATION 10.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
64 Participants
n=5 Participants
|
68 Participants
n=7 Participants
|
132 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
28 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
12 participants
n=5 Participants
|
15 participants
n=7 Participants
|
27 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
80 participants
n=5 Participants
|
78 participants
n=7 Participants
|
158 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Enrolment, Days 2-4Population: All study patients who received study drug and an analyzable MRI at 12-95 hours postdose.
Volume of new ischemic lesions as defined by FLAIR MRI at 12-95 hours postdose
Outcome measures
| Measure |
1 NA-1
n=91 Participants
20 amino acid peptide that consists of a 9 amino acid domain that inhibits PSD-95 and a 11 amino acid domain than enables the peptide to cross the blood-brain barrier.
NA-1 : single intravenous dose of 2.6 mg/kg of NA-1 administered as a 10-minute infusion
|
2 Placebo
n=93 Participants
Placebo : single intravenous dose of 2.6 mg/kg of placebo administered as a 10-minute infusion
|
|---|---|---|
|
Volume of New FLAIR Lesions(MRI)
|
915 mm^3
Standard Deviation 5598
|
477 mm^3
Standard Deviation 1611
|
SECONDARY outcome
Timeframe: Enrolment, Day 2-4Population: All patients who received study drug and an analyzable MRI at 12-95 hours postdose.
Number of new ischemic lesions as defined by DWI MRI at 12-95 hours postdose.
Outcome measures
| Measure |
1 NA-1
n=91 Participants
20 amino acid peptide that consists of a 9 amino acid domain that inhibits PSD-95 and a 11 amino acid domain than enables the peptide to cross the blood-brain barrier.
NA-1 : single intravenous dose of 2.6 mg/kg of NA-1 administered as a 10-minute infusion
|
2 Placebo
n=93 Participants
Placebo : single intravenous dose of 2.6 mg/kg of placebo administered as a 10-minute infusion
|
|---|---|---|
|
Number of New DWI Lesions (MRI)
|
4.1 Lesions
Standard Deviation 6.8
|
7.3 Lesions
Standard Deviation 12.6
|
SECONDARY outcome
Timeframe: Enrolment, Days 2-4Population: All patients who received study drug and an analyzable MRI scan at 12-95 hours postdose.
Number of new ischemic lesions as defined by FLAIR MRI at 12-95 hours postdose.
Outcome measures
| Measure |
1 NA-1
n=91 Participants
20 amino acid peptide that consists of a 9 amino acid domain that inhibits PSD-95 and a 11 amino acid domain than enables the peptide to cross the blood-brain barrier.
NA-1 : single intravenous dose of 2.6 mg/kg of NA-1 administered as a 10-minute infusion
|
2 Placebo
n=93 Participants
Placebo : single intravenous dose of 2.6 mg/kg of placebo administered as a 10-minute infusion
|
|---|---|---|
|
Number of New FLAIR Lesions (MRI)
|
3.0 Lesions
Standard Deviation 4.4
|
4.8 Lesions
Standard Deviation 7.7
|
SECONDARY outcome
Timeframe: Enrolment, Days 2-4Population: All patients who received study drug and an analyzable MRI at 12-95 hours postdose.
Volume of new DWI lesions as defined by MRI at 12-95 hours postdose.
Outcome measures
| Measure |
1 NA-1
n=91 Participants
20 amino acid peptide that consists of a 9 amino acid domain that inhibits PSD-95 and a 11 amino acid domain than enables the peptide to cross the blood-brain barrier.
NA-1 : single intravenous dose of 2.6 mg/kg of NA-1 administered as a 10-minute infusion
|
2 Placebo
n=93 Participants
Placebo : single intravenous dose of 2.6 mg/kg of placebo administered as a 10-minute infusion
|
|---|---|---|
|
Volume of New DWI Lesions (MRI)
|
966 mm^3
Standard Deviation 5266
|
645 mm^3
Standard Deviation 1382
|
SECONDARY outcome
Timeframe: Enrolment, Day 30Population: All patients who received study drug and outcome assessment at Day 30.
The NIHSS is a standardized neurological method to measure disability and recovery after stroke. Scores range from 0 to 42, with higher scores indicating increasing severity. Scores were dichotomized into 0-1 (good outcome) versus 2 or above. The number of participants scoring 0-1 on the NIHSS at Day 30 was compared for both groups.
Outcome measures
| Measure |
1 NA-1
n=92 Participants
20 amino acid peptide that consists of a 9 amino acid domain that inhibits PSD-95 and a 11 amino acid domain than enables the peptide to cross the blood-brain barrier.
NA-1 : single intravenous dose of 2.6 mg/kg of NA-1 administered as a 10-minute infusion
|
2 Placebo
n=93 Participants
Placebo : single intravenous dose of 2.6 mg/kg of placebo administered as a 10-minute infusion
|
|---|---|---|
|
National Institutes of Health Stroke Scale (NIHSS).
|
86 No. of participants with NIHSS 0-1
Interval 0.9 to 1.1
|
83 No. of participants with NIHSS 0-1
Interval 0.9 to 1.1
|
SECONDARY outcome
Timeframe: Enrolment, Day 30Population: All patients who received study drug and an outcome assessment at Day 30
The mRS is a measure of global disability that has been widely applied for evaluating recovery from stroke. Scores range from 0 to 6, with higher scores indicating greater disability. A score of 0 indicates no residual symptoms; 1 = no significant disability/able to carry out all usual activities, despite some symptoms; 2 = slight disability; 3 = moderate disability; 4 = moderately severe disability; 5 = severe disability; 6 = death. The number of participants scoring 0-2 on the mRS at Day 30 was compared in both treatment groups.
Outcome measures
| Measure |
1 NA-1
n=92 Participants
20 amino acid peptide that consists of a 9 amino acid domain that inhibits PSD-95 and a 11 amino acid domain than enables the peptide to cross the blood-brain barrier.
NA-1 : single intravenous dose of 2.6 mg/kg of NA-1 administered as a 10-minute infusion
|
2 Placebo
n=93 Participants
Placebo : single intravenous dose of 2.6 mg/kg of placebo administered as a 10-minute infusion
|
|---|---|---|
|
Modified Rankin Scale (mRS).
|
86 No. of participants with mRS 0-2
Interval 0.9 to 1.1
|
87 No. of participants with mRS 0-2
Interval 0.9 to 1.1
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Enrolment, Days 2-4Population: All subjects who entered the study with a ruptured aneurysm, who received study drug and an analyzable MRI at 12-95 hours postdose.
Volume of new ischemic lesions as defined by FLAIR MRI at 12-95 hours postdose (pre-specified subgroup analysis)
Outcome measures
| Measure |
1 NA-1
n=18 Participants
20 amino acid peptide that consists of a 9 amino acid domain that inhibits PSD-95 and a 11 amino acid domain than enables the peptide to cross the blood-brain barrier.
NA-1 : single intravenous dose of 2.6 mg/kg of NA-1 administered as a 10-minute infusion
|
2 Placebo
n=19 Participants
Placebo : single intravenous dose of 2.6 mg/kg of placebo administered as a 10-minute infusion
|
|---|---|---|
|
Volume of New FLAIR Lesions (MRI) - Ruptured Aneurysm Subjects
|
205 mm^3
Standard Deviation 495
|
1575 mm^3
Standard Deviation 3229
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Enrolment, Day 2-4Population: All subjects who entered the study with a ruptured aneurysm, who received study drug and an analyzable MRI at 12-95 hours postdose.
Number of new ischemic lesions as defined by DWI MRI at 12-95 hours postdose(pre-specified subgroup analysis)
Outcome measures
| Measure |
1 NA-1
n=18 Participants
20 amino acid peptide that consists of a 9 amino acid domain that inhibits PSD-95 and a 11 amino acid domain than enables the peptide to cross the blood-brain barrier.
NA-1 : single intravenous dose of 2.6 mg/kg of NA-1 administered as a 10-minute infusion
|
2 Placebo
n=19 Participants
Placebo : single intravenous dose of 2.6 mg/kg of placebo administered as a 10-minute infusion
|
|---|---|---|
|
Number of New DWI Lesions (MRI) - Ruptured Aneuryms Subjects
|
3.4 Lesions
Standard Deviation 5.9
|
9.47 Lesions
Standard Deviation 11.6
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Enrolment, Day 2-4Population: All subjects who entered the study with a ruptured aneurysm, who received study drug and an analyzable MRI at 12-95 hours postdose.
Number of new ischemic lesions as defined by FLAIR MRI at 12-95 hours postdose(pre-specified subgroup analysis)
Outcome measures
| Measure |
1 NA-1
n=18 Participants
20 amino acid peptide that consists of a 9 amino acid domain that inhibits PSD-95 and a 11 amino acid domain than enables the peptide to cross the blood-brain barrier.
NA-1 : single intravenous dose of 2.6 mg/kg of NA-1 administered as a 10-minute infusion
|
2 Placebo
n=19 Participants
Placebo : single intravenous dose of 2.6 mg/kg of placebo administered as a 10-minute infusion
|
|---|---|---|
|
Number of New FLAIR Lesions (MRI) - Ruptured Aneurysm Subjects
|
2.4 Lesions
Standard Deviation 4.7
|
6.58 Lesions
Standard Deviation 7.5
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Enrolment, Day 2-4Population: All subjects who entered the study with a ruptured aneurysm, who received study drug and an analyzable MRI at 12-95 hours postdose.
Volume of new DWI lesions as defined by MRI at 12-95 hours postdose(pre-specified subgroup analysis)
Outcome measures
| Measure |
1 NA-1
n=18 Participants
20 amino acid peptide that consists of a 9 amino acid domain that inhibits PSD-95 and a 11 amino acid domain than enables the peptide to cross the blood-brain barrier.
NA-1 : single intravenous dose of 2.6 mg/kg of NA-1 administered as a 10-minute infusion
|
2 Placebo
n=19 Participants
Placebo : single intravenous dose of 2.6 mg/kg of placebo administered as a 10-minute infusion
|
|---|---|---|
|
Volume of New DWI Lesions (MRI) - Ruptured Aneurysm Subjects
|
277 mm^3
Standard Deviation 528
|
1373 mm^3
Standard Deviation 2267
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Enrolment, Day 30Population: All subjects who entered the study with a ruptured aneurysm, who received study drug and outcome assessment at Day 30.
The NIHSS is a standardized neurological method to measure disability and recovery after stroke. Scores range from 0 to 42, with higher scores indicating increasing severity. Scores were dichotomized into 0-1 (good outcome) versus 2 or above. The number of participants scoring 0-1 on the NIHSS at Day 30 was compared for participants with ruptured aneurysms in both treatment groups(pre-specified subgroup analysis).
Outcome measures
| Measure |
1 NA-1
n=18 Participants
20 amino acid peptide that consists of a 9 amino acid domain that inhibits PSD-95 and a 11 amino acid domain than enables the peptide to cross the blood-brain barrier.
NA-1 : single intravenous dose of 2.6 mg/kg of NA-1 administered as a 10-minute infusion
|
2 Placebo
n=19 Participants
Placebo : single intravenous dose of 2.6 mg/kg of placebo administered as a 10-minute infusion
|
|---|---|---|
|
National Institutes of Health Stroke Scale (NIHSS) - Ruptured Aneurysm Subjects
|
18 No. of participants with NIHSS 0-1
|
13 No. of participants with NIHSS 0-1
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Enrolment, Day 30The mRS is a measure of global disability that has been widely applied for evaluating recovery from stroke. Scores range from 0 to 6, with higher scores indicating greater disability. A score of 0 indicates no residual symptoms; 1 = no significant disability/able to carry out all usual activities, despite some symptoms; 2 = slight disability; 3 = moderate disability; 4 = moderately severe disability; 5 = severe disability; 6 = death. The number of participants scoring 0-2 on the mRS at Day 30 with ruptured aneurysms was compared in both treatment groups(pre-specified subgroup analysis).
Outcome measures
| Measure |
1 NA-1
n=18 Participants
20 amino acid peptide that consists of a 9 amino acid domain that inhibits PSD-95 and a 11 amino acid domain than enables the peptide to cross the blood-brain barrier.
NA-1 : single intravenous dose of 2.6 mg/kg of NA-1 administered as a 10-minute infusion
|
2 Placebo
n=19 Participants
Placebo : single intravenous dose of 2.6 mg/kg of placebo administered as a 10-minute infusion
|
|---|---|---|
|
Modified Rankin Scale (mRS)- Ruptured Aneurysm Subjects
|
17 No. of participants with mRS 0-2
|
14 No. of participants with mRS 0-2
|
Adverse Events
1 NA-1
2 Placebo
Serious adverse events
| Measure |
1 NA-1
n=92 participants at risk
20 amino acid peptide that consists of a 9 amino acid domain that inhibits PSD-95 and a 11 amino acid domain than enables the peptide to cross the blood-brain barrier.
NA-1 : single intravenous dose of 2.6 mg/kg of NA-1 administered as a 10-minute infusion
|
2 Placebo
n=93 participants at risk
Placebo : single intravenous dose of 2.6 mg/kg of placebo administered as a 10-minute infusion
|
|---|---|---|
|
Gastrointestinal disorders
Gastrointestinal
|
0.00%
0/92
|
2.2%
2/93 • Number of events 2
|
|
Injury, poisoning and procedural complications
Procedural complications
|
1.1%
1/92 • Number of events 1
|
2.2%
2/93 • Number of events 2
|
|
Nervous system disorders
Nervous system
|
3.3%
3/92 • Number of events 3
|
9.7%
9/93 • Number of events 14
|
|
Renal and urinary disorders
Genitourinary
|
1.1%
1/92 • Number of events 1
|
1.1%
1/93 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory
|
1.1%
1/92 • Number of events 2
|
1.1%
1/93 • Number of events 2
|
|
Vascular disorders
Vascular
|
3.3%
3/92 • Number of events 3
|
3.2%
3/93 • Number of events 3
|
|
General disorders
Administration site
|
1.1%
1/92 • Number of events 1
|
0.00%
0/93
|
Other adverse events
| Measure |
1 NA-1
n=92 participants at risk
20 amino acid peptide that consists of a 9 amino acid domain that inhibits PSD-95 and a 11 amino acid domain than enables the peptide to cross the blood-brain barrier.
NA-1 : single intravenous dose of 2.6 mg/kg of NA-1 administered as a 10-minute infusion
|
2 Placebo
n=93 participants at risk
Placebo : single intravenous dose of 2.6 mg/kg of placebo administered as a 10-minute infusion
|
|---|---|---|
|
Nervous system disorders
Headache
|
45.7%
42/92 • Number of events 47
|
39.8%
37/93 • Number of events 39
|
|
Gastrointestinal disorders
Nausea
|
35.9%
33/92 • Number of events 33
|
29.0%
27/93 • Number of events 28
|
|
Gastrointestinal disorders
Vomiting
|
13.0%
12/92 • Number of events 12
|
8.6%
8/93 • Number of events 8
|
|
Vascular disorders
Hypotension
|
9.8%
9/92 • Number of events 10
|
6.5%
6/93 • Number of events 6
|
|
Injury, poisoning and procedural complications
Procedural pain
|
2.2%
2/92 • Number of events 2
|
10.8%
10/93 • Number of events 10
|
|
Vascular disorders
Hypertension
|
4.3%
4/92 • Number of events 4
|
7.5%
7/93 • Number of events 7
|
|
Eye disorders
Eye pain
|
1.1%
1/92 • Number of events 1
|
5.4%
5/93 • Number of events 5
|
|
Gastrointestinal disorders
Constipation
|
4.3%
4/92 • Number of events 4
|
7.5%
7/93 • Number of events 7
|
|
General disorders
Fatigue
|
1.1%
1/92 • Number of events 1
|
7.5%
7/93 • Number of events 7
|
|
General disorders
Puncture site pain
|
5.4%
5/92 • Number of events 5
|
5.4%
5/93 • Number of events 5
|
|
Infections and infestations
Urinary tract infection
|
7.6%
7/92 • Number of events 7
|
3.2%
3/93 • Number of events 3
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
4.3%
4/92 • Number of events 4
|
5.4%
5/93 • Number of events 5
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
6.5%
6/92 • Number of events 6
|
4.3%
4/93 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.5%
6/92 • Number of events 6
|
7.5%
7/93 • Number of events 7
|
|
Nervous system disorders
Dizziness
|
6.5%
6/92 • Number of events 6
|
2.2%
2/93 • Number of events 3
|
|
Nervous system disorders
Hypoaesthesia
|
4.3%
4/92 • Number of events 4
|
5.4%
5/93 • Number of events 5
|
|
Psychiatric disorders
Anxiety
|
3.3%
3/92 • Number of events 3
|
7.5%
7/93 • Number of events 8
|
|
Renal and urinary disorders
Haematuria
|
5.4%
5/92 • Number of events 5
|
4.3%
4/93 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
5.4%
5/92 • Number of events 5
|
2.2%
2/93 • Number of events 2
|
|
Vascular disorders
Haematoma
|
6.5%
6/92 • Number of events 6
|
7.5%
7/93 • Number of events 7
|
Additional Information
Roberta Anderson, Vice President of Clinical Development
NoNO Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee The Investigator shall have the right to publish any information after prior submittal to NoNO, where NoNO can request a hold for up to 60 days, provided that no publication shall disclose Proprietary Information other than Data containing the results of the Study. Investigators may not publish in the first 18 months after the close of the trial except within a publication representing all participating clinical sites.
- Publication restrictions are in place
Restriction type: OTHER