Trial Outcomes & Findings for The Effects of Tiopronin on 3-Aminopropanal Level & Neurologic Outcome After Aneurysmal Subarachnoid Hemorrhage (NCT NCT01095731)
NCT ID: NCT01095731
Last Updated: 2025-10-29
Results Overview
The level of 3-aminopropanal (3-AP) in cerebrospinal fluid (CSF) measured in nmol/mL. CSF samples taken as a standard of care.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
60 participants
Primary outcome timeframe
Day 7
Results posted on
2025-10-29
Participant Flow
60 participants enrolled and one withdrew consent prior to randomization, resulting in allocation of 59 participants.
Participant milestones
| Measure |
Tiopronin, Hunt Hess Grade I-V
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Tiopronin: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
Sugar Pill, Hunt Hess Grade I-V
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Placebo: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
|---|---|---|
|
Overall Study
STARTED
|
30
|
29
|
|
Overall Study
COMPLETED
|
29
|
27
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
Tiopronin, Hunt Hess Grade I-V
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Tiopronin: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
Sugar Pill, Hunt Hess Grade I-V
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Placebo: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
|---|---|---|
|
Overall Study
Protocol Violation
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
The Effects of Tiopronin on 3-Aminopropanal Level & Neurologic Outcome After Aneurysmal Subarachnoid Hemorrhage
Baseline characteristics by cohort
| Measure |
Tiopronin, Hunt Hess Grade I-V
n=30 Participants
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Tiopronin: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
Sugar Pill, Hunt Hess Grade I-V
n=29 Participants
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Placebo: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
Total
n=59 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
40 - 80 years
|
30 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
59 Participants
n=5 Participants
|
|
Sex/Gender, Customized
Female
|
17 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
|
Sex/Gender, Customized
Male
|
12 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Sex/Gender, Customized
Unknown/Not reported
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
13 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
8 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Unknown/Not reported
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
30 participants
n=5 Participants
|
29 participants
n=7 Participants
|
59 participants
n=5 Participants
|
|
Diabetes Mellitus
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Smoker
|
18 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 7Population: CSF samples were successfully collected on day 7 in 12 and 13 participants in the tiopronin and sugar pill arms, respectively.
The level of 3-aminopropanal (3-AP) in cerebrospinal fluid (CSF) measured in nmol/mL. CSF samples taken as a standard of care.
Outcome measures
| Measure |
Tiopronin, Hunt Hess Grade I-V
n=12 Participants
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Tiopronin: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
Sugar Pill, Hunt Hess Grade I-V
n=13 Participants
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Placebo: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
|---|---|---|
|
Cerebrospinal Fluid 3-aminopropanal (CSF-3AP) Levels
|
11.1 nmol/mL
Standard Deviation 11.8
|
12.9 nmol/mL
Standard Deviation 17.6
|
SECONDARY outcome
Timeframe: Day 14Population: CSF samples were successfully collected on day 14 in 13 and 9 participants in the tiopronin and sugar pill arms respectively.
The level of 3-aminopropanal (3-AP) in cerebrospinal fluid (CSF) measured in nmol/mL. CSF samples taken as a standard of care.
Outcome measures
| Measure |
Tiopronin, Hunt Hess Grade I-V
n=13 Participants
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Tiopronin: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
Sugar Pill, Hunt Hess Grade I-V
n=9 Participants
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Placebo: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
|---|---|---|
|
Cerebrospinal Fluid 3-aminopropanal (CSF-3AP) Levels
|
14.7 nmol/mL
Standard Deviation 18.8
|
9.9 nmol/mL
Standard Deviation 10.3
|
SECONDARY outcome
Timeframe: At time of discharge, approximately Day 14The Modified Rankin Score (mRS) is a disability scale with possible scores ranging from 0 (no symptoms) to 5 (severe disability).
Outcome measures
| Measure |
Tiopronin, Hunt Hess Grade I-V
n=29 Participants
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Tiopronin: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
Sugar Pill, Hunt Hess Grade I-V
n=27 Participants
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Placebo: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
|---|---|---|
|
Modified Rankin Score (mRS) at Discharge
|
4 score on a scale
Interval 2.0 to 5.0
|
4 score on a scale
Interval 3.0 to 5.0
|
SECONDARY outcome
Timeframe: 3 monthsThe Modified Rankin Score (mRS) is a disability scale with possible scores ranging from 0 (no symptoms) to 5 (severe disability).
Outcome measures
| Measure |
Tiopronin, Hunt Hess Grade I-V
n=29 Participants
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Tiopronin: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
Sugar Pill, Hunt Hess Grade I-V
n=27 Participants
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Placebo: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
|---|---|---|
|
Modified Rankin Score (mRS) at 3 Months
|
3 score on a scale
Interval 2.0 to 4.0
|
2 score on a scale
Interval 1.0 to 4.0
|
SECONDARY outcome
Timeframe: 12 monthsThe Modified Rankin Score (mRS) is a disability scale with possible scores ranging from 0 (no symptoms) to 5 (severe disability).
Outcome measures
| Measure |
Tiopronin, Hunt Hess Grade I-V
n=29 Participants
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Tiopronin: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
Sugar Pill, Hunt Hess Grade I-V
n=27 Participants
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Placebo: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
|---|---|---|
|
Modified Rankin Score (mRS) at 12 Months
|
2 score on a scale
Interval 1.0 to 2.0
|
2 score on a scale
Interval 1.0 to 3.0
|
SECONDARY outcome
Timeframe: At time of discharge, approximately Day 14Barthel index is a scale used to measure dependency in performing daily activities. Scores range from 0 (total dependency) to 100 (no dependency). A higher score indicates a better outcome.
Outcome measures
| Measure |
Tiopronin, Hunt Hess Grade I-V
n=29 Participants
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Tiopronin: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
Sugar Pill, Hunt Hess Grade I-V
n=27 Participants
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Placebo: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
|---|---|---|
|
Barthel Index at Discharge
|
37 score on a scale
Standard Deviation 53
|
30 score on a scale
Standard Deviation 38
|
SECONDARY outcome
Timeframe: 3 monthsBarthel index is a scale used to measure dependency in performing daily activities. Scores range from 0 (total dependency) to 100 (no dependency). A higher score indicates a better outcome.
Outcome measures
| Measure |
Tiopronin, Hunt Hess Grade I-V
n=29 Participants
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Tiopronin: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
Sugar Pill, Hunt Hess Grade I-V
n=27 Participants
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Placebo: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
|---|---|---|
|
Barthel Index at 3 Months
|
83 score on a scale
Standard Deviation 33
|
85 score on a scale
Standard Deviation 28
|
SECONDARY outcome
Timeframe: 12 monthsBarthel index is a scale used to measure dependency in performing daily activities. Scores range from 0 (total dependency) to 100 (no dependency). A higher score indicates a better outcome.
Outcome measures
| Measure |
Tiopronin, Hunt Hess Grade I-V
n=29 Participants
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Tiopronin: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
Sugar Pill, Hunt Hess Grade I-V
n=27 Participants
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Placebo: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
|---|---|---|
|
Barthel Index at 12 Months
|
94 score on a scale
Standard Deviation 24
|
98 score on a scale
Standard Deviation 5
|
Adverse Events
Tiopronin, Hunt Hess Grade I-V
Serious events: 6 serious events
Other events: 13 other events
Deaths: 4 deaths
Sugar Pill, Hunt Hess Grade I-V
Serious events: 9 serious events
Other events: 16 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Tiopronin, Hunt Hess Grade I-V
n=29 participants at risk
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Tiopronin: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
Sugar Pill, Hunt Hess Grade I-V
n=27 participants at risk
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Placebo: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
|---|---|---|
|
General disorders
Terminal Extubation (withdrawal of care)
|
6.9%
2/29
|
3.7%
1/27
|
|
Nervous system disorders
Ventriculitis
|
3.4%
1/29
|
0.00%
0/27
|
|
General disorders
Hypoxia
|
3.4%
1/29
|
0.00%
0/27
|
|
General disorders
Cardiopulmonary Arrest
|
0.00%
0/29
|
7.4%
2/27
|
|
Nervous system disorders
Neurological Deterioration
|
3.4%
1/29
|
3.7%
1/27
|
|
General disorders
Acidosis
|
0.00%
0/29
|
3.7%
1/27
|
|
Infections and infestations
Staphylococcus aureus Infection
|
0.00%
0/29
|
3.7%
1/27
|
|
General disorders
Fever
|
3.4%
1/29
|
0.00%
0/27
|
|
General disorders
Prolonged Intubation
|
0.00%
0/29
|
3.7%
1/27
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/29
|
3.7%
1/27
|
|
General disorders
Fever of unknown origin
|
0.00%
0/29
|
3.7%
1/27
|
Other adverse events
| Measure |
Tiopronin, Hunt Hess Grade I-V
n=29 participants at risk
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Tiopronin: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
Sugar Pill, Hunt Hess Grade I-V
n=27 participants at risk
Good Grade (Hunt Hess I-III) and Poor Grade (Hunt Hess IV-V)
Placebo: Dosage will be 1 gram, 3 times daily. Drug dosing will be initiated at time of aSAH confirmation, for a length of 14 days or at hospital discharge.
|
|---|---|---|
|
General disorders
Fever
|
17.2%
5/29
|
18.5%
5/27
|
|
Vascular disorders
Thrombosis
|
3.4%
1/29
|
3.7%
1/27
|
|
Nervous system disorders
Seizure
|
6.9%
2/29
|
3.7%
1/27
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
3.4%
1/29
|
3.7%
1/27
|
|
General disorders
Hypernatremia
|
6.9%
2/29
|
3.7%
1/27
|
|
General disorders
Hyponatremia
|
10.3%
3/29
|
7.4%
2/27
|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome
|
3.4%
1/29
|
3.7%
1/27
|
|
Nervous system disorders
Headache
|
0.00%
0/29
|
3.7%
1/27
|
|
Immune system disorders
Leukopenia
|
3.4%
1/29
|
0.00%
0/27
|
|
General disorders
Laryngeal edema
|
3.4%
1/29
|
0.00%
0/27
|
|
General disorders
Rash
|
10.3%
3/29
|
7.4%
2/27
|
|
Gastrointestinal disorders
Nausea
|
6.9%
2/29
|
3.7%
1/27
|
|
Cardiac disorders
Arrhythmia
|
3.4%
1/29
|
0.00%
0/27
|
Additional Information
E. Sander Connolly Jr., MD
Columbia University Irving Medical Center
Phone: 212-305-0376
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place