Subarachnoid Hemorrhage
Conditions
Keywords
limb preconditioning, remote preconditioning, ischemic preconditioning
Brief summary
In remote preconditioning, ischemia in one organ protects distant organs from ischemic insults. e.g. brief induced limb ischemia protects the brain from an otherwise more severe stroke. The objective of this study is to determine if remote ischemic preconditioning can be safely and effectively instituted in patients with subarachnoid hemorrhage, who are at high risk for developing disabling cerebral ischemia. The investigators will also preliminarily assess if there is evidence for neuroprotection. This will be a Phase 1b study. Additional objectives are: 1. to determine if remote ischemic preconditioning can be safely and effectively instituted in patients with subarachnoid hemorrhage, who are at high risk for developing disabling cerebral ischemia. 2. analogously to a dose-escalation study the investigators propose to study the safety and tolerability of increasing durations of limb ischemia until a target time of 10 minutes of limb ischemia has been reached.
Detailed description
The investigators propose to study patients with subarachnoid hemorrhage, who generally have a high risk of ischemic stroke in the 2 weeks following the initial bleed, and patients with clipped or coiled aneurysm. The investigators will apply a blood pressure cuff around leg and use it to interrupt the circulation for 5-10 minutes. The investigators will repeat this for a total of 3 times every 24 to 48 hours up to 14 days. The cuff will be inflated for 5-10 minutes and then deflated for 5 minutes. There will be 3 cycles of this. The cuff will be inflated to 200mmHg. The investigators will first start with 5 minutes of cuff inflation to either the arm or leg. The investigators will determine if this is safe in at least 6 patients. The investigators will then increase the duration of cuff inflation to 7.5 minutes for another 6 patients. If no adverse events are noted the investigators will the proceed to study 10 minutes of inflation in another 6 patients. If no side effects are noted the investigators will then determine that this is well tolerated. The study will be monitored by a Data Safety Monitoring Board who will make decisions about escalating the duration of cuff inflation. If 2 or more patients develop an adverse event that is related to the procedure the investigators will stop and no longer continue at that level of cuff inflation and the previous level of cuff inflation will be determined to be the safe and tolerated level. The investigators will collect safety data on adverse events such as tolerability, local tissue trauma or deep vein thrombosis.
Interventions
PROCEDUREremote limb preconditioning
3 cycles of up to 10 minutes leg ischemia
Sponsors
University of Miami
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
aneurismal subarachnoid hemorrhage
Exclusion criteria
1. Hunt Hess Scale \> 4 2. Inability to undergo limb preconditioning due to local wound or tissue breakdown, history of peripheral extremity vascular disease or patient discomfort. 3. Inability to obtain informed consent from the patient or a health care proxy. 4. Ankle-brachial index \< 0.7 5. Inability to start limb preconditioning within 4 days of bleeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Deep Vein Thrombosis for Safety Assessment. | 90 days | — |
| Visual Analog Scale Score as a Measure of Tolerability | 90 days | The visual analogue scale is a pain scale from 0-10, with 10 being maximum pain and is frequently used in research studies assessing patient discomfort. |
Participant flow
Recruitment details
Subjects admitted to a large community based teaching hospital were recruited between November 2008 and July 2010.
Participants by arm
| Arm | Count |
|---|---|
| Sham Preconditioning Subjects with subarachnoid hemorrhage will undergo escalating times of limb ischemia to determine tolerability and safety. The leg will be made transiently ischemic with application of a blood pressure cuff for up to 3 cycles of 10 minutes. | 7 |
| 5 Min Ischemia | 14 |
| 7.5 Min Ischemia | 7 |
| 10 Min Ischemia | 6 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| 7.5 Min Ischemia | Withdrawal by Subject | 0 | 0 | 1 | 0 |
| Sham Preconditioning | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Sham Preconditioning | 5 Min Ischemia | 7.5 Min Ischemia | 10 Min Ischemia | Total |
|---|---|---|---|---|---|
| Age, Continuous | 49 years STANDARD_DEVIATION 9 | 53 years STANDARD_DEVIATION 14 | 47 years STANDARD_DEVIATION 12 | 62 years STANDARD_DEVIATION 10 | 52 years STANDARD_DEVIATION 12 |
| Sex: Female, Male Female | 6 Participants | 9 Participants | 4 Participants | 3 Participants | 22 Participants |
| Sex: Female, Male Male | 1 Participants | 5 Participants | 3 Participants | 3 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 7 | 8 / 14 | 3 / 7 | 4 / 6 |
| serious Total, serious adverse events | 3 / 7 | 9 / 14 | 1 / 7 | 1 / 6 |
Outcome results
Primary
Number of Patients With Deep Vein Thrombosis for Safety Assessment.
Time frame: 90 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sham Preconditioning | Number of Patients With Deep Vein Thrombosis for Safety Assessment. | 0 participants |
| 5 Min Ischemia | Number of Patients With Deep Vein Thrombosis for Safety Assessment. | 3 participants |
| 7.5 Min Ischemia | Number of Patients With Deep Vein Thrombosis for Safety Assessment. | 0 participants |
| 10 Min Ischemia | Number of Patients With Deep Vein Thrombosis for Safety Assessment. | 0 participants |
Primary
Visual Analog Scale Score as a Measure of Tolerability
The visual analogue scale is a pain scale from 0-10, with 10 being maximum pain and is frequently used in research studies assessing patient discomfort.
Time frame: 90 days
Population: We escalated the ischemia times in cohorts of 6. Cohorts of 6 were prespecified at the beginning to the study. All analysis was intention to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sham Preconditioning | Visual Analog Scale Score as a Measure of Tolerability | 0 units on a scale | Standard Deviation 0 |
| 5 Min Ischemia | Visual Analog Scale Score as a Measure of Tolerability | 3.6 units on a scale | Standard Deviation 3.4 |
| 7.5 Min Ischemia | Visual Analog Scale Score as a Measure of Tolerability | 1.8 units on a scale | Standard Deviation 2.1 |
| 10 Min Ischemia | Visual Analog Scale Score as a Measure of Tolerability | 2.5 units on a scale | Standard Deviation 2.9 |