Back to resultsCilostazol and Nimodipine Combined Therapy After Aneurysmal Subarachnoid Hemorrhage (aSAH)
Primary Purpose
Aneurysmal Subarachnoid Hemorrhage
Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Cilostazol 100 MG
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Aneurysmal Subarachnoid Hemorrhage focused on measuring Delayed cerebral ischemia, Cerebral vasospasm, Cilostazol
Eligibility Criteria
Inclusion Criteria:
- 18 years of age or older
- Anterior circulation aneurysm
- Patients who have undergone surgical intervention
- Absence of rebleeding or new intracranial hemorrhage noted on post-intervention CT scan
- Consent for study participation
Exclusion Criteria:
- Non-aneurysmal subarachnoid hemorrhage
- Multiple ruptured aneurysms
- Patients with congestive heart failure
- Severe aneurysmal subarachnoid hemorrhage (Hunt Hess Grade V)
- Active pathological bleeding
- Allergy to cilostazol
- Positive pregnancy test
- Coagulopathy not caused by anti-coagulant use
- History of hemorrhagic complications (gastrointestinal bleeding, etc)
- Uncontrolled or severe comorbidity that would qualify as an absolute contraindication for cilostazol
- Patients requiring anticoagulant/antiplatelet treatment following intervention (e.g. stent-assisted coiling or flow-diverting stent obliteration of aneurysm)
Sites / Locations
- Ascension Providence HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
Experimental
Arm Description
Implement standard treatment regimen of 60 mg nimodipine every 4 hours for 21 days and the standard aneurysmal subarachnoid treatment pathway.
Administer 100 mg cilostazol, twice daily for 14 days. In addition, implement the standard treatment regimen of 60 mg nimodipine every 4 hours for 21 days, and the standard aneurysmal subarachnoid treatment pathway.
Outcomes
Primary Outcome Measures
Delayed Cerebral Infarction
Ischemic lesions demonstrated on follow-up CT or MRI will be interpreted as new cerebral infarctions
Delayed Cerebral Infarction
Ischemic lesions demonstrated on follow-up CT or MRI will be interpreted as new cerebral infarctions
Delayed Cerebral Infarction
Ischemic lesions demonstrated on follow-up CT or MRI will be interpreted as new cerebral infarctions
Secondary Outcome Measures
Symptomatic Cerebral Vasospasm
Development of a new focal or global neurological deficit or deterioration of at least 2 points on the Glasgow Coma Scale which was not explained by initial hemorrhage, re-bleeding, hydrocephalus, surgical complications, fever, infections, or electrolyte or metabolic disturbances; regardless of cerebral infarctions or angiographic vasospasm on imaging
Radiographic Vasospasm
Arterial narrowing not attributable to atherosclerosis, catheter-induced vasospasm, or vessel hypoplasia
Full Information
NCT ID
NCT04148105
First Posted
October 21, 2019
Last Updated
April 18, 2023
Sponsor
Ascension South East Michigan
1. Study Identification
Unique Protocol Identification Number
NCT04148105
Brief Title
Cilostazol and Nimodipine Combined Therapy After Aneurysmal Subarachnoid Hemorrhage (aSAH)
Official Title
Efficacy and Safety of Cilostazol-Nimodipine Combined Therapy on Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage (aSAH): A Prospective, Randomized, Double-Blinded, Placebo-Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 1, 2019 (Actual)
Primary Completion Date
January 1, 2024 (Anticipated)
Study Completion Date
July 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ascension South East Michigan
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The investigators seek to demonstrate that the combined use of cilostazol and nimodipine will significantly decrease the rate of delayed cerebral infarction and cerebral vasospasm after cerebrovascular intervention when compared to nimodipine alone.
Detailed Description
This research study is for people who have a brain hemorrhage, due to a ruptured aneurysm. Adding the drug cilostazol to the standard care may improve outcomes after surgery. The blood within the brain following aneurysmal hemorrhage can have harmful effects on the blood vessels causing them to narrow and thus decrease blood flow; this process is called vasospasm. Decreased blood flow in the brain can lead to more damage. Delayed cerebral ischemia is a complication which is believed to be a consequence of reduced blood flow to the brain following this type of hemorrhage. Cilostazol opens blood vessels and reduces the formation of blood clots. The standard treatment of these hemorrhages currently involves the use of nimodipine which also relaxes blood vessels and allows blood to flow more freely. The combination of these two drugs cilostazol and nimodipine may improve neurologic outcomes after surgery.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aneurysmal Subarachnoid Hemorrhage
Keywords
Delayed cerebral ischemia, Cerebral vasospasm, Cilostazol
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Implement standard treatment regimen of 60 mg nimodipine every 4 hours for 21 days and the standard aneurysmal subarachnoid treatment pathway.
Arm Title
Experimental
Arm Type
Experimental
Arm Description
Administer 100 mg cilostazol, twice daily for 14 days. In addition, implement the standard treatment regimen of 60 mg nimodipine every 4 hours for 21 days, and the standard aneurysmal subarachnoid treatment pathway.
Intervention Type
Drug
Intervention Name(s)
Cilostazol 100 MG
Intervention Description
The addition of 100 mg cilostazol, twice daily for 14 days, to the standard treatment regimen of 60 mg nimodipine every 4 hours for 21 days and the standard aneurysmal subarachnoid treatment pathway
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
The standard treatment regimen of 60 mg nimodipine every 4 hours for 21 days and the standard aneurysmal subarachnoid treatment pathway
Primary Outcome Measure Information:
Title
Delayed Cerebral Infarction
Description
Ischemic lesions demonstrated on follow-up CT or MRI will be interpreted as new cerebral infarctions
Time Frame
Baseline
Title
Delayed Cerebral Infarction
Description
Ischemic lesions demonstrated on follow-up CT or MRI will be interpreted as new cerebral infarctions
Time Frame
1 week (+/- 2 days) postoperatively
Title
Delayed Cerebral Infarction
Description
Ischemic lesions demonstrated on follow-up CT or MRI will be interpreted as new cerebral infarctions
Time Frame
1 month (+/- 7 days) postoperatively
Secondary Outcome Measure Information:
Title
Symptomatic Cerebral Vasospasm
Description
Development of a new focal or global neurological deficit or deterioration of at least 2 points on the Glasgow Coma Scale which was not explained by initial hemorrhage, re-bleeding, hydrocephalus, surgical complications, fever, infections, or electrolyte or metabolic disturbances; regardless of cerebral infarctions or angiographic vasospasm on imaging
Time Frame
At any point leading up to 14 days post-operation
Title
Radiographic Vasospasm
Description
Arterial narrowing not attributable to atherosclerosis, catheter-induced vasospasm, or vessel hypoplasia
Time Frame
Between 7-10 days postoperatively
Other Pre-specified Outcome Measures:
Title
Quality of Life Outcomes: Short-Form 12
Description
Short-Form 12 is answered by the patient. On a scale of 0-100, a higher score means better overall physical and mental health.
Time Frame
Baseline, 1 month postoperatively, 3 month postoperatively, and 6 month postoperatively
Title
Modified Rankin Scale
Description
The patient's clinical status is graded on a scale of 0-6. An increasing score means a worse functional outcome.
Time Frame
Baseline, 1 month postoperatively, 3 month postoperatively, 6 month postoperatively
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
18 years of age or older
Anterior circulation aneurysm
Patients who have undergone surgical intervention
Absence of rebleeding or new intracranial hemorrhage noted on post-intervention CT scan
Consent for study participation
Exclusion Criteria:
Non-aneurysmal subarachnoid hemorrhage
Multiple ruptured aneurysms
Patients with congestive heart failure
Severe aneurysmal subarachnoid hemorrhage (Hunt Hess Grade V)
Active pathological bleeding
Allergy to cilostazol
Positive pregnancy test
Coagulopathy not caused by anti-coagulant use
History of hemorrhagic complications (gastrointestinal bleeding, etc)
Uncontrolled or severe comorbidity that would qualify as an absolute contraindication for cilostazol
Patients requiring anticoagulant/antiplatelet treatment following intervention (e.g. stent-assisted coiling or flow-diverting stent obliteration of aneurysm)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Doris Tong, MD
Phone
(248) 663-1826
Email
doris.tong@michiganspineandbrainsurgery.com
First Name & Middle Initial & Last Name or Official Title & Degree
Ascher Kaufmann, MD
Phone
(713) 392-7118
Email
ascher07@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boyd Richards, DO
Organizational Affiliation
Div of Neurosurgery Ascension Providence Hospital MSU College of Human Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ascension Providence Hospital
City
Southfield
State/Province
Michigan
ZIP/Postal Code
48075
Country
United States
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
All of the individual participant data collected during the trial, after deidentification will be made available following publication upon request at the discretion of the principal investigator.
Citations:
PubMed Identifier
25272066
Citation
D'Souza S. Aneurysmal Subarachnoid Hemorrhage. J Neurosurg Anesthesiol. 2015 Jul;27(3):222-40. doi: 10.1097/ANA.0000000000000130.
Results Reference
background
PubMed Identifier
25187783
Citation
Dabus G, Nogueira RG. Current options for the management of aneurysmal subarachnoid hemorrhage-induced cerebral vasospasm: a comprehensive review of the literature. Interv Neurol. 2013 Oct;2(1):30-51. doi: 10.1159/000354755.
Results Reference
background
PubMed Identifier
6338383
Citation
Allen GS, Ahn HS, Preziosi TJ, Battye R, Boone SC, Boone SC, Chou SN, Kelly DL, Weir BK, Crabbe RA, Lavik PJ, Rosenbloom SB, Dorsey FC, Ingram CR, Mellits DE, Bertsch LA, Boisvert DP, Hundley MB, Johnson RK, Strom JA, Transou CR. Cerebral arterial spasm--a controlled trial of nimodipine in patients with subarachnoid hemorrhage. N Engl J Med. 1983 Mar 17;308(11):619-24. doi: 10.1056/NEJM198303173081103.
Results Reference
background
PubMed Identifier
22556195
Citation
Connolly ES Jr, Rabinstein AA, Carhuapoma JR, Derdeyn CP, Dion J, Higashida RT, Hoh BL, Kirkness CJ, Naidech AM, Ogilvy CS, Patel AB, Thompson BG, Vespa P; American Heart Association Stroke Council; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; Council on Cardiovascular Surgery and Anesthesia; Council on Clinical Cardiology. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/american Stroke Association. Stroke. 2012 Jun;43(6):1711-37. doi: 10.1161/STR.0b013e3182587839. Epub 2012 May 3.
Results Reference
background
PubMed Identifier
8450326
Citation
Haley EC Jr, Kassell NF, Torner JC. A randomized controlled trial of high-dose intravenous nicardipine in aneurysmal subarachnoid hemorrhage. A report of the Cooperative Aneurysm Study. J Neurosurg. 1993 Apr;78(4):537-47. doi: 10.3171/jns.1993.78.4.0537.
Results Reference
background
PubMed Identifier
27160932
Citation
Veldeman M, Hollig A, Clusmann H, Stevanovic A, Rossaint R, Coburn M. Delayed cerebral ischaemia prevention and treatment after aneurysmal subarachnoid haemorrhage: a systematic review. Br J Anaesth. 2016 Jul;117(1):17-40. doi: 10.1093/bja/aew095. Epub 2016 May 8.
Results Reference
background
PubMed Identifier
23039152
Citation
Senbokuya N, Kinouchi H, Kanemaru K, Ohashi Y, Fukamachi A, Yagi S, Shimizu T, Furuya K, Uchida M, Takeuchi N, Nakano S, Koizumi H, Kobayashi C, Fukasawa I, Takahashi T, Kuroda K, Nishiyama Y, Yoshioka H, Horikoshi T. Effects of cilostazol on cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a multicenter prospective, randomized, open-label blinded end point trial. J Neurosurg. 2013 Jan;118(1):121-30. doi: 10.3171/2012.9.JNS12492. Epub 2012 Oct 5.
Results Reference
background
PubMed Identifier
1545249
Citation
Shibuya M, Suzuki Y, Sugita K, Saito I, Sasaki T, Takakura K, Nagata I, Kikuchi H, Takemae T, Hidaka H, et al. Effect of AT877 on cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Results of a prospective placebo-controlled double-blind trial. J Neurosurg. 1992 Apr;76(4):571-7. doi: 10.3171/jns.1992.76.4.0571.
Results Reference
background
PubMed Identifier
15273542
Citation
Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. doi: 10.1097/01.sla.0000133083.54934.ae.
Results Reference
background
PubMed Identifier
3964855
Citation
Voldby B, Enevoldsen EM, Jensen FT. Regional CBF, intraventricular pressure, and cerebral metabolism in patients with ruptured intracranial aneurysms. J Neurosurg. 1985 Jan;62(1):48-58. doi: 10.3171/jns.1985.62.1.0048.
Results Reference
background
PubMed Identifier
4136544
Citation
Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet. 1974 Jul 13;2(7872):81-4. doi: 10.1016/s0140-6736(74)91639-0. No abstract available.
Results Reference
background
PubMed Identifier
19359629
Citation
Frontera JA, Fernandez A, Schmidt JM, Claassen J, Wartenberg KE, Badjatia N, Connolly ES, Mayer SA. Defining vasospasm after subarachnoid hemorrhage: what is the most clinically relevant definition? Stroke. 2009 Jun;40(6):1963-8. doi: 10.1161/STROKEAHA.108.544700. Epub 2009 Apr 9.
Results Reference
background
PubMed Identifier
22438522
Citation
Zannad F, Gattis Stough W, McMurray JJ, Remme WJ, Pitt B, Borer JS, Geller NL, Pocock SJ. When to stop a clinical trial early for benefit: lessons learned and future approaches. Circ Heart Fail. 2012 Mar 1;5(2):294-302. doi: 10.1161/CIRCHEARTFAILURE.111.965707. No abstract available.
Results Reference
background
PubMed Identifier
19550060
Citation
Puri KS, Suresh KR, Gogtay NJ, Thatte UM. Declaration of Helsinki, 2008: implications for stakeholders in research. J Postgrad Med. 2009 Apr-Jun;55(2):131-4. doi: 10.4103/0022-3859.52846.
Results Reference
background
Citation
Abraham J. International Conference On Harmonisation Of Technical Requirements For Registration Of Pharmaceuticals For Human Use. In: Brouder A, Tietje C, eds. Handbook of Transnational Economic Governance Regimes. Brill 2009. 1041-54. doi:10.1163/ej.9789004163300.i-1081.897
Results Reference
background
PubMed Identifier
33020083
Citation
Dawley T, Claus CF, Tong D, Rajamand S, Sigler D, Bahoura M, Garmo L, Soo TM, Kelkar P, Richards B. Efficacy and safety of cilostazol-nimodipine combined therapy on delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage: a prospective, randomised, double-blinded, placebo-controlled trial protocol. BMJ Open. 2020 Oct 5;10(10):e036217. doi: 10.1136/bmjopen-2019-036217.
Results Reference
derived
Learn more about this trial
Cilostazol and Nimodipine Combined Therapy After Aneurysmal Subarachnoid Hemorrhage (aSAH)
We'll reach out to this number within 24 hrs