Cilostazol and Nimodipine Combined Therapy After Aneurysmal Subarachnoid Hemorrhage (aSAH)

Aneurysmal Subarachnoid Hemorrhage Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04148105
• Other study ID #: 1072359
• Status: Recruiting
• Phase: Phase 4
• Start date: November 1, 2019
• Est. completion date: July 1, 2024

Study information

• Verified date: April 2023
• Source: Ascension South East Michigan
• Contact: Doris Tong, MD
• Phone: (248) 663-1826
• Email: doris.tong[@]michiganspineandbrainsurgery.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: July 1, 2024
• Est. primary completion date: January 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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)

Related Conditions & MeSH terms

• Aneurysmal Subarachnoid Hemorrhage
• Hemorrhage
• Subarachnoid Hemorrhage

Intervention

Drug:
• Cilostazol 100 MG
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

Other:
• Placebo
The standard treatment regimen of 60 mg nimodipine every 4 hours for 21 days and the standard aneurysmal subarachnoid treatment pathway

Locations

Country	Name	City	State
United States	Ascension Providence Hospital	Southfield	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Ascension South East Michigan

Country where clinical trial is conducted

United States, 

References & Publications (15)

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

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. — View 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. — View Citation

D'Souza S. Aneurysmal Subarachnoid Hemorrhage. J Neurosurg Anesthesiol. 2015 Jul;27(3):222-40. doi: 10.1097/ANA.0000000000000130. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Quality of Life Outcomes: Short-Form 12	Short-Form 12 is answered by the patient. On a scale of 0-100, a higher score means better overall physical and mental health.	Baseline, 1 month postoperatively, 3 month postoperatively, and 6 month postoperatively
Other	Modified Rankin Scale	The patient's clinical status is graded on a scale of 0-6. An increasing score means a worse functional outcome.	Baseline, 1 month postoperatively, 3 month postoperatively, 6 month postoperatively
Primary	Delayed Cerebral Infarction	Ischemic lesions demonstrated on follow-up CT or MRI will be interpreted as new cerebral infarctions	Baseline
Primary	Delayed Cerebral Infarction	Ischemic lesions demonstrated on follow-up CT or MRI will be interpreted as new cerebral infarctions	1 week (+/- 2 days) postoperatively
Primary	Delayed Cerebral Infarction	Ischemic lesions demonstrated on follow-up CT or MRI will be interpreted as new cerebral infarctions	1 month (+/- 7 days) postoperatively
Secondary	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	At any point leading up to 14 days post-operation
Secondary	Radiographic Vasospasm	Arterial narrowing not attributable to atherosclerosis, catheter-induced vasospasm, or vessel hypoplasia	Between 7-10 days postoperatively