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

NCT ID: NCT04148105

Last Updated: 2024-05-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE4

Total Enrollment

19 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-11-01

Study Completion Date

2023-05-26

Brief Summary

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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

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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.

Conditions

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Aneurysmal Subarachnoid Hemorrhage

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

Implement standard treatment regimen of 60 mg nimodipine every 4 hours for 21 days and the standard aneurysmal subarachnoid treatment pathway.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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

Experimental

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.

Group Type EXPERIMENTAL

Cilostazol 100 MG

Intervention Type DRUG

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

Interventions

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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

Intervention Type DRUG

Placebo

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

Intervention Type OTHER

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Henry Ford Health System

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Boyd Richards, DO

Role: PRINCIPAL_INVESTIGATOR

Div of Neurosurgery Ascension Providence Hospital MSU College of Human Medicine

Locations

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Ascension Providence Hospital

Southfield, Michigan, United States

Site Status

Countries

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United States

References

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

Reference Type BACKGROUND
PMID: 25272066 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25187783 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 6338383 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22556195 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8450326 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27160932 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23039152 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1545249 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15273542 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3964855 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 4136544 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19359629 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22438522 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19550060 (View on PubMed)

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

Reference Type BACKGROUND

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.

Reference Type DERIVED
PMID: 33020083 (View on PubMed)

Other Identifiers

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1072359

Identifier Type: -

Identifier Source: org_study_id

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