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

NCT04148105 | Terminated Phase 4 DMC FDA Drug

• 1 other identifier: 1072359
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

Aneurysmal Subarachnoid Hemorrhage

Keywords

Delayed cerebral ischemia; Cerebral vasospasm; Cilostazol

Outcome Measures

Primary Outcomes (3)

• Delayed Cerebral Infarction

  Ischemic lesions demonstrated on follow-up CT or MRI will be interpreted as new cerebral infarctions

  Baseline

• Delayed Cerebral Infarction

  Ischemic lesions demonstrated on follow-up CT or MRI will be interpreted as new cerebral infarctions

  1 week (+/- 2 days) postoperatively

• 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 Outcomes (2)

• Symptomatic Cerebral Vasospasm

  At any point leading up to 14 days post-operation

• Radiographic Vasospasm

  Between 7-10 days postoperatively

Other Outcomes (2)

• Quality of Life Outcomes: Short-Form 12

  Baseline, 1 month postoperatively, 3 month postoperatively, and 6 month postoperatively

• Modified Rankin Scale

  Baseline, 1 month postoperatively, 3 month postoperatively, 6 month postoperatively

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Experimental

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.

Drug: Cilostazol 100 MG

Interventions

Cilostazol 100 MG 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

Experimental

Placebo OTHER

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

Placebo

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Henry Ford Health System: lead

Study Sites (1)

Ascension Providence Hospital

Southfield, Michigan, 48075, United States

Location

Related Publications (16)

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

  PMID: 25272066 BACKGROUND

• 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.

  PMID: 25187783 BACKGROUND

• 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.

  PMID: 6338383 BACKGROUND

• 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.

  PMID: 22556195 BACKGROUND

• 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.

  PMID: 8450326 BACKGROUND

• 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.

  PMID: 27160932 BACKGROUND

• 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.

  PMID: 23039152 BACKGROUND

• 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.

  PMID: 1545249 BACKGROUND

• 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.

  PMID: 15273542 BACKGROUND

• 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.

  PMID: 3964855 BACKGROUND

• 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.

  PMID: 4136544 BACKGROUND

• 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.

  PMID: 19359629 BACKGROUND

• 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.

  PMID: 22438522 BACKGROUND

• 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.

  PMID: 19550060 BACKGROUND

• 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

  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.

  PMID: 33020083 DERIVED

MeSH Terms

Conditions

Subarachnoid Hemorrhage; Vasospasm, Intracranial

Interventions

Cilostazol

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Boyd Richards, DO

  Div of Neurosurgery Ascension Providence Hospital MSU College of Human Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2019
• First Posted: November 1, 2019
• Study Start: November 1, 2019
• Primary Completion: May 21, 2023
• Study Completion: May 26, 2023
• Last Updated: May 31, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)