Timing Impact of Early vs. Late Cranioplasty on Hemicraniectomy Outcomes (TIMELY)

Comparing Outcomes Between Early and Standard-of-care Delayed Cranioplasty After Decompressive Hemicraniectomy

This prospective, randomized study aims to comprehensively evaluate the impact of cranioplasty timing on postoperative complications and long-term functional outcomes following decompressive hemicraniectomy (DHC). The primary endpoint focuses on comparing the rates of various postoperative complications, including infection, seizures, return to the operating room, and the need for ventriculoperitoneal shunting, between patients undergoing standard of care cranioplasty (>3 months after DHC) and those receiving early cranioplasty (within 8 weeks).

Study Overview

• Status: Recruiting
• Conditions: Stroke; Craniocerebral Trauma; Intracranial Hemorrhages
• Intervention / Treatment: Procedure: Early cranioplasty; Procedure: Standard-of-care cranioplasty

Detailed Description

This prospective, randomized study aims to comprehensively evaluate the impact of cranioplasty timing on postoperative complications and long-term functional outcomes following decompressive hemicraniectomy (DHC). The primary endpoint focuses on comparing the rates of various postoperative complications, including infection, seizures, return to the operating room, and the need for ventriculoperitoneal shunting, between patients undergoing standard of care cranioplasty (>3 months after DHC) and those receiving early cranioplasty (within 8 weeks).

The primary endpoint involves a comprehensive evaluation of long-term functional outcomes at 6 months post-injury ("injury" defined as "acute traumatic injury or source of increased intracranial pressure secondary to stroke or intracranial hemorrhage"). This assessment aims to determine whether the timing of cranioplasty influences patients' neurological recovery, cognitive function, and overall quality of life. By comparing the outcomes of patients who undergo standard of care cranioplasty with those who undergo early cranioplasty, the study seeks to provide valuable insights into the potential benefits of the latter approach.

The findings of this research hold the potential to guide clinical practice and inform decision-making for patients who have undergone DHC. By considering a range of complications and incorporating a robust statistical framework, the study contributes to a more nuanced understanding of the advantages and disadvantages associated with different cranioplasty timing strategies.

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pious Patel, MD; Phone Number: (215) 955-7000; Email: pious.patel@jefferson.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University Hospitals
      • Contact: Pious Patel, MD; Phone Number: (215) 955-7000

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adults of age greater than or equal to 18 years at the time of acute traumatic injury or source of increased intracranial pressure secondary to stroke or intracranial hemorrhage necessitating decompressive hemicraniectomy (DHC)
• Patient's cranial flap fulfills Craniectomy Contour Class A or B after 4 weeks postoperatively (doi:10.1227/ons.0000000000000689)
• Medically optimized for general anesthesia/surgery

Exclusion Criteria:

• Active systemic infection in weeks 6-8 post-DHC leading up to cranioplasty (e.g. pneumonia, urinary tract infection, soft tissue infection, bacteremia)
• Cranial infection in the post-DHC period
• Patient deemed not appropriate for early cranioplasty by attending neurosurgeon
• Patient mortality prior to 8 weeks post-injury ("injury" defined as "acute traumatic injury or source of increased intracranial pressure causing brain injury secondary to stroke or intracranial hemorrhage")

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Early cranioplasty; Cranioplasty procedure performed prior to 8 weeks following the initial decompressive hemicraniectomy.	Procedure: Early cranioplasty; Cranioplasty is the surgical procedure to restore the skull after a decompressive hemicraniectomy. The latter procedure is employed as a life-saving measure to relieve intracranial pressure in patients with acute cranial injuries. Early cranioplasty is defined as being performed within 8 weeks following the decompressive hemicraniectomy.
Placebo Comparator: Standard-of-care cranioplasty; Cranioplasty procedure performed after 3 months following the initial decompressive hemicraniectomy.	Procedure: Standard-of-care cranioplasty; Cranioplasty is the surgical procedure to restore the skull after a decompressive hemicraniectomy. The latter procedure is employed as a life-saving measure to relieve intracranial pressure in patients with acute cranial injuries. Standard-of-care cranioplasty is defined as being performed after 3 months following the decompressive hemicraniectomy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional outcome at 6 months post-decompressive hemicraniectomy	modified Rankin scale outcome at 6 months post-decompressive hemicraniectomy	6 months post-decompressive hemicraniectomy
Functional outcome at 12 months post-decompressive hemicraniectomy	modified Rankin scale outcome at 12 months post-decompressive hemicraniectomy	12 months post-decompressive hemicraniectomy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-cranioplasty seizure	Post-cranioplasty seizure occurrence, diagnosed clinically or on EEG	1 month post-cranioplasty
Post-cranioplasty hydrocephalus	Post-cranioplasty hydrocephalus or need for cerebrospinal fluid diversion	1 month post-cranioplasty
Post-cranioplasty return to operating room	All-cause return to operating room after cranioplasty	1 month post-cranioplasty
Post-cranioplasty infection	Surgical site or intracranial infection after cranioplasty	12 months post-cranioplasty
Post-cranioplasty disposition	Post-cranioplasty disposition (home, acute rehab, subacute rehab, death)	12 months post-cranioplasty
Post-cranioplasty length of hospital stay	Post-cranioplasty length of hospital stay	12 months post-cranioplasty
Readmission within 30 days post-cranioplasty	Readmission within 30 days post-cranioplasty	30 days post-cranioplasty

Collaborators and Investigators

• Sponsor: Thomas Jefferson University

Publications and helpful links

General Publications

• Patel PD, Khanna O, Gooch MR, Glener SR, Mouchtouris N, Momin AA, Sioutas G, Amllay A, Barsouk A, El Naamani K, Yudkoff C, Wyler DA, Jallo JI, Tjoumakaris S, Jabbour PM, Harrop JS. Clinical Outcomes After Ultra-Early Cranioplasty Using Craniectomy Contour Classification as a Patient Selection Criterion. Oper Neurosurg (Hagerstown). 2023 Jul 1;25(1):72-80. doi: 10.1227/ons.0000000000000689. Epub 2023 May 5.
• Malcolm JG, Rindler RS, Chu JK, Chokshi F, Grossberg JA, Pradilla G, Ahmad FU. Early Cranioplasty is Associated with Greater Neurological Improvement: A Systematic Review and Meta-Analysis. Neurosurgery. 2018 Mar 1;82(3):278-288. doi: 10.1093/neuros/nyx182.
• Eaton JC, Greil ME, Nistal D, Caldwell DJ, Robinson E, Aljuboori Z, Temkin N, Bonow RH, Chesnut RM. Complications associated with early cranioplasty for patients with traumatic brain injury: a 25-year single-center analysis. J Neurosurg. 2022 Jan 21;137(3):776-781. doi: 10.3171/2021.11.JNS211557. Print 2022 Sep 1.
• Sethi A, Chee K, Kaakani A, Beauchamp K, Kang J. Ultra-Early Cranioplasty versus Conventional Cranioplasty: A Retrospective Cohort Study at an Academic Level 1 Trauma Center. Neurotrauma Rep. 2022 Aug 1;3(1):286-291. doi: 10.1089/neur.2022.0026. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: September 26, 2024
• First Submitted That Met QC Criteria: October 8, 2024
• First Posted (Actual): October 9, 2024

Study Record Updates

• Last Update Posted (Actual): July 23, 2025
• Last Update Submitted That Met QC Criteria: July 21, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: stroke; intracerebral hemorrhage; neurosurgery; intracranial hemorrhage; cranioplasty; Decompressive hemicraniectomy; cranial trauma
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Wounds and Injuries; Pathologic Processes; Trauma, Nervous System; Hemorrhage; Intracranial Hemorrhages; Craniocerebral Trauma
• Other Study ID Numbers: iRISID-2024-3103

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No