Regional Versus General Anesthesia for Promoting Independence After Hip Fracture (REGAIN)

A Randomized Controlled Trial of Regional Versus General Anesthesia for Promoting Independence After Hip Fracture

The purpose of this study is to find out if two types of standard care anesthesia are the same or if one is better for people who have hip fractures.

Study Overview

• Status: Active, not recruiting
• Conditions: Hip Fractures
• Intervention / Treatment: Procedure: Regional Anesthesia; Procedure: General Anesthesia

Detailed Description

Hip fracture is a clinical condition that involves a break in the femur (hip bone) near where it attaches to the pelvis. Hip fractures occur more than 300,000 times each year in the US and over 1.6 million times each year worldwide.

Over 90% of hip fractures occur in individuals aged 50 or older, most commonly resulting from low-energy traumatic injuries, such as falls from standing in the context of established osteoporosis, chronic illness, or disability. Surgical treatment, via fixation of the fractured bone or partial or total replacement of the hip joint, is indicated for all types of hip fractures and approximately 95% of hip fracture patients undergo surgery.

No evidence-based interventions now exist to improve functional outcomes after hip fracture surgery beyond the immediate postoperative period. Nearly all hip fracture patients require orthopedic surgery and anesthesia, making the anesthetic care episode a major opportunity to impact outcomes.

Spinal and general anesthesia represent the two standard care approaches to anesthesia for hip fracture surgery. Basic and clinical research has identified multiple plausible mechanisms by which spinal anesthesia may improve outcomes after hip fracture; nonetheless, major guidelines and systematic reviews have identified key evidence gaps and anesthesia care for hip fracture varies markedly in practice. While spinal and general anesthesia for hip fracture have been previously compared in retrospective studies and small randomized trials, much of the available prospective trial data is old and may not be reflective of current clinical practice.

REGAIN will be the first pragmatic multicenter prospective randomized trial of spinal versus general anesthesia for hip fracture surgery designed to evaluate the association of anesthesia technique with functional recovery after hip fracture. As such, it will fill critical evidence gaps to inform policy and practice.

Approximately 2,424 subjects will be enrolled (i.e. informed consent for participation will be obtained) in order to yield approximately 1,600 randomized patients. This estimate is based on an assumption that one in three patients (33%) who undergo consent prior to surgery will not be randomized on the day of surgery due to active clinical issues, timing of medication dosing, clinical assessments by treating physicians or the site Clinical Director or their designate, or patient withdrawal of consent.

• Study Type: Interventional
• Enrollment (Actual): 1848
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta
  • British Columbia
    • New Westminster, British Columbia, Canada, V3L 3M2
      • Simon Fraser Orthopaedic Fund - Royal Columbian Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Dalhousie University
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1Y 4E9
      • Ottawa Hospital
    • Toronto, Ontario, Canada
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada
      • Toronto Western Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University of Alabama Birmingham
  • California
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
    • New Haven, Connecticut, United States, 06520
      • Yale School of Medicine
  • Delaware
    • Newark, Delaware, United States, 19718
      • Christiana Care Health Services
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida Gainesville
    • Jacksonville, Florida, United States, 32209
      • University of Florida Jacksonville
    • Winter Park, Florida, United States, 32792
      • Florida Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospital & Clinics
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Bayview Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital & Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper University Hospital
    • Englewood, New Jersey, United States, 07631
      • Englewood Hospital and Medical Center
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers-Robert Wood Johnson University Hospital
  • New York
    • Brooklyn, New York, United States, 11219
      • Maimonides Medical Center
    • Mineola, New York, United States, 11501
      • NYU-Winthrop Hospital
    • New York, New York, United States, 10003
      • NYU Langone Medical Center
    • New York, New York, United States, 10065
      • New York-Presbyterian Hospital/Weill Cornell Medical Center
    • Stony Brook, New York, United States, 11794
      • Stony Brook University
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Baptist Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oregon
    • Springfield, Oregon, United States, 97477
      • Sacred Heart at RiverBend
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Presbyterian Medical Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospitals
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Health Network
    • Reading, Pennsylvania, United States, 19611
      • Reading Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center
  • Texas
    • Austin, Texas, United States, 78705
      • University Medical Center Brackenridge and Seton Medical Center Williamson
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center
  • Virginia
    • Fairfax, Virginia, United States, 22042
      • Inova Fairfax Medical Campus
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University Medical Center
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin-Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinically or radiographically diagnosed intracapsular or extracapsular hip fracture
• Planned surgical treatment via hemiarthroplasty, total hip arthroplasty or appropriate fixation procedure
• Ability to walk 10 feet or across a room without human assistance before fracture

Exclusion Criteria:

• Planned concurrent surgery not amenable to spinal anesthesia
• Absolute contraindications to spinal anesthesia
• Periprosthetic fracture

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Regional Anesthesia; Approximately half of the subjects will be randomized to the arm which receives Regional Anesthesia.	Procedure: Regional Anesthesia; Regional anesthesia involves temporarily numbing parts of the body with nerve blocks. Spinal anesthesia is a type of regional anesthesia that uses medications injected into the fluid surrounding the spinal cord to temporarily numb the legs and lower abdomen. Spinal anesthesia is the most widely used type of regional anesthesia for hip fracture surgery. While intravenous sedation is typically used for comfort with spinal anesthesia, invasive airway interventions are not typically required.; Other Names: Regional Block or Spinal Block
Active Comparator: General Anesthesia; Approximately half of the subjects will be randomized to the arm which receives General Anesthesia.	Procedure: General Anesthesia; General anesthesia uses injected or inhaled medications to keep people unconscious during surgery. Since general anesthesia depresses breathing and impairs protective airway reflexes, invasive airway interventions such as breathing tube placement and mechanical ventilation are usually required.; Other Names: General Endotracheal Anesthesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death or inability to walk 10 feet or across a room without human assistance	Will be assessed via telephone interview	Approximately 60 days after Randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall health and disability	Will be assessed via the World Health Organization Disability Assessment Schedule (WHODAS)	Approximately 60, 180, and 365 days after randomization
Ability to return to home	Will be assessed via telephone interview	Approximately 60, 180, and 365 days after randomization
Chronic Pain	Will be assessed via the Numeric Rating Scale (NRS) and the need for prescription medications as evaluated during telephone interview	Approximately 60, 180, and 365 days after randomization
Cognitive Function	Will be assessed via Short Blessed Test	Baseline and approximately 60, 180, and 365 days after randomization
All-cause mortality	Will be assessed via telephone interview and National Death Index (NDI) search	Approximately 60, 180, and 365 days after randomization
Cause of death	Will be assessed via NDI search	One year after randomization
Need for assistive devices for walking	Will be assessed via telephone interview	Approximately 60, 180, and 365 days after randomization
Acute postoperative pain	Will be assessed via in-person interview	Before surgery and daily through postoperative day 3 or day of discharge, whichever occurs first
Satisfaction with care	Will be assessed via Bauer Patient Satisfaction Questionnaire	Postoperative day 3 or day of discharge, whichever occurs first
Postoperative delirium	Will be assessed via 3-minute Diagnostic Interview for Confusion Assessment Method (3D-CAM) assessment tool	Baseline and daily through postoperative day 3 or day of discharge, whichever occurs first
Inpatient mortality and major inpatient morbidity	Will be assessed via medical chart review	During initial hospitalization until day of discharge or 30 days after randomization, whichever occurs first

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: Patient-Centered Outcomes Research Institute
• Investigators: Principal Investigator: Mark D Neuman, MD, MSc, University of Pennsylvania

Publications and helpful links

General Publications

• Neuman MD, Feng R, Ellenberg SS, Sieber F, Sessler DI, Magaziner J, Elkassabany N, Schwenk ES, Dillane D, Marcantonio ER, Menio D, Ayad S, Hassan M, Stone T, Papp S, Donegan D, Marshall M, Jaffe JD, Luke C, Sharma B, Azim S, Hymes R, Chin KJ, Sheppard R, Perlman B, Sappenfield J, Hauck E, Hoeft MA, Tierney A, Gaskins LJ, Horan AD, Brown T, Dattilo J, Carson JL; REGAIN (Regional versus General Anesthesia for Promoting Independence after Hip Fracture) Investigators*, Looke T, Bent S, Franco-Mora A, Hedrick P, Newbern M, Tadros R, Pealer K, Vlassakov K, Buckley C, Gavin L, Gorbatov S, Gosnell J, Steen T, Vafai A, Zeballos J, Hruslinski J, Cardenas L, Berry A, Getchell J, Quercetti N, Bajracharya G, Billow D, Bloomfield M, Cuko E, Elyaderani MK, Hampton R, Honar H, Khoshknabi D, Kim D, Krahe D, Lew MM, Maheshwer CB, Niazi A, Saha P, Salih A, de Swart RJ, Volio A, Bolkus K, DeAngelis M, Dodson G, Gerritsen J, McEniry B, Mitrev L, Kwofie MK, Belliveau A, Bonazza F, Lloyd V, Panek I, Dabiri J, Chavez C, Craig J, Davidson T, Dietrichs C, Fleetwood C, Foley M, Getto C, Hailes S, Hermes S, Hooper A, Koener G, Kohls K, Law L, Lipp A, Losey A, Nelson W, Nieto M, Rogers P, Rutman S, Scales G, Sebastian B, Stanciu T, Lobel G, Giampiccolo M, Herman D, Kaufman M, Murphy B, Pau C, Puzio T, Veselsky M, Apostle K, Boyer D, Fan BC, Lee S, Lemke M, Merchant R, Moola F, Payne K, Perey B, Viskontas D, Poler M, D'Antonio P, O'Neill G, Abdullah A, Fish-Fuhrmann J, Giska M, Fidkowski C, Guthrie ST, Hakeos W, Hayes L, Hoegler J, Nowak K, Beck J, Cuff J, Gaski G, Haaser S, Holzman M, Malekzadeh AS, Ramsey L, Schulman J, Schwartzbach C, Azefor T, Davani A, Jaberi M, Masear C, Haider SB, Chungu C, Ebrahimi A, Fikry K, Marcantonio A, Shelvan A, Sanders D, Clarke C, Lawendy A, Schwartz G, Garg M, Kim J, Caruci J, Commeh E, Cuevas R, Cuff G, Franco L, Furgiuele D, Giuca M, Allman M, Barzideh O, Cossaro J, D'Arduini A, Farhi A, Gould J, Kafel J, Patel A, Peller A, Reshef H, Safur M, Toscano F, Tedore T, Akerman M, Brumberger E, Clark S, Friedlander R, Jegarl A, Lane J, Lyden JP, Mehta N, Murrell MT, Painter N, Ricci W, Sbrollini K, Sharma R, Steel PAD, Steinkamp M, Weinberg R, Wellman DS, Nader A, Fitzgerald P, Ritz M, Bryson G, Craig A, Farhat C, Gammon B, Gofton W, Harris N, Lalonde K, Liew A, Meulenkamp B, Sonnenburg K, Wai E, Wilkin G, Troxell K, Alderfer ME, Brannen J, Cupitt C, Gerhart S, McLin R, Sheidy J, Yurick K, Chen F, Dragert K, Kiss G, Malveaux H, McCloskey D, Mellender S, Mungekar SS, Noveck H, Sagebien C, Biby L, McKelvy G, Richards A, Abola R, Ayala B, Halper D, Mavarez A, Rizwan S, Choi S, Awad I, Flynn B, Henry P, Jenkinson R, Kaustov L, Lappin E, McHardy P, Singh A, Donnelly J, Gonzalez M, Haydel C, Livelsberger J, Pazionis T, Slattery B, Vazquez-Trejo M, Baratta J, Cirullo M, Deiling B, Deschamps L, Glick M, Katz D, Krieg J, Lessin J, Mojica J, Torjman M, Jin R, Salpeter MJ, Powell M, Simmons J, Lawson P, Kukreja P, Graves S, Sturdivant A, Bryant A, Crump SJ, Verrier M, Green J, Menon M, Applegate R, Arias A, Pineiro N, Uppington J, Wolinsky P, Gunnett A, Hagen J, Harris S, Hollen K, Holloway B, Horodyski MB, Pogue T, Ramani R, Smith C, Woods A, Warrick M, Flynn K, Mongan P, Ranganath Y, Fernholz S, Ingersoll-Weng E, Marian A, Seering M, Sibenaller Z, Stout L, Wagner A, Walter A, Wong C, Orwig D, Goud M, Helker C, Mezenghie L, Montgomery B, Preston P, Schwartz JS, Weber R, Fleisher LA, Mehta S, Stephens-Shields AJ, Dinh C, Chelly JE, Goel S, Goncz W, Kawabe T, Khetarpal S, Monroe A, Shick V, Breidenstein M, Dominick T, Friend A, Mathews D, Lennertz R, Sanders R, Akere H, Balweg T, Bo A, Doro C, Goodspeed D, Lang G, Parker M, Rettammel A, Roth M, White M, Whiting P, Allen BFS, Baker T, Craven D, McEvoy M, Turnbo T, Kates S, Morgan M, Willoughby T, Weigel W, Auyong D, Fox E, Welsh T, Cusson B, Dobson S, Edwards C, Harris L, Henshaw D, Johnson K, McKinney G, Miller S, Reynolds J, Segal BS, Turner J, VanEenenaam D, Weller R, Lei J, Treggiari M, Akhtar S, Blessing M, Johnson C, Kampp M, Kunze K, O'Connor M, Looke T, Tadros R, Vlassakov K, Cardenas L, Bolkus K, Mitrev L, Kwofie MK, Dabiri J, Lobel G, Poler M, Giska M, Sanders D, Schwartz G, Giuca M, Tedore T, Nader A, Bryson G, Troxell K, Kiss G, Choi S, Powell M, Applegate R, Warrick M, Ranganath Y, Chelly JE, Lennertz R, Sanders R, Allen BFS, Kates S, Weigel W, Li J, Wijeysundera DN, Kheterpal S, Moore RH, Smith AK, Tosi LL, Looke T, Mehta S, Fleisher L, Hruslinski J, Ramsey L, Langlois C, Mezenghie L, Montgomery B, Oduwole S, Rose T; REGAIN (Regional versus General Anesthesia for Promoting Independence after Hip Fracture) Investigators. Pain, Analgesic Use, and Patient Satisfaction With Spinal Versus General Anesthesia for Hip Fracture Surgery : A Randomized Clinical Trial. Ann Intern Med. 2022 Jul;175(7):952-960. doi: 10.7326/M22-0320. Epub 2022 Jun 14.
• Neuman MD, Feng R, Carson JL, Gaskins LJ, Dillane D, Sessler DI, Sieber F, Magaziner J, Marcantonio ER, Mehta S, Menio D, Ayad S, Stone T, Papp S, Schwenk ES, Elkassabany N, Marshall M, Jaffe JD, Luke C, Sharma B, Azim S, Hymes RA, Chin KJ, Sheppard R, Perlman B, Sappenfield J, Hauck E, Hoeft MA, Giska M, Ranganath Y, Tedore T, Choi S, Li J, Kwofie MK, Nader A, Sanders RD, Allen BFS, Vlassakov K, Kates S, Fleisher LA, Dattilo J, Tierney A, Stephens-Shields AJ, Ellenberg SS; REGAIN Investigators. Spinal Anesthesia or General Anesthesia for Hip Surgery in Older Adults. N Engl J Med. 2021 Nov 25;385(22):2025-2035. doi: 10.1056/NEJMoa2113514. Epub 2021 Oct 9.
• Neuman MD, Gaskins LJ, Ziolek T; REGAIN Investigators. Time to institutional review board approval with local versus central review in a multicenter pragmatic trial. Clin Trials. 2018 Feb;15(1):107-111. doi: 10.1177/1740774517735536. Epub 2017 Oct 6.
• Neuman MD, Ellenberg SS, Sieber FE, Magaziner JS, Feng R, Carson JL; REGAIN Investigators. Regional versus General Anesthesia for Promoting Independence after Hip Fracture (REGAIN): protocol for a pragmatic, international multicentre trial. BMJ Open. 2016 Nov 15;6(11):e013473. doi: 10.1136/bmjopen-2016-013473.

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): June 1, 2021
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: July 21, 2015
• First Submitted That Met QC Criteria: July 23, 2015
• First Posted (Estimate): July 24, 2015

Study Record Updates

• Last Update Posted (Actual): January 11, 2022
• Last Update Submitted That Met QC Criteria: January 7, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Leg Injuries; Femoral Fractures; Hip Injuries; Fractures, Bone; Hip Fractures; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics
• Other Study ID Numbers: 822632; PCORI-1406-18876 (Other Grant/Funding Number: PCORI)