Improving Community Ambulation After Hip Fracture: Protocol for a Randomized Controlled

The CAP Study

Improving Community Ambulation after Hip Fracture: Protocol for a randomized controlled trialcomparing two physical therapy interventions

Authors: D Orwig1, KK Mangione2, M Baumgarten1, M Terrin1, R Fortinsky3, AM Kenny4, AL Gruber-Baldini1, B Beamer5,6, ANA Tosteson7,8, M Shardell9, L Magder1, E Binder10, K Koval11, B Resnick12, RL Craik2, J Magaziner1

Institutional affiliations: 1Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD; 2Department of Physical Therapy, College of Health Sciences, Arcadia University, Glenside, PA; 3UConn Center on Aging, UConn Health, Farmington, CT; 4Department of Medicine, UConn Health, Farmington, CT; 5Gerontology Research, Education and Clinical Center (GRECC) at Baltimore Veterans Affairs Medical Center, and 6Division of Geriatric Medicine and Gerontology at University of Maryland School of Medicine; 7Department of Medicine and 8The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine at Dartmouth, Hanover, NH; 9National Institute on Aging, National Institutes of Health, Baltimore, MD; 10Division of Geriatrics and Gerontology, Washington University School of Medicine, St Louis, MO;11Department of Orthopaedic Surgery, Orlando Regional Medical Centre, Orlando, FL; 12University of Maryland School of Nursing, Baltimore, MD.

Abstract: 730words

Introduction:After a hip fracture in older persons, significant disability often remains; dependency in functional activities persists beyond three months post-surgery.Endurance, dynamic balance, quadriceps strength, and function are compromised and contribute to failure of hip fracture patients’ ability to walk independently in the community. In the United States, people 65 years and older are eligible to receive Medicare funding for physical therapy for a limited time after a hip fracture. A goal of outpatient physical therapy is independent, safe household ambulation two to three months after surgery.Current Medicare-reimbursed post-hip fracture rehabilitation fails to return many patients to pre-fracture levels of function.Interventions delivered in the home after usual hip fracture physical therapy care ends could promote higher levels of functional independence in these frail, older adult patients.

Primary Objective:To evaluate the effect of a specific multi-component physical therapy intervention (PUSH),compared to a non-specific multi-component control physical therapy intervention (PULSE), on the ability to ambulate independently in the community 16 weeks post-randomization.

Design:Parallel, two-group randomized multi-center trial of 210 older adults witha hip fracture assessedat baseline and at 16 weekspost-randomization, and at 40 weeks post randomization for a subset of approximately 150 participants.

Participants and Setting: 210 hip fracture patients are beingenrolled at three clinical sites and randomized up to 26 weeks post-admission. Study inclusion criteria are: 1) Closed, non-pathologic, minimal trauma hip fracture with surgical fixation; 2) Age ≥60 years at time of randomization; 3) Community-residing at time of fracture and randomization; 4) Ambulating without human assistance two months prior to fracture; and 5) Unable to walk at least 300 m in six minutes at baseline. Participants are ineligible if the interventions are deemed to be unsafe or not feasible, or if the participant has low potential to benefit from the interventions.

Interventions: Participants are randomly assigned to one of two multi-componenttreatment groups: 1) PUSH or 2) PULSE. PUSH is based on aerobic conditioning, specificity of training, and muscle overload, while PULSE includes transcutaneous electrical nerve stimulation, flexibility activities, and active range of motion exercises.Participants in both groups receive 32 visits in their place of residence from a study physical therapist (PT) (2 visits per week on non-consecutive days for 16 weeks). PTs’ adherence to the treatment protocol, and participants’ receipt of the prescribed activities, are assessed. Participants also receive counseling from a registered dietician and vitamin D, calcium and multivitamin supplements during the 16-week intervention period.

Measurements: The primary outcome (community ambulation)is operationalized as the ability to walk 300 m or more in six minutes, as assessed by the Six-Minute Walk Test, at 16 weeks post-randomization. Other measures at 16 and 40 weeks include cost-effectiveness, endurance, dynamic balance, walking speed, quadriceps strength, lower extremity function, activities of daily living, balance confidence, quality of life, physical activity, depressive symptoms, increase of ≥50 m in distance walked in six minutes, cognitive status, and nutritional status.

Analysis: Analyses for all aims will be performed according to the intention-to-treatparadigm. Except for testing of the primary hypothesis, all statistical tests will be two-sided and not adjusted for multiple comparisons. The test of the primary hypothesis (comparing groups onthe proportion who are community ambulators at 16 weeks post-randomization) will be based on a one-sided 0.025-level hypothesis test using a procedure consisting of four interim analyses and one final analysis with critical values chosen by a Hwang-Shih-Decani alpha-spending function. Analyses will be performed to test group differencesonother outcome measures and to examine the differential impact of PUSH relative to PULSE in subgroups defined by pre-selected participant characteristics. Generalized estimating equations will be used to explore possible delayed or sustained effects in a subset of participants by comparing the difference between PUSH and PULSE in the proportion of community ambulators at 16 weeks with the difference at 40 weeks.

Discussion:This multi-center randomized study will be the first to test whether a home-based multi-componentphysical therapyintervention targeting specific precursors of community ambulation (PUSH) is more likely to lead to community ambulation than a home-based non-specific multi-component PT intervention (PULSE) in older adults after hip fracture. The study will also estimatethe potential economic value of the interventions.

Trial registration: clinicaltrials.gov

Registration number: NCT01783704

Was this trial prospectively registered? Yes

Date of trial registration: 01/31/2013

Funded by: National Institute on Aging

Funder approval number: R01 AG035009

Anticipated completion date:April 2018

Corresponding author contact details:

Denise Orwig, Ph.D.

Associate Professor

Director, Baltimore Hip Studies

University of Maryland School of Medicine

Department of Epidemiology & Public Health

660 West Redwood Street, Suite 200

Baltimore, MD 21201

410-706-2406

410-706-4433 (fax)

Improving Community Ambulation after Hip Fracture: Protocol for a randomized controlled trial comparing two physical therapy interventions

Human research approval committees:

University of Maryland, Baltimore Institutional Review Board (StudyOversight): HP-00046956

Arcadia University Institutional Review Board: 12-08-01

University of Maryland, Baltimore Institutional Review Board (University of Maryland, Baltimore Clinical Site): HP-00052790

University of Connecticut Health Center Institutional Review Board: IE-13-041HSF-3

INTRODUCTION

In the US, standard Medicare-reimbursed rehabilitation therapy fails to restore community ambulation to older persons who have had a hip fracture. Residual mobility disability similar to that reported after stroke occurs in the majority of persons who “recover” from hip fracture.1,2Even though there are over 325,000 hip fractures per year in the US3,4 with a predicted increase to over 650,000 per year by 2040,5there is a paucity of intervention trials in this patient population. The estimated cost to hip fracture patients, their families, and the health care system is between $14 and $20 billion annually.6-11

The goal of current rehabilitation practice is independent, safe household ambulation two to three months after surgery.12 Hip fracture-acquired dependency in functional activities of daily living persists well beyond three months post-surgery.Twenty percent of patients have been reported to need help putting on pants, 50% need assistance to walk, and 90% need assistance to climb stairs one year post-fracture.13 A Cochrane Collaboration review on exercise interventions post-hip fracture (13 clinical trials including 1,065 participants) concluded that there is insufficient evidence to determine if the evaluated interventions substantially reduce residual disability and enhance community ambulation.14

Community ambulation is associated with fivephysical precursors: endurance, dynamic balance,quadriceps strength, walking speed, and lower extremity function.15,16In two studies, one of older adults with hip fracture and one among frail community-residing older adults without hip fracture, the most successful interventions in terms of improving strength, balance, and gait speed were completed over a 6-month time period in an exercise center.17,18 Interventions included various combinations of strengthening exercise, balance training, functional training, and active range of motion (AROM) and flexibility. Results show positive outcomes in terms of function, gait speed, balance, strength, and endurance.17-24However, there is no evidence regarding the effectiveness of delivering a similarly intense multi-component intervention in the home. Mangione reported dramatic improvements in physical precursors to community ambulation using an intervention that provided function, strength, balance, and endurance training in a single patient three months post-hip fracture and as soon as usual home care was complete.25

The Community Ambulation Project (CAP) was designed to determine whether a specific multi-component 16-week intervention based on specificity of training and overload (the PUSH intervention) delivered in the home and initiated up to 26 weeks following hospital admission for hip fracture, will be successful in producing community ambulation (ability to walk a distance of 300 m or more in 6 minutes) at 16 weeks after randomization. We will compare PUSH to a non-specifichome-based multi-component intervention of sensory level electrical stimulation, flexibility and active range of motion (AROM) exercises (the PULSE intervention).We are testing the hypothesis that a greater proportion of PUSH participants than PULSE participants will achieve community ambulation 16 weeks after randomization. In addition, the cost-effectiveness of the interventions as well as effects on other outcomes will be examined.

METHODS

Study Organization

This multi-center randomized controlled trial (RCT) has a Clinical Coordinating Center, a Data Coordinating Center, an Economic Evaluation Core, and three clinical sites. In addition to these units, the project has a Steering Committee and three Scientific Oversight Committeesthat provide expertise needed to conduct this investigation. Members of the Data and Safety Monitoring Board (DSMB) were appointed by and report to the National Institute on Aging (NIA) which is the funding agency.The DSMB monitors participant safety; evaluates the progress of the study; reviews procedures for maintaining confidentiality, quality of data collection, statistical analysis plans, and results of interim analyses in accordance with pre-specified stopping guidelines.

Study Design

This is arandomized, parallel,two-group multi-center RCT of 210 older adults who have experienced a hip fracture.Half of the participantsreceivesa specific multi-component intervention (PUSH) and the other half receives a non-specific multi-component intervention (PULSE). Patients age 60 years and older who have had surgical repair for hip fracture are identified at three clinical sites (Arcadia University-AU, University of Maryland, Baltimore- UMB, and University of Connecticut Health Center- UCHC). Following consent to participate after hospital discharge, eligible participants undergo a comprehensive baseline assessment and are randomized to one of the two treatment groups. Participants are assessed again 16 weeks post-randomization. Figure 1 shows the sequence of participant contacts.For participants randomized prior to the current version of the protocol, follow-up assessment visits also occurred at 40 weeks from the date of randomization and telephone interviews were conducted every four weeks during the full 40-week study period.

Within a week of randomization, a physical therapist (PT) initiates the intervention in the participant’s place of residence and they receive counseling with a registered dietician. Participants receive calcium, vitamin D, and multivitamin supplements during the 16-week intervention period. A $20 honorarium is given to the participant at the completion of the each of the three assessment visits.

Figure 1. Participant timeline for screening, randomization, and follow-up

Recruitment Procedures, Setting, and Participants

Most potential participants are identified by CAP staff at study hospitals, rehabilitation centers, and other agencies that care for older adults. A smaller number of participants are recruited through the use of flyers, advertisements, social media, or referral from an orthopedic surgeon or physical therapist.

Eligibility Screening

Participants are evaluated for eligibility in three phases completed no later than 26 weeks after admission to the hospital for hip fracture. Patients identified in acute care hospitals, and who are provisionally eligible based on medical chart review (phase 1),are approached in the hospital (or soon after discharge) and told about the study. Written permission from the patient (or the legally authorized representative) is obtained to allow future contact to collect additional eligibility information. Patients who are identified through means other than screening in study hospitals are asked to provide written authorization for release of medical records to review for eligibility (phase 1) criteria.

The participant is assessed for medical, safety, and feasibility criteriaduring phase 2. Written informed consent is obtained during the phase 2 assessment.Blood is collected no more than 4 weeks prior to randomization and is tested for hemoglobin, serum creatinine and serum albumin.

Prior to the phase 3 visit, a medical provider familiar with the patient since the hip fracture (e.g., primary care physician, orthopedic surgeon, etc.) reviews the potential participant’s medical history and confirms safety for participation. Phase 3 eligibility screening is performed during the baseline visit which is conducted at the clinical site. Screening for final eligibility includes a review for all disqualifying medical conditions, assessment of cognitive status with the Modified Mini-Mental State examination (3MS), and evaluation of ability to walk 300 m or more in six minutes (using the SMWT).

Inclusion and Exclusion Criteria

Participants are included if they had a minimal trauma, closed, non-pathologic hip fracture with surgical repair, are age 60 years or older at time of randomization, were living in the community at time of fracture and randomization, were ambulating without human assistance two months prior to fracture, and are unable to walk 300 m or more in six minutes at baseline.

Patients who are not able to provide their own informed consent to participate in the study are not eligible. Patients are excluded if they have end stage renal disease, recent myocardial infarction, chest pain or shortness of breath, uncompensated congestive heart failure, severely diminished lower extremity sensation or ulceration, symptoms of angina, or uncontrolled hypertension or if they are not fully weight bearing on either leg. Patients are ineligible if they develop chest pain, intolerable dyspnea, or severe pain during the SMWT, if it takes >40 seconds to walk the first four meters of the SMWT, or if serum albumin is less than 2.5 g/dL, hemoglobin is less than 9 g/dL, or calculated creatinine clearance is less than 15 ml/min. Furthermore, patients are not eligible if they are receiving physical therapy in a hospital or inpatient rehabilitation facility at the time of randomization, are cognitively impaired(Modified Mini-Mental State Exam (3MS) score <73),25,26are not English speaking, do not live within a reasonable distance of the clinical site, are participating in another clinical trial, or plan to move out of the area during the 16-week intervention period. Patients are not eligible if medical clearance is denied by the patient’s medical provider or if the clinical site clinician thinks the patient is not a good candidate for the trialdue to having medical conditions that would prohibit safe participation in the trail (e.g., advanced progressive neuromuscular diseases such as severe Parkinson’s disease or multiple sclerosis, uncontrolled psychoses, or unstable cardiovascular disease) or if the patient is not likely to survive study period. Finally, patients are not eligible if they are community ambulators (walk ≥300 m in six minutes) at baseline or if randomization has not occurred by the end of the 26th week post-admission.

Informed Consent

Written informed consent and appropriate HIPAA authorizations and/or waivers are obtained in compliance with procedures reviewed and approved by each clinical site’s Institutional Review Board(IRB) prior to data collection. Potential participants who choose to enroll are assessed for their ability to provide informed consent using a local IRB-approved method. Individuals who do not understand the study purpose, the voluntary nature of the study, what will be asked of them during the study, and study risks are not eligible for participation.

Demographic and Surgical Characteristics

For descriptive purposes, information on the following participant characteristics is collected either during screening or at the baseline assessment: age, gender, race, living situation, marital status, educational level, fracture type, surgery type, height and weight. Other characteristics include the Functional Comorbidity Index which is a clinically based measure of 18 comorbidities developed by Groll et al.,27 the Life Orientation Test-Revised (LOT-R) to assess self-reported optimism and pessimism,28 and the Brief Resilience Scale to assess self-reported ability to bounce back after a stressful event.29

Randomization Procedures

The randomization schedule for each clinical site ensures that treatments are randomly assigned within blocks of 2, 4, 6, or 8, with equal numbers of participants assigned to each treatment within each block. Block sizes are randomly selected with the probability of each block size specified by the data coordinating center.

Randomization is performed by unblinded study staff, the clinical site principal investigator or the clinical site coordinator, using a secure Web-based randomization system. The study staff member accesses the system by logging in to a secure Web site and receives the treatment assignment after responding to prompts confirming that the participant meets all inclusion and exclusion criteria and has given informed consent for enrollment.

Interventions

Participants are assigned to one of two treatment groups: PUSH or PULSE. Both groups receive 32 visits of approximately 60 minutes duration from a study PT in the participant’s place of residence. Participants receive two visits per week, on non-consecutive days, for 16 weeks. Missed visits in a given week can be replaced by makeup visits on non-consecutive days in subsequent weeks. At the start of the study, PTs were randomly assigned by the DCC to deliver one of the two interventions within strata defined by geographic area. When there is staff turnover, newly hired PTs are assigned to the intervention group and geographic area of the PT whom they are replacing.

The PTs are trained in intervention-specific face-to-face sessions with the Intervention Monitor (IM). The training includes one half day of didactic instruction, skills practice with the equipment, and live videotaped performance of the procedures with older adult volunteers. The intervention manual of proceduresis reviewed throughout the session. PTs are certified after they demonstrate competence (90% passing score) on a written exam and video observation.