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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01081678




Registration number
NCT01081678
Ethics application status
Date submitted
4/03/2010
Date registered
5/03/2010
Date last updated
2/05/2019

Titles & IDs
Public title
Study To Assess FRacTure Healing With SclerosTin Antibody - Hip
Scientific title
A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Determine the Efficacy, Safety, and Tolerability of AMG 785 in Adults With a Fresh Unilateral Hip Fracture, Status Post Surgical Fixation
Secondary ID [1] 0 0
20080394
Universal Trial Number (UTN)
Trial acronym
STARTT-Hip
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fracture Healing 0 0
Condition category
Condition code
Injuries and Accidents 0 0 0 0
Fractures
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - Romosozumab

Placebo Comparator: Placebo - Participants received placebo to romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.

Experimental: Romosozumab 70 mg - Participants received 70 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.

Experimental: Romosozumab 140 mg - Participants received 140 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.

Experimental: Romosozumab 210 mg - Participants received 210 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.


Treatment: Drugs: Placebo
Administered by subcutaneous (under the skin) injection

Treatment: Drugs: Romosozumab
Administered by subcutaneous injection

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Timed-Up-and-Go (TUG) Over Week 6 Through Week 20 - Functional healing was measured by the timed-up-and-go test (TUG) over Weeks 6 through 20. During this assessment, the clinician timed the participant while they stood up from a seated position in a chair, walked three meters, turned around, walked three meters back to the chair, and returned to the seated position. A TUG value of ten seconds or less was considered normal for a healthy elderly person. Higher TUG values after hip fracture have been shown to be a predictor of future falls.
Least squares mean (LSM) estimates were based on a repeated measures model fitted with the log-transformed TUG values at weeks 2, 6, 12, 16, 20, 24, 36, 52 as the dependent variable and adjusted for treatment, randomized strata, gender, country category, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction and back-transformed using the exponential transformation.
Timepoint [1] 0 0
Weeks 6, 12, 16, and 20
Secondary outcome [1] 0 0
Timed-Up-and-Go (TUG) at Each Visit - During the timed-up-and-go test the clinician timed the participant while they stood up from a seated position in a chair, walked 3 meters, turned around, walked 3 meters back to the chair, and returned to a seated position. A TUG value of = 10 seconds is considered normal for a healthy elderly person.
LSMs were based on a repeated measures model adjusting for treatment, randomized strata, gender, country category, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction.
Missing TUG values for participants still on study were imputed using the last observation carried forward (LOCF) when possible. If no observation could be carried forward, the maximum TUG value observed among all participants at a given visit was used. TUG values obtained after unplanned revision surgery were replaced by carrying forward the last available observed or imputed value prior to unplanned revision surgery.
Timepoint [1] 0 0
Weeks 2, 6, 12, 16, 20, 24, 36, and 52
Secondary outcome [2] 0 0
Time to Radiographic Healing - Time to radiographic healing is the time interval from the surgery date for the eligible hip fracture to the date of radiographic healing, defined as effacement of the fracture lines by newly formed bone along the cortices and within the trabecular bone on anteroposterior and lateral (or oblique) radiographs. Radiographic fracture healing was determined by a panel of independent reviewers blinded to treatment.
The cumulative incidence function (CIF) method was used to estimate the median time to radiographic healing and the confidence intervals. Unplanned revision surgery to promote healing was considered a competing risk in CIF estimate.
Timepoint [2] 0 0
52 weeks
Secondary outcome [3] 0 0
Radiographic Union Scale for Hip (RUSH) Score At Each Visit - The radiographic Union Scale for Hip (RUSH) is a semiquantitative scoring assessment to assess hip fracture healing after surgical repair. The RUSH has 4 key domains based on radiographic parameters used by orthopedic surgeons and radiologists in routine clinical practice including cortical bridging (4 to 12 points), cortical fracture line disappearance (4 to 12 points), trabecular consolidation (1 to 3 points), and trabecular index disappearance of fracture line (1 to 3 points). The score has a minimum of 10 points (definitely not healed) and a maximum of 30 points (definitely healed).
Timepoint [3] 0 0
Weeks 2, 6, 12, 16, 20, 24, 36, and 52
Secondary outcome [4] 0 0
Harris Hip Score At Each Visit - The Harris Hip Score is a clinician-based outcome that assesses pain, function, deformity, and range of motion. The pain domain measures pain severity and its effect on activities and need for pain medication. The function domain consists of daily activities and gait. Deformity takes into account hip flexion, adduction, internal rotation, and extremity length discrepancy. Range of motion measures hip flexion, abduction, external and internal rotation, and adduction. The score ranges form 0-100 (best possible outcome) covering pain (0-44 points), function (0-47 points), absence of deformity (4 points), and range of motion (5 points). LSMs were based on a repeated measures model fitted with the Harris hip score values at weeks 2, 6, 12, 16, 20, 24, 36, and 52 as the dependent variable and adjusted for treatment, randomized strata, gender, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction.
Timepoint [4] 0 0
Weeks 2, 6, 12, 16, 20, 24, 36, and 52
Secondary outcome [5] 0 0
Hip Pain Score at Each Visit - Hip pain was assessed using a visual analog scale (VAS). Participants were asked to rate their pain as a result of the hip fracture on a 100 mm vertical scale with 0 indicating no pain at all and 100 indicating the worst pain they could imagine.
LSMs were based on a repeated measures model fitted with hip pain score values at weeks 2, 6, 12, 16, 20, 24, 36, and 52 as the dependent variable and adjusted for treatment, randomized strata, gender, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction.
Timepoint [5] 0 0
Weeks 2, 6, 12, 16, 20, 24, 36, and 52

Eligibility
Key inclusion criteria
- Males and females, age 55 to 95 years

- fresh unilateral low energy intertrochanteric or femoral neck fracture as the primary
injury, confirmed by X-ray and in the opinion of the treating surgeon amenable to
repair by internal fixation

- internal fixation of the fracture with devices approved by local regulatory agency,
performed no later than 7 days after injury for intertrochanteric or undisplaced
femoral neck fractures and no later than 2 days after injury for displaced femoral
neck fractures

- intertrochanteric fracture: sliding hip screw or IM nail

- femoral neck fracture: sliding hip screw or at least 3 cancellous screws
Minimum age
55 Years
Maximum age
95 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- severe symptomatic osteoarthritis of the lower extremity

- inability to independently rise from armchair or walk 200 meters before hip fracture

- presence of concomitant injuries such as rib fractures, wrist fractures, or acute
symptomatic vertebral fractures which severely impair the ability to rise from a chair

- associated extremity injuries including ipsilateral or contralateral fractures of the
foot, tibia or fibula, wrist, humerus, femoral shaft, femoral head or hip dislocation,
that may delay weight-bearing beyond one week after surgery

- head-injury, as defined by Glasgow Coma Scale < 13 prior to randomization

- use of bone grafts or bone substitutes at the time of fracture fixation

- major polytrauma or significant axial trauma, with Injury Severity Score > 16

- pathological fracture or history of metabolic or bone disease (except osteoporosis)
that may interfere with the interpretation of the results, such as Paget's disease,
rheumatoid arthritis, osteomalacia, osteopetrosis, ankylosing spondylitis, Cushing's
disease, hyperprolactinemia

- history of symptomatic spinal stenosis that has not been surgically corrected. If
surgically corrected, the subject must be asymptomatic to be eligible for the study.

- history of facial nerve paralysis

- malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma,
cervical carcinoma in situ) within the last 5 years

- history of solid organ or bone marrow transplants

- evidence of elevated transaminases (= 2.0 x upper limits of normal) or significantly
impaired renal function (creatinine clearance of = 30 mL/min)

- evidence of current hypercalcemia or hypocalcemia (outside of 1.1 x the normal range)

- bone morphogenic proteins (BMP)-2 or BMP-7 at the time of definitive fracture fixation

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Research Site - Liverpool
Recruitment hospital [2] 0 0
Research Site - Footscray
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
3011 - Footscray
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
Argentina
State/province [9] 0 0
Buenos Aires
Country [10] 0 0
Belgium
State/province [10] 0 0
Brugge
Country [11] 0 0
Belgium
State/province [11] 0 0
Genk
Country [12] 0 0
Belgium
State/province [12] 0 0
Leuven
Country [13] 0 0
Belgium
State/province [13] 0 0
Liege
Country [14] 0 0
Belgium
State/province [14] 0 0
Liège
Country [15] 0 0
Bulgaria
State/province [15] 0 0
Blagoevgrad
Country [16] 0 0
Bulgaria
State/province [16] 0 0
Pleven
Country [17] 0 0
Bulgaria
State/province [17] 0 0
Plovdiv
Country [18] 0 0
Canada
State/province [18] 0 0
Alberta
Country [19] 0 0
Canada
State/province [19] 0 0
Ontario
Country [20] 0 0
Canada
State/province [20] 0 0
Quebec
Country [21] 0 0
Denmark
State/province [21] 0 0
Hvidovre
Country [22] 0 0
Denmark
State/province [22] 0 0
København NV
Country [23] 0 0
Denmark
State/province [23] 0 0
Viborg
Country [24] 0 0
Denmark
State/province [24] 0 0
Ã…rhus C
Country [25] 0 0
Estonia
State/province [25] 0 0
Tallinn
Country [26] 0 0
Estonia
State/province [26] 0 0
Tartu
Country [27] 0 0
Finland
State/province [27] 0 0
Kuopio
Country [28] 0 0
Finland
State/province [28] 0 0
Oulu
Country [29] 0 0
Finland
State/province [29] 0 0
Turku
Country [30] 0 0
Germany
State/province [30] 0 0
Aachen
Country [31] 0 0
Germany
State/province [31] 0 0
Berlin
Country [32] 0 0
Germany
State/province [32] 0 0
Muenchen
Country [33] 0 0
Germany
State/province [33] 0 0
Muenster
Country [34] 0 0
Greece
State/province [34] 0 0
Athens
Country [35] 0 0
Greece
State/province [35] 0 0
Larissa
Country [36] 0 0
Greece
State/province [36] 0 0
Patra
Country [37] 0 0
Greece
State/province [37] 0 0
Thessaloniki
Country [38] 0 0
Hong Kong
State/province [38] 0 0
Hong Kong
Country [39] 0 0
Hong Kong
State/province [39] 0 0
New Territories
Country [40] 0 0
Hungary
State/province [40] 0 0
Budapest
Country [41] 0 0
Hungary
State/province [41] 0 0
Miskolc
Country [42] 0 0
Hungary
State/province [42] 0 0
Nyiregyhaza
Country [43] 0 0
Hungary
State/province [43] 0 0
Szeged
Country [44] 0 0
India
State/province [44] 0 0
Andhra Pradesh
Country [45] 0 0
India
State/province [45] 0 0
Karnataka
Country [46] 0 0
India
State/province [46] 0 0
Maharashtra
Country [47] 0 0
India
State/province [47] 0 0
Rajasthan
Country [48] 0 0
India
State/province [48] 0 0
Mangalore
Country [49] 0 0
India
State/province [49] 0 0
Nashik
Country [50] 0 0
Italy
State/province [50] 0 0
Firenze
Country [51] 0 0
Italy
State/province [51] 0 0
Milano
Country [52] 0 0
Italy
State/province [52] 0 0
Roma (RM)
Country [53] 0 0
Italy
State/province [53] 0 0
Verona
Country [54] 0 0
Latvia
State/province [54] 0 0
Riga
Country [55] 0 0
Latvia
State/province [55] 0 0
Valmiera
Country [56] 0 0
Lithuania
State/province [56] 0 0
Kaunas
Country [57] 0 0
Lithuania
State/province [57] 0 0
Vilnius
Country [58] 0 0
Netherlands
State/province [58] 0 0
Amsterdam
Country [59] 0 0
Netherlands
State/province [59] 0 0
Haarlem
Country [60] 0 0
Netherlands
State/province [60] 0 0
Nieuwegein
Country [61] 0 0
New Zealand
State/province [61] 0 0
Christchurch
Country [62] 0 0
Poland
State/province [62] 0 0
Kraków
Country [63] 0 0
Poland
State/province [63] 0 0
Lublin
Country [64] 0 0
Poland
State/province [64] 0 0
Warszawa
Country [65] 0 0
Slovenia
State/province [65] 0 0
Celje
Country [66] 0 0
Slovenia
State/province [66] 0 0
Izola
Country [67] 0 0
Slovenia
State/province [67] 0 0
Jesenice
Country [68] 0 0
Slovenia
State/province [68] 0 0
Sempeter pri Gorici
Country [69] 0 0
Sweden
State/province [69] 0 0
Linköping
Country [70] 0 0
Sweden
State/province [70] 0 0
Lund
Country [71] 0 0
Switzerland
State/province [71] 0 0
Basel
Country [72] 0 0
Switzerland
State/province [72] 0 0
Lausanne
Country [73] 0 0
Switzerland
State/province [73] 0 0
Luzern
Country [74] 0 0
Switzerland
State/province [74] 0 0
Zurich
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Barnet
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Leeds
Country [77] 0 0
United Kingdom
State/province [77] 0 0
London
Country [78] 0 0
United Kingdom
State/province [78] 0 0
Newcastle
Country [79] 0 0
United Kingdom
State/province [79] 0 0
Norwich

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is an international, multi-center study to determine the efficacy, safety, and
tolerability of romosozumab (AMG 785) in adults with a fresh unilateral hip fracture, status
post surgical fixation.
Trial website
https://clinicaltrials.gov/show/NCT01081678
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications