Clinical trial NCT04796350: RESTORE - Study of AGN1 LOEP to Prevent Secondary Hip Fractures
Official title: Randomized Controlled Study of a Local Osteo-Enhancement Procedure (LOEP) to Prevent Secondary Hip Fractures in Osteoporotic Women Undergoing Treatment of Index Hip Fractures
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Fragility Fracture
Hip Fractures
Osteoporosis
Keywords: Osteoporosis
Hip Fracture
Fragility Fracture
LOEP
RESTORE
Local osteo-enhancement procedure
Lead sponsor: AgNovos Healthcare, LLC
Sponsor class: INDUSTRY
Collaborators: name: Avania
name: CMIC Co, Ltd. Japan
name: BioClinica, Inc.
name: Emergent Clinical Consulting, LLC
First posted: 2021-03-12
Enrollment: 2400
Sex: FEMALE
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: A randomized controlled trial to evaluate AGN1 to prevent secondary hip fractures in osteoporotic women undergoing treatment of index hip fractures. Up to 2400 subjects will be randomized between a treatment group and a control group. Subjects will be followed for a minimum of 5 years after undergoing hip fracture repair surgery.

Detailed description: This is an event driven, randomized, controlled, prospective, single blinded (non-blinded in Canada), multi-national study.

This study is designed to demonstrate that the AGN1 LOEP treatment can reduce the incidence of secondary hip fractures in subjects presenting with an index hip fracture and undergoing hip fracture repair surgery. Subjects presenting with an index fragility hip fracture who will undergo hip fracture repair will be enrolled. Subjects will be randomized 1:1 into the following two study groups:

1. Treated Group - receives standard of care to repair the index hip fracture and AGN1 LOEP treatment on the target unfractured contralateral hip
2. Control Group - receives standard of care to repair the index hip fracture and no AGN1 LOEP treatment on the target unfractured contralateral hip

AGN1 LOEP is an elective procedure that will be performed immediately following hip fracture repair.

Subjects will be followed through scheduled visits conducted at 6 weeks, 6 months, and every 6 months thereafter for a minimum of 5 years.

Eligibility criteria: Inclusion Criteria:

1. Subject is a postmenopausal female at least 1-year post menses and at least 65 years of age.
2. Subject presents with a low-energy index fragility hip fracture in one hip and will undergo surgical repair of the fractured hip.
3. Subject has at least one of the following additional risk factors for a secondary hip fracture (as determined by subject or legally authorized representative (LAR) interview or medical record review):

   * Documented falls assessment indicating subject is at moderate or high risk of falls
   * Falls history (2 or more falls in the previous 12 months)
   * History of vertigo, dizziness, or postural hypotension
   * Documented T-score \< -2.5 at the hip
   * Taking more than 3 daily prescription medications
   * Visual impairment as confirmed by one of the following:

     * Subject reports difficulty seeing
     * Lack of depth perception or vision loss in one eye
     * Macular degeneration
     * Cataracts
   * Prior non-hip fragility fracture
   * Cognitive frailty as assessed by SPMSQ (mild or moderate cognitive impairment) or delirium
   * Parkinson's disease stage 3 or 4
   * 10-year hip fracture probability \>15% using the FRAX® Fracture Risk Assessment Tool of the clinical site country
4. Subject is expected to be ambulatory after the hip fracture repair procedure.
5. Informed consent is provided by the subject or the subject's LAR.
6. The subject's willingness, ability, and commitment to participate in screening, treatment, and all follow-up evaluations for the full duration of the study has been documented.

Exclusion Criteria:

1. Subject hospital admission is \> 24 hours from the time of the index hip fracture.
2. Subject was dependent on the use of a wheelchair or was bedridden prior to the index hip fracture.
3. Subject is currently enrolled in another clinical study.
4. Subject has a history of hip surgery or previous hip fracture on the target unfractured hip contralateral to the index hip fracture.
5. Subject has one or more new fractures in addition to the index hip fracture at admission that, in the opinion of the investigator, would further compromise patient mobility, rehabilitation, and/or recovery or subject has three or more new fractures in addition to the index hip fracture.
6. Subject has an infection at the LOEP intended treatment site or has non-intact skin or acute traumatic injuries with open wounds close to the area of intended LOEP treatment.
7. Subject has a progressive increase in undiagnosed pain in the target hip contralateral to the index fractured hip over the previous 3 months that in the opinion of the Investigator may suggest underlying bone or joint pathology on the unfractured side.
8. Subject has radiological evidence of gross bony or joint pathology of the hip, including signs predictive of atypical femoral fractures (e.g. cortical beaking), or has been diagnosed and/or treated for atypical femoral fractures.
9. Subject is at ASA Class IV, V, or VI.
10. Subject has a history of metabolic bone disease other than osteoporosis (e.g., Paget's disease, renal osteodystrophy, or osteomalacia).
11. Subject has a history of Pott's disease.
12. Subject has a history of any invasive malignancy (except nonmelanoma skin cancer), unless treated with curative intent and with no clinical signs or symptoms of the malignancy for 5 years.
13. Subject has chronic cardiac insufficiency or severe cardiovascular disease as assessed by a subject or LAR interview to be NYHA Class III or IV or has an implanted pacemaker.
14. Subject has a history of cardiovascular events (e.g. stroke, transient ischemic attack, myocardial infarction, unstable angina, pulmonary embolus, deep vein thrombosis, ventricular tachycardia, or atrial fibrillation) in the last 3 months.
15. Subject is on oral or parenteral immuno-suppressive drugs.
16. Subject has uncontrolled diabetes mellitus.
17. Subject has Hb ≤ 9 g/dL at admission.
18. Subject has severe renal insufficiency defined as an estimated glomerular filtration rate (eGFR) ≤ 30 mL/min.
19. Subject has a diagnosed and ongoing calcium metabolism disorder.
20. Subject has a Parker Mobility Score ≤ 5.
21. Subject has severe cognitive impairment as assessed by SPMSQ.
22. Subject has known allergies to calcium-based bone void fillers.
23. In the judgement of the Investigator, the subject is not a good study candidate (e.g., inability to maintain follow-up schedule, comorbidity or poor general physical/mental health, or drug or alcohol abuse issues).
24. Subject fails pre-operative or intraoperative eligibility criteria as specified in section 7.4.2. of the clinical investigation plan.

Primary outcomes:
measure: Cumulative incidence of secondary fragility hip fractures
timeFrame: Interim Analysis, approximately 30 Months
measure: Cumulative Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Interim Analysis, approximately 30 Months
Secondary outcomes:
measure: Areal bone mineral density (aBMD)
timeFrame: 12 months and 24 months
measure: Trabecular Bone Score (TBS)
timeFrame: 12 months and 24 months
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Innsbruck Hospital
city: Saint John's
country: Canada
facility: Health Sciences Centre - Eastern Health
state: Newfoundland and Labrador
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Grenoble
country: France
facility: CHU Grenoble-Alpes
city: Lyon
country: France
facility: CHU Lyon
city: Toulouse
country: France
facility: CHU Toulouse
city: Düsseldorf
country: Germany
facility: University Hospital of Duesseldorf
city: Gießen
country: Germany
facility: Justus Liebig Universitat Gießen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Kiel
country: Germany
facility: Universitatsklinikum Schleswig-Holstein
city: München
country: Germany
facility: Klinikum der Universität München
city: Münster
country: Germany
facility: University Hospital of Münster
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg
city: Tuebingen
country: Germany
facility: BG Klinik Tuebingen
city: Wuppertal
country: Germany
facility: Helios Wuppertal
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi
city: Milano
country: Italy
facility: ASST Gaetano Pini CTO
city: Milano
country: Italy
facility: University Hospital San Raffaele Milano
city: Rome
country: Italy
facility: Policlinico Tor Vergata
city: Torino
country: Italy
facility: CTO Torino
city: Akita-shi
country: Japan
facility: Akita City Hospital
state: Akita
city: Kōriyama
country: Japan
facility: Southern Tohoku General Hospital
state: Fukushima
city: Nishinomiya
country: Japan
facility: Hyogo Prefectural Nishinomiya Hospital
state: Hyogo
city: Marugame
country: Japan
facility: Kagawa Rosai Hospital
state: Kagawa
city: Kawasaki City
country: Japan
facility: Kanto Rosai Hospital
state: Kanagawa
city: Kawasaki-Shi
country: Japan
facility: Shin-yurigaoka General Hospital
state: Kanagawa
city: Kouchi City
country: Japan
facility: Chikamori Hospital
state: Kochi
city: Okayama City
country: Japan
facility: Okayama Medical Center
state: Okayama
city: Izunokuni City
country: Japan
facility: Jutendo University Shizuoka Hospital
state: Shizuoka
city: Bunkyō-Ku
country: Japan
facility: The University of Tokyo Hospital
state: Tokyo
city: Fukuoka
country: Japan
facility: St. Mary's Hospital
city: Iwata
country: Japan
facility: Iwata City Hospital
city: Kawasaki-shi
country: Japan
facility: Shin-Yurigaoka General Hospital
city: Kumamoto
country: Japan
facility: National Hospital Organization Kumamoto Medical Center
city: Saga
country: Japan
facility: Saga-Ken Medical Centre Koseikan
city: Shizuoka
country: Japan
facility: Japanese Red Cross Shizuoka Hospital
city: Deventer
country: Netherlands
facility: Deventer Hospital
city: Geldrop
country: Netherlands
facility: Saint Anna Ziekenhuis
city: Maastricht
country: Netherlands
facility: Maastricht UMC
city: Zwolle
country: Netherlands
facility: Isala Hospital
city: Barcelona
country: Spain
facility: Vall d'Hebron University Hospital
city: Barcelona
country: Spain
facility: Clinic de Barcelona
city: Bilbao
country: Spain
facility: Hospital Universitario de Basurto
city: Galdakao
country: Spain
facility: Galdakao-Usansolo Hospital
city: Jaén
country: Spain
facility: Hospital Neuro-Traumatológico de Jaén
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Sabadell
country: Spain
facility: PARC Tauli
city: Terrassa
country: Spain
facility: Mutua de Terrassa University Hospital
city: Valladolid
country: Spain
facility: Valladolid University Clinic Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
state: Scotland
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals, Queen's Medical Center
Study officials:
References: