Clinical trial NCT02602704: Effectiveness of Bazedoxifene for Prevention of Glucocorticoid-induced Bone Loss in RA Patients
Official title: Effectiveness of Bazedoxifene for Prevention of Glucocorticoid-induced Bone Loss in RA Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Arthritis, Rheumatoid
Lead sponsor: Hanyang University
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2015-11-11
Enrollment: 114
Sex: FEMALE
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: * The purpose of this study is to study the effectiveness of bazedoxifene in preventing loss of bone mineral density (BMD) and trabecular bone score (TBS), and any fractures in postmenopausal rheumatoid arthritis (RA) patients receiving long-term GCs.
* This is a randomized, controlled, open-label extension study for 48 or 56 weeks. At study entry, all patients will receive elemental calcium (1200 mg daily) and vitamin D (800 IU daily) and will be randomized by blocks of two to receive either bazedoxifene (20 mg/day) or none.

Detailed description: * The purpose of this study is to study the effectiveness of bazedoxifene in preventing loss of bone mineral density (BMD) and trabecular bone score (TBS), and any fractures in postmenopausal rheumatoid arthritis (RA) patients receiving long-term GCs.
* This was a randomized, controlled, open-label study conducted for 56 weeks. Four trial visits occurred over the course of the 56 weeks. At study entry, all patients who took elemental calcium (1200 mg daily) and vitamin D (800 IU daily) were assigned by blocks of two to receive either bazedoxifene (20 mg/day) (bazedoxifene group) or not (control group).
* Randomization was performed by an independent coordinator. Participants were followed-up at 24 weeks and 48 weeks with special attention to RA flares and occurrence of AEs.
* Demographic characteristics such as age, sex, and medications related to RA, as well as laboratory result such as complete blood count (CBC), chemistry, and levels of inflammatory markers were collected at enrollment. BMD and trabecular bone score (TBS) were assessed at 0 and 48 weeks, and levels of bone turnover markers were assessed at 0, 24, and 48 weeks. At 56 weeks, the occurrence of AEs was assessed.

Eligibility criteria: Inclusion Criteria:

* Female RA patients ≥ 45 years old with self-reported postmenopausal for ≥12 months or prior hysterectomy with bilateral oophorectomy. Female patients ≥ 55 years old who had prior hysterectomy without oophorectomy or with unilateral oophorectomy.
* Having been receiving low to moderate dose of glucocorticoids (prednisone ≤7.5 mg/day or equivalent) for ≥3 months prior to entry. (When taking glucocorticoids PRN, prednisone ≥1mg/day in average.)
* Patients expected to be on glucocorticoid treatment for 3 months after entry.
* Patients with an osteopenic mean lumbar spine (LS; L1-L4) or femoral neck bone mineral density (BMD; -1 \< T-score \< -2.5)
* Patients who provide a written consent of participating in this study.

Exclusion Criteria:

* Patients with condition that may interfere with the evaluation of spinal or hip osteoporosis by DXA such as two or more vertebral (L1-L4) fractures or other vertebral deformity
* Patients with hypercoagulability risk factors or a history of deep vein thrombosis and pulmonary embolism
* History of allergic reactions or intolerance to bazedoxifene or other SERM
* Patients receiving bisphosphonates, parathyroid hormone, SERMs, or anticonvulsants therapies within 6 months prior to entry
* Patients with known bone disorders such as osteomalacia, renal osteodystrophy and hyperparathyroidism
* Patients with undiagnosed uterine bleeding
* Patients with severe renal impairment or creatinine clearance \<30ml/min

Primary outcomes:
measure: Change of Bone Mineral Density (BMD)
timeFrame: Baseline and 48 weeks
Secondary outcomes:
measure: Change of Trabecular Bone Score (TBS)
timeFrame: Baseline and 48 weeks
measure: Development of the thoracic and lumbar vertebrae for deformities by visual inspection
timeFrame: Baseline and 48 weeks
measure: Development of any fractures including nonvertebral fractures
timeFrame: Baseline, 24 weeks and 48 weeks
measure: Change in serum C-terminal telopeptide (CTX)
timeFrame: Baseline, 24 weeks and 48 weeks
measure: Change in urine N-telopeptide (NTX)
timeFrame: Baseline, 24 weeks and 48 weeks
measure: Change in serum bone specific alkaline phosphatase
timeFrame: Baseline, 24 weeks and 48 weeks
measure: Change in serum osteocalcin
timeFrame: Baseline, 24 weeks and 48 weeks
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Hanyang University
Study officials:
affiliation: Hanyang University Hospital for Rheumatic Diseases
name: Yoon-Kyoung Sung, MD, PhD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cho SK, Kim H, Lee J, Nam E, Lee S, Choi YY, Sung YK. Effectiveness of bazedoxifene in preventing glucocorticoid-induced bone loss in rheumatoid arthritis patients. Arthritis Res Ther. 2021 Jul 2;23(1):176. doi: 10.1186/s13075-021-02564-1.