このページは自動翻訳されたものであり、翻訳の正確性は保証されていません。を参照してください。 英語版 ソーステキスト用。

Sequential Treatment With Romosozumab Followed by Denosumab vs. Zoledronic Acid for Gains in HIP BMD (STRONG-HIP)

2026年8月18日 更新者：Mattias Lorentzon、Sahlgrenska University Hospital

Short-course Romosozumab Followed by Denosumab Versus Zoledronic Acid: A Multicentre Randomized Active-controlled Trial in Postmenopausal Women at High Fracture Risk

Osteoporosis is associated with a high risk of fractures, disability, loss of independence, and excess mortality. Zoledronic acid is an established first-line treatment in Sweden, but many patients at high fracture risk remain at substantial residual fracture risk. Short-course treatment with romosozumab followed by denosumab produces large increases in bone mineral density, but has not been directly compared with zoledronic acid.

STRONG-HIP is a multicentre, randomized, active-controlled phase 4 trial in 216 postmenopausal women aged 60 years or older with osteoporosis and high fracture risk. Participants are randomized 1:1 to receive romosozumab 210 mg monthly for 3 months followed by denosumab 60 mg every 6 months, or zoledronic acid 5 mg intravenously at baseline and Month 12.

The primary objective is to determine whether the romosozumab-denosumab sequence produces a greater percentage increase in total hip bone mineral density from baseline to Month 24 than zoledronic acid. Secondary outcomes include total hip and lumbar spine BMD at earlier time points, vertebral and clinical fractures, bone turnover markers, safety, health-related quality of life, and health-economic outcomes. A mechanistic substudy will assess bone microarchitecture and estimated strength using HR-pQCT.

Participants are followed for 24 months in the main study and may enter an optional extension with follow-up to Month 48 to assess the durability of treatment effects.

調査の概要

状態

まだ募集していません

条件

介入・治療

研究の種類

介入

入学 (推定)

216

段階

  • フェーズ 4

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究連絡先のバックアップ

研究場所

  • スウェーデン
    • Skåne County
      • Malmö、Skåne County、スウェーデン、20502
        • Skåne Universitetssjukhus
        • コンタクト：
    • Stockholm County
      • Huddinge、Stockholm County、スウェーデン、14186
        • Karolinska University Hospital Huddinge
        • コンタクト：
      • Stockholm、Stockholm County、スウェーデン、11361
    • Uppsala County
      • Uppsala、Uppsala County、スウェーデン、751 85
    • Västerbotten County
      • Umeå、Västerbotten County、スウェーデン、90185
    • Västernorrland County
      • Sundsvall、Västernorrland County、スウェーデン、856 43
    • Västra Götaland County
      • Mölndal、Västra Götaland County、スウェーデン、43180
        • Sahlgrenska University Hospital Mölndal
        • コンタクト：
      • Skövde、Västra Götaland County、スウェーデン、54949
    • Östergötland County
      • Linköping、Östergötland County、スウェーデン、58185
        • Linköping University Hospital
        • コンタクト：

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

  • 大人
  • 高齢者

健康ボランティアの受け入れ

いいえ

説明

Inclusion Criteria:

  1. The subject is a postmenopausal woman aged 60 years or older at screening.
  2. The subject has provided written informed consent before any trial-specific procedure is performed.
  3. The subject has osteoporosis at screening defined as a T-score of -2.5 or lower at the total hip or lumbar spine (L1-L4) on central reader confirmed bone densitometry by DXA.
  4. The subject is at high fracture risk, defined by at least one of the following: a previous low-trauma fracture after age 50 years (excluding skull, face, fingers and toes); FRAX probability at or above the age-specific Swedish intervention threshold (using Nordic and Nordic borne calculations, as appropriate) in use at screening.
  5. Corrected plasma calcium or ionized calcium is within the local reference range before randomization.
  6. Serum 25-hydroxyvitamin D concentration ≥50 nmol/L before randomization.
  7. Adequate renal function for zoledronic acid treatment, defined as creatinine clearance ≥35 mL/min calculated using the clinical trial center specified calculation procedure (e.g. the Cockcroft-Gault equation) before randomization.
  8. The subject is able and willing, in the investigator's judgment, to comply with the trial procedures and attend scheduled visits.
  9. For participants entering the extension, separate written extension consent is obtained before any extension-specific procedure is performed.

Exclusion Criteria:

  1. Severe osteoporosis, defined as total hip or lumbar spine T-score < -3.5 and/or prevalent grade 2 or grade 3 vertebral fracture.
  2. Previous myocardial infarction or stroke at any time before screening.
  3. Transient ischemic attack, unstable angina, coronary or major peripheral revascularization within 12 months before screening, decompensated heart failure, uncontrolled clinically relevant arrhythmia, or any cardiovascular condition that in the investigator's judgment confers unacceptably high risk of a major adverse cardiovascular event during study participation.
  4. Use of intravenous bisphosphonate therapy or teriparatide within 3 years before randomization.
  5. Use of oral bisphosphonate or denosumab within 12 months before randomization.
  6. Any previous use of romosozumab.
  7. Use of systemic estrogen, selective estrogen receptor modulator within 3 months.
  8. Use of oral glucocorticoids for more than 14 consecutive days during the 6 months before screening.
  9. Known metabolic bone disease other than postmenopausal osteoporosis, including but not limited to Pagets disease, osteomalacia, untreated hyperparathyroidism, osteogenesis imperfecta, or active renal osteodystrophy.
  10. Creatinine clearance below 35 mL/min, rapidly deteriorating renal function, or another renal condition that makes zoledronic acid unsafe.
  11. Hypocalcaemia (ionized calcium <1.15 mmol/l or total albumin corrected calcium of <2.15 mmol/l) or vitamin D 25-OH-vit-D <50nmol/l, not corrected before randomization.
  12. Unexplained serum alkaline phosphatase >2 times the local upper limit of normal.
  13. Malignancy within the last 5 years, except adequately treated basal-cell carcinoma of the skin, squamous-cell carcinoma in situ of the skin, or cervical carcinoma in situ.
  14. Current osteonecrosis of the jaw, unhealed oral or jaw lesions, active dental or jaw infection, or planned invasive dental extraction/implant procedure that has not been completed and healed before randomization, if considered by the investigator to represent a contraindication or unacceptable risk for treatment with romosozumab, denosumab or zoledronic acid.
  15. Known hypersensitivity or contraindication to romosozumab, denosumab, zoledronic acid, calcium supplementation, or vitamin D supplementation that cannot be safely managed under the protocol.
  16. Inability to undergo protocol DXA/VFA reliably, for example because of body habitus exceeding scanner limits, inability to position safely, or interfering hardware or artefacts that prevent valid endpoint assessment.
  17. Current participation, or recent participation within 30 days or five half-lives (whichever is longer), in another interventional clinical trial that could affect safety or data interpretation.
  18. Any other medical, psychiatric, social or logistical condition that, in the investigators opinion, makes participation unsafe or would compromise protocol adherence or data reliability.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：ランダム化
  • 介入モデル：並列代入
  • マスキング：独身

武器と介入

参加者グループ / アーム
介入・治療
実験的：Short-course Romosozumab Followed by Denosumab
Participants will receive romosozumab 210 mg by subcutaneous injection at Baseline and Months 1 and 2, followed by denosumab 60 mg by subcutaneous injection at Months 3, 9, 15, and 21. Participants entering the optional extension will continue denosumab at Months 27, 33, 39, and 45, unless contraindicated or clinically inappropriate. All participants will receive daily calcium and vitamin D supplementation throughout the study.
薬：Romosozumab
Romosozumab 210 mg will be administered by subcutaneous injection once monthly for 3 consecutive months. Each monthly dose consists of two consecutive 105 mg injections.
他の名前：
  • 均一性
ダイエットサプリメント：Calcium 500 mg and Vitamin D3 800 IU
Calcium and vitamin D supplementation, using 500 mg elemental calcium plus 20 micrograms cholecalciferol daily for 24 months. Participants entering the optional extension will receive daily calcium and vitamin D supplementation throughout the study.
薬：Denosumab
Denosumab 60 mg by subcutaneous injection at Months 3, 9, 15, and 21. Participants entering the optional extension will continue denosumab at Months 27, 33, 39, and 45 unless contraindicated or clinically inappropriate.
アクティブコンパレータ：Zoledronic Acid
Participants will receive zoledronic acid 5 mg by intravenous infusion at Baseline and Month 12. Participants entering the optional extension will receive additional infusions at Months 24 and 36, unless contraindicated or clinically inappropriate. All participants will receive daily calcium and vitamin D supplementation throughout the study.
ダイエットサプリメント：Calcium 500 mg and Vitamin D3 800 IU
Calcium and vitamin D supplementation, using 500 mg elemental calcium plus 20 micrograms cholecalciferol daily for 24 months. Participants entering the optional extension will receive daily calcium and vitamin D supplementation throughout the study.
薬：Zoledronic Acid 5 MG in 5 ML Injection
Zoledronic acid 5 mg intravenously at Baseline and Month 12, with additional doses at Months 24 and 36 in the extension unless contraindicated or clinically inappropriate.

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Percent change in total hip bone mineral density
時間枠：24 months
Percentage change from baseline to month 24 in total hip bone mineral density, measured by dual-energy X-ray absorptiometry.
24 months

二次結果の測定

結果測定
メジャーの説明
時間枠
Percent change in lumbar spine bone mineral density at Months 6, 12 and 24.
時間枠：Baseline to 6, 12 and 24 months.
Percentage change from baseline to months 6, 12 and 24 in lumbar spine bone mineral density, measured by dual-energy X-ray absorptiometry.
Baseline to 6, 12 and 24 months.
Percent Change From Baseline in Total Hip BMD at Months 6 and 12
時間枠：Baseline to 6 and 12 months.
Percentage change from baseline to month 6 and 12 total hip mineral density, measured by dual-energy X-ray absorptiometry.
Baseline to 6 and 12 months.
Incident vertebral fracture
時間枠：From baseline to months 12, 24 in the main study. For those entering the extension study, from baseline to months 36 and 48.
Incident morphometric vertebral fracture by Genant grading on centrally read vertebral fracture assessment (VFA)
From baseline to months 12, 24 in the main study. For those entering the extension study, from baseline to months 36 and 48.
First clinical fragility fracture
時間枠：Baseline to month 24, and for those entering the extension study, to months 36 and 48.
Time to first clinical fragility fracture
Baseline to month 24, and for those entering the extension study, to months 36 and 48.
Occurrence of any fracture during follow-up.
時間枠：Baseline to Month 24, and for those entering the extension study, to Months 36 and 48.
Occurrence of any new morphometric vertebral fracture or clinical fragility fracture during follow-up.
Baseline to Month 24, and for those entering the extension study, to Months 36 and 48.
Percent Change From Baseline in plasma C-Terminal Telopeptide of Type I Collagen
時間枠：Baseline and Months 1, 3, 6, 12, and 24
Percent change from baseline in plasma C-terminal telopeptide of type I collagen (CTX), a marker of bone resorption. Samples will be collected before study-drug administration at treatment visits and analysed centrally. Treatment-group differences over time will be assessed using a longitudinal repeated-measures model.
Baseline and Months 1, 3, 6, 12, and 24
Percent Change From Baseline in Plasma Procollagen Type I N-Terminal Propeptide
時間枠：Baseline and Months 1, 3, 6, 12, and 24
Percent change from baseline in Plasma Procollagen Type I N-Terminal Propeptide, a marker of bone formation. Samples will be collected before study-drug administration at treatment visits and analysed centrally. Treatment-group differences over time will be assessed using a longitudinal repeated-measures model.
Baseline and Months 1, 3, 6, 12, and 24
EuroQol 5-Dimension 5-Level (EQ-5D-5L) Health-State Utility Index
時間枠：Baseline, Month 12, and Month 24
The EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire will be converted to a health-state utility index using the prespecified Swedish value set. Index values range from -0.31 to 1.00, where 1.00 represents full health and higher values indicate better health-related quality of life. Between-group changes from baseline will be evaluated at Months 12 and 24.
Baseline, Month 12, and Month 24
Model-Estimated Lifetime Number of Fractures
時間枠：Month 24
Expected lifetime numbers of hip, vertebral, and other osteoporotic fractures will be estimated for each treatment strategy using a lifetime decision-analytic osteoporosis model informed by the randomized Month-24 total hip BMD treatment difference and Swedish epidemiological data.
Month 24
Budget Impact of the Sequential Treatment Strategy
時間枠：Month 24
Estimated net financial impact over a prespecified 5-year implementation horizon of introducing the sequential treatment strategy in Swedish clinical practice, based on the eligible population, expected uptake, treatment costs, and projected fracture-related cost offsets.
Month 24

その他の成果指標

結果測定
メジャーの説明
時間枠
Model-Predicted Fracture Risk Reduction Based on Total Hip BMD
時間枠：Month 24
Fracture-specific relative and absolute risk reductions will be estimated from the adjusted randomized between-group difference in percent change from baseline in total hip BMD at Month 24. The treatment difference will be translated into expected fracture-risk reductions using prespecified validated meta-regression models underpinning the FDA-qualified total hip BMD surrogate endpoint. Estimates may include hip, vertebral, nonvertebral, and all clinical fractures, according to the available validated models.
Month 24
Incremental Cost per Quality-Adjusted Life-Year (QALY) Gained
時間枠：Month 24
Incremental cost per quality-adjusted life-year gained for the sequential treatment strategy compared with zoledronic acid, estimated from a Swedish healthcare perspective using a lifetime health-economic model. The model will use treatment effects derived from the randomized Month-24 total hip BMD difference together with Swedish epidemiological, cost, mortality, and utility inputs.
Month 24
Model-Estimated Lifetime Healthcare Costs
時間枠：Month 24
Discounted lifetime healthcare costs per participant, including treatment, administration, monitoring, adverse-event management, and fracture-related healthcare costs, estimated from a Swedish healthcare perspective using a lifetime health-economic model based on treatment effects and other study data available at Month 24.
Month 24
Model-Estimated Quality-Adjusted Life-Years
時間枠：Month 24
Discounted lifetime quality-adjusted life-years (QALYs) per participant estimated using EQ-5D-5L and prespecified fracture-state utility inputs in a lifetime health-economic model based on treatment effects and other study data available at Month 24.
Month 24

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Sahlgrenska University Hospital

協力者

Karolinska University Hospital
Göteborg University
Sundsvall Hospital
Region Stockholm
University Hospital, Linkoeping
Skane University Hospital
Uppsala University Hospital
Skaraborg Hospital
Norrlands University Hospital

捜査官

  • 主任研究者：Mattias Lorentzon, MD, PhD、Sahlgrenska University Hospital Mölndal, Västra Götalandsregionen and University of Gothenburg

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (推定)

2027年1月11日

一次修了 (推定)

2029年12月31日

研究の完了 (推定)

2031年12月31日

試験登録日

最初に提出

2026年8月13日

QC基準を満たした最初の提出物

2026年8月18日

最初の投稿 (実際)

2026年8月19日

学習記録の更新

投稿された最後の更新 (実際)

2026年8月19日

QC基準を満たした最後の更新が送信されました

2026年8月18日

最終確認日

2026年8月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • 2026-527447-18-00 (Ctis)

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

はい

IPD プランの説明

De-identified individual participant data underlying the published results may be made available to qualified researchers upon reasonable request. Supporting documents may include the study protocol, statistical analysis plan, and a redacted clinical study report.

IPD 共有時間枠

Beginning after publication of the primary study results and available for a period determined by applicable institutional and data-retention policies.

IPD 共有アクセス基準

De-identified individual participant data and supporting study documents may be made available to qualified researchers upon reasonable request after publication of the primary results, subject to scientific review, applicable ethical and data-protection requirements, and a data-use agreement.

IPD 共有サポート情報タイプ

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

いいえ

米国FDA規制機器製品の研究

いいえ

米国で製造され、米国から輸出された製品。

はい

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

購読する