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

18 августа 2026 г. обновлено: 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.

Обзор исследования

Статус

Еще не набирают

Условия

Вмешательство/лечение

Тип исследования

Интервенционный

Регистрация (Оцененный)

216

Фаза

  • Фаза 4

Контакты и местонахождение

В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.

Контакты исследования

Учебное резервное копирование контактов

  • Имя: Lena Silberberg, BSc
  • Номер телефона: +46313421000
  • Электронная почта: lena.silberberg@vgregion.se

Места учебы

  • Швеция
    • Skåne County
      • Malmö, Skåne County, Швеция, 20502
        • Skåne Universitetssjukhus
        • Контакт:
          • Kristina Åkesson, MD, PhD
          • Номер телефона: +46 40 33 10 00
          • Электронная почта: kristina.akesson@med.lu.se
    • Stockholm County
      • Huddinge, Stockholm County, Швеция, 14186
        • Karolinska University Hospital Huddinge
        • Контакт:
          • Bo Freyschuss, MD, PhD
          • Номер телефона: +46 8123 800 00
          • Электронная почта: bofreyschuss@outlook.com
      • Stockholm, Stockholm County, Швеция, 11361
    • Uppsala County
      • Uppsala, Uppsala County, Швеция, 751 85
        • Akademiska Sjukhuset
        • Контакт:
    • Västerbotten County
      • Umeå, Västerbotten County, Швеция, 90185
        • Norrlands universitetssjukhus
        • Контакт:
    • Västernorrland County
      • Sundsvall, Västernorrland County, Швеция, 856 43
        • Sundsvalls sjukhus
        • Контакт:
    • Västra Götaland County
      • Mölndal, Västra Götaland County, Швеция, 43180
        • Sahlgrenska University Hospital Mölndal
        • Контакт:
      • Skövde, Västra Götaland County, Швеция, 54949
        • Skaraborgs Sjukhus
        • Контакт:
    • Östergötland County
      • Linköping, Östergötland County, Швеция, 58185
        • Linköping University Hospital
        • Контакт:
          • Anna Spångeus, MD, PhD
          • Номер телефона: +46 10 103 00 00
          • Электронная почта: anna.spangeus@liu.se

Критерии участия

Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.

Критерии приемлемости

Возраст, подходящий для обучения

  • Взрослый
  • Пожилой взрослый

Принимает здоровых добровольцев

Нет

Описание

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.

Учебный план

В этом разделе представлена ​​подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.

Как устроено исследование?

Детали дизайна

  • Основная цель: Уход
  • Распределение: Рандомизированный
  • Интервенционная модель: Параллельное назначение
  • Маскировка: Одинокий

Оружие и интервенции

Группа участников / Армия
Вмешательство/лечение
Экспериментальный: 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.
Лекарство: 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.
Другие имена:
  • Равномерность
Диетическая добавка: 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.
Лекарство: 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.
Активный компаратор: 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.
Диетическая добавка: 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.
Лекарство: 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.

Что измеряет исследование?

Первичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Percent change in total hip bone mineral density
Временное ограничение: 24 months
Percentage change from baseline to month 24 in total hip bone mineral density, measured by dual-energy X-ray absorptiometry.
24 months

Вторичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Percent change in lumbar spine bone mineral density at Months 6, 12 and 24.
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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.
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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

Другие показатели результатов

Мера результата
Мера Описание
Временное ограничение
Model-Predicted Fracture Risk Reduction Based on Total Hip BMD
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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

Соавторы и исследователи

Здесь вы найдете людей и организации, участвующие в этом исследовании.

Спонсор

Sahlgrenska University Hospital

Соавторы

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

Следователи

  • Главный следователь: Mattias Lorentzon, MD, PhD, Sahlgrenska University Hospital Mölndal, Västra Götalandsregionen and University of Gothenburg

Даты записи исследования

Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.

Изучение основных дат

Начало исследования (Оцененный)

11 января 2027 г.

Первичное завершение (Оцененный)

31 декабря 2029 г.

Завершение исследования (Оцененный)

31 декабря 2031 г.

Даты регистрации исследования

Первый отправленный

13 августа 2026 г.

Впервые представлено, что соответствует критериям контроля качества

18 августа 2026 г.

Первый опубликованный (Действительный)

19 августа 2026 г.

Обновления учебных записей

Последнее опубликованное обновление (Действительный)

19 августа 2026 г.

Последнее отправленное обновление, отвечающее критериям контроля качества

18 августа 2026 г.

Последняя проверка

1 августа 2026 г.

Дополнительная информация

Термины, связанные с этим исследованием

Ключевые слова

Дополнительные соответствующие термины MeSH

Другие идентификационные номера исследования

  • 2026-527447-18-00 (Ктис)

Планирование данных отдельных участников (IPD)

Планируете делиться данными об отдельных участниках (IPD)?

ДА

Описание плана IPD

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.

Сроки обмена IPD

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

Критерии совместного доступа к IPD

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.

Совместное использование IPD Поддерживающий тип информации

  • STUDY_PROTOCOL
  • САП
  • МКФ
  • АНАЛИТИЧЕСКИЙ_КОД
  • КСО

Информация о лекарствах и устройствах, исследовательские документы

Изучает лекарственный продукт, регулируемый FDA США.

Нет

Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.

Нет

продукт, произведенный в США и экспортированный из США.

Да

Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .

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