OsteoporosisNCT04736693
Replication of the HORIZON Pivotal Fracture Trial in Healthcare Claims Data
An observational study of Osteoporosis, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
Investigators are building an empirical evidence base for real world data through large-scale replication of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies. Read more about this study
- Who is it for?
- Ages 65 years and older, women only
- Conditions the study is for
- Osteoporosis
- What is being tested?
- Raloxifene and Zoledronic Acid
- How many people
- 18,028 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Sep 2020to 18 Feb 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- Women only
- No healthy volunteers
- Older adult
Study population: This study will involve a new user, parallel group, propensity score-matched, retrospective cohort study design comparing 15-minute annual infusions of zoledronic acid (5mg) to raloxifene. The patients will be required to have continuous enrollment during a baseline period of 450 days (15 months) before initiation of zoledronic acid or comparator. We will restrict the analyses to women, older than 65, with osteoporosis.
Who may be able to join
- Postmenopausal women between the ages of 65 and 89 years
- Osteoporosis diagnosis
Who cannot join
- Bisphosphonate users
- Previous use of:
- Any use of parathyroid hormone
- Use of anabolic steroids or growth hormone within 6 months before cohort entry date OR
- Use of oral or intravenous systemic corticosteroids within 12 months of cohort entry date
- Serious disease that may limit life expectancy to less than 6 months
Show all 20Show fewer
- Malignant neoplasm diagnosis within 12 months prior to the cohort entry date
- Conditions that influence bone metabolism
- Treatment and Prevention of Glucocorticoid-Induced Osteoporosis
- Treatment of Paget's Disease of Bone
- Alcohol abuse/dependence OR Drug abuse/dependence OR Non-compliance
- Pregnancy
- Diagnosis and procedure for amputee of lower limb
- Use of Zoledronic acid within 450 days prior to the cohort entry date
- Use of Denosumab within 450 days prior to the cohort entry date
- Diagnosis of End-Stage Renal Disease OR Diagnosis and procedure for Kidney transplant
- Diagnosis of End-Stage Liver Disease: Cirrhosis, Hepatic decompensation
- Blindness or compromised vision
- Use of Abaloparatide within 450 days prior to the cohort entry date
- Use of Romosozumab within 450 days prior to the cohort entry date
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham And Women's Hospital
Boston, Massachusetts, 02120
About this study
Investigators are building an empirical evidence base for real world data through large-scale replication of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.
Read the detailed description
This is a non-randomized, non-interventional study that is part of the RCT DUPLICATE initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to replicate, as closely as is possible in healthcare insurance claims data, the trial listed below/above. Although many features of the trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not replicable in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for replication for a range of possible reasons and does not provide information on the validity of the original RCT finding.
- Conditions
- Osteoporosis
- Being tested
- Raloxifene, Zoledronic Acid
- Medical subject headings
- Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RaloxifeneDrug
Raloxifene dispensing claim is used as the reference group.
Zoledronic AcidDrug
Zoledronic Acid dispensing claim is used as the exposure group.
| Study group | Role | What they receive |
|---|---|---|
| Raloxifene | Reference Group Receives: Drug: Raloxifene | |
| Zoledronic Acid | Exposure Group Receives: Drug: Zoledronic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with hip fracture
Please refer to attached protocol for full definition due to size limitations
Measured: Through study completion (earliest of 540 days or censoring)
Secondary outcomes (1)
Number of patients with non-vertebral fracture
Please refer to attached protocol for full definition due to size limitations
Measured: Through study completion (earliest of 540 days or censoring)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2021
- Study start22 Sep 2020
- Primary completion18 Feb 2021
- Study completion18 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for OsteoporosisStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 18,028 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shirley Vichy Wang, Brigham and Women's Hospital
- Investigators
- Shirley Wang, PhD, ScM, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04736693
- Sponsor's protocol ID
- 2018P002966-DUP-HORIZON-PFT
- Status last verified
- Jul 2023
- First submitted
- 25 Jan 2021
- Last updated
- 27 Jul 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
D'Andrea E, Schneeweiss S, Franklin JM, Kim SC, Glynn RJ, Lee SB, Wang SV. Efficacy Versus Effectiveness: The HORIZON-Pivotal Fracture Trial and Its Emulation in Claims Data. Arthritis Rheumatol. 2025 Jan;77(1):12-21. doi: 10.1002/art.42968. Epub 2024 Sep 18.
PubMed 39129266
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Replication of the HORIZON Pivotal Fracture Trial in Healthcare Claims Data
- ClinicalTrials.gov ID
- NCT04736693
- Acronym / sponsor ID
- 2018P002966-DUP-HORIZON-PFT
- Conditions
- Osteoporosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 18,028 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 22 Sep 2020 (actual)
- Primary completion
- 18 Feb 2021 (actual)
- Study completion
- 18 Feb 2021 (actual)
- First posted
- 3 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Investigators are building an empirical evidence base for real world data through large-scale replication of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.
Detailed description
This is a non-randomized, non-interventional study that is part of the RCT DUPLICATE initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to replicate, as closely as is possible in healthcare insurance claims data, the trial listed below/above. Although many features of the trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not replicable in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for replication for a range of possible reasons and does not provide information on the validity of the original RCT finding.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Raloxifene | – | Drug: RaloxifeneReference Group |
| Zoledronic Acid | – | Drug: Zoledronic AcidExposure Group |
Who may qualify
- Ages
- 65 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
- Study population
- This study will involve a new user, parallel group, propensity score-matched, retrospective cohort study design comparing 15-minute annual infusions of zoledronic acid (5mg) to raloxifene. The patients will be required to have continuous enrollment during a baseline period of 450 days (15 months) before initiation of zoledronic acid or comparator. We will restrict the analyses to women, older than 65, with osteoporosis.
Key inclusion criteria (2 listed)
- Postmenopausal women between the ages of 65 and 89 years
- Osteoporosis diagnosis
Key exclusion criteria (20 listed)
- Bisphosphonate users
- Previous use of:
- Serious disease that may limit life expectancy to less than 6 months
- Malignant neoplasm diagnosis within 12 months prior to the cohort entry date
- Conditions that influence bone metabolism
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RaloxifeneRaloxifene dispensing claim is used as the reference group. | Drug | Raloxifene |
| Zoledronic AcidZoledronic Acid dispensing claim is used as the exposure group. | Drug | Zoledronic Acid |
Primary outcome
Number of patients with hip fracture
Time frame: Through study completion (earliest of 540 days or censoring)
Please refer to attached protocol for full definition due to size limitations
1 secondary outcome
Number of patients with non-vertebral fracture
Time frame: Through study completion (earliest of 540 days or censoring)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2023.
- Derived from this study: PubMed 39129266D'Andrea E, Schneeweiss S, Franklin JM, Kim SC, Glynn RJ, Lee SB, Wang SV. Efficacy Versus Effectiveness: The HORIZON-Pivotal Fracture Trial and Its Emulation in Claims Data. Arthritis Rheumatol. 2025 Jan;77(1):12-21. doi: 10.1002/art.42968. Epub 2024 Sep 18.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shirley Wang, PhD, ScM principal investigator
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Osteoporosis, run by Brigham and Women's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with hip fracture (time frame: Through study completion (earliest of 540 days or censoring)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04736693, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2023.