Ignite Creation Date:
2025-12-25 @ 12:59 AM
Ignite Modification Date:
2025-12-27 @ 12:48 PM
Study NCT ID:
NCT05025293
Status:
RECRUITING
Last Update Posted:
2024-04-02
First Post:
2021-08-18
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Zoledronate Early to Hip Fracture Patients - Safe and Effective?
Sponsor:
Lene Bergendal Solberg
Organization:
Study Overview
Official Title:
Zoledronate Early to Hip Fracture Patients - Safe and Effective? A Double-blinded Randomized Controlled Treatment Strategy Trial on Zoledronate in Hip Fracture Patients
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ZEBRA
Brief Summary:
To prevent hip fracture patients for having another fracture, secondary fracture preventing medication should be given as soon as possible. Zoledronate is the most efficient bisphosphonate and is given as an intravenous infusion once yearly. However, the appropriate time to initiate zoledronate treatment after a hip fracture has not yet been established. To clarify the optimal timing of zoledronate to hip fracture patients we have designed a double-blinded, placebo-controlled randomized non-inferiority trial to compare if zoledronate administered early (within 5 days) after hip fracture surgery is as good as zoledronate given late (3 months) after hip fracture surgery.
Detailed Description:
Hip fracture patients have the highest risk for recurrent hip or other osteoporotic fractures. We have efficient fracture preventing medication easily available, but few patients receive them. We therefore need to create simple systems to ensure that these frail patients with the highest risk for a new fracture are offered proper treatment early and any delay in treatment should be avoided. Zoledronate is the most efficient bisphosphonate and the drug of choice for hip fracture patients due to the results from the Horizon recurrent fracture trial. It is given as an intravenous infusion once yearly. However, the appropriate time to initiate zoledronate treatment after a hip fracture has not yet been established. The summary of product characteristics (SmPC) for Aclasta (zoledronate) in Norway says that Aclasta should not be administered within the first 2 weeks after the hip fracture, however there have been a practice over years in Norway to give zoledronate to the hip fracture patients during their stay in hospital for fracture treatment. There are logistical and practical advantages of giving zoledronate while the patient is still in hospital for her fracture. It has, however, been questioned whether the effect of zoledronate given within the first 2 weeks postoperatively really is fracture preventing. The results from the post hoc analysis from the Horizon recurrent fracture trial by Eriksen and co-workers in 2009, suggested that given zoledronate within 2-weeks after hip fracture surgery may be a little less fracture preventing. The results from this analysis can be due to the low number of study subjects as well as frailty in the study population causing the large variations. On the other hand, the lack of effect in the within 2-week group may be due to the affinity for zoledronate to bone mineral and the accumulation of zoledronate in the fracture callus during bone repair with less being incorporated in the rest of the skeleton.
To clarify the optimal timing of zoledronate to hip fracture patients we wanted to compare if zoledronate administered early (within 5 days) after hip fracture surgery, while the patients is still in hospital, is as good as zoledronate given late (3 months) after hip fracture surgery.
To test our hypothesis we designed a non-inferiority randomized trial using the bone turnover marker N-terminal propeptide of type I procollagen (P1NP) as the primary endpoint. PINP has in recent years been widely used as a marker to follow the effect of anti-resorptive therapy as it is more robust than the other well studied bone marker; cross-linked C-telopeptide of type I collagen (CTX). P1NP and CTX are recommended as reference markers for bone turnover by the International Osteoporosis Foundation (IOF). Anti-resorptive agents as bisphosphonates influence bone remodeling by decreasing bone resorption (amino-bisphosphonates kills osteoclasts) and thereby also reducing bone formation. This affects the bone turnover markers: Both P1NP and CTX drops in value in a consistent manner reflecting the level of bone suppression and has shown to correlate with the level of bone mineral density and the subsequent fracture risk. P1NP and CTX are therefore well suited to monitor the effect of anti-resorptive therapy as they reflect the bone turnover status in the entire skeleton. It is likely to believe that if zoledronate given early after fracture is accumulated in the fracture callus and too little is incorporated in the entire skeleton, the result will be just a local decrease in bone resorption (only in the fracture callus). This will not to the same extent as a decrease in bone resorption from the entire skeleton, be reflected by the bone turnover markers P1NP and CTX and the fall in these markers will be less than if we give zoledronate after the fracture has healed (after 6-12 weeks).
Eligible patients that meets the study requirements and with an informed consent will be stratified on type of operation (arthroplasty versus internal fixation) and on hospital before randomization 1:1 to either zoledronate early (ZOLearly: zoledronate given within 5 days after hip fracture surgery) or zoledronate late (ZOLlate: zoledronate given 3 months after hip fracture surgery). The patients will be followed for 15 months with study visits at 3 months post fracture and at 6 and 12 months post treatment with zoledronate. The study is double-blinded the first 3 months to be able to test for the "soft" secondary endpoints; delirium and rehabilitation. Approximately 300 patients will be recruited. Estimated recruitment time is 2 years.
To clarify the optimal timing of zoledronate to hip fracture patients we wanted to compare if zoledronate administered early (within 5 days) after hip fracture surgery, while the patients is still in hospital, is as good as zoledronate given late (3 months) after hip fracture surgery.
To test our hypothesis we designed a non-inferiority randomized trial using the bone turnover marker N-terminal propeptide of type I procollagen (P1NP) as the primary endpoint. PINP has in recent years been widely used as a marker to follow the effect of anti-resorptive therapy as it is more robust than the other well studied bone marker; cross-linked C-telopeptide of type I collagen (CTX). P1NP and CTX are recommended as reference markers for bone turnover by the International Osteoporosis Foundation (IOF). Anti-resorptive agents as bisphosphonates influence bone remodeling by decreasing bone resorption (amino-bisphosphonates kills osteoclasts) and thereby also reducing bone formation. This affects the bone turnover markers: Both P1NP and CTX drops in value in a consistent manner reflecting the level of bone suppression and has shown to correlate with the level of bone mineral density and the subsequent fracture risk. P1NP and CTX are therefore well suited to monitor the effect of anti-resorptive therapy as they reflect the bone turnover status in the entire skeleton. It is likely to believe that if zoledronate given early after fracture is accumulated in the fracture callus and too little is incorporated in the entire skeleton, the result will be just a local decrease in bone resorption (only in the fracture callus). This will not to the same extent as a decrease in bone resorption from the entire skeleton, be reflected by the bone turnover markers P1NP and CTX and the fall in these markers will be less than if we give zoledronate after the fracture has healed (after 6-12 weeks).
Eligible patients that meets the study requirements and with an informed consent will be stratified on type of operation (arthroplasty versus internal fixation) and on hospital before randomization 1:1 to either zoledronate early (ZOLearly: zoledronate given within 5 days after hip fracture surgery) or zoledronate late (ZOLlate: zoledronate given 3 months after hip fracture surgery). The patients will be followed for 15 months with study visits at 3 months post fracture and at 6 and 12 months post treatment with zoledronate. The study is double-blinded the first 3 months to be able to test for the "soft" secondary endpoints; delirium and rehabilitation. Approximately 300 patients will be recruited. Estimated recruitment time is 2 years.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 2020-000638-17 | EUDRACT_NUMBER | None | View |