Trial Outcomes & Findings for The Use of Zoledronic Acid to Prevent Cancer-treatment Bone Loss in Post-menopausal Women Receiving Adjuvant Letrozole for Breast Cancer (NCT NCT00171314)
NCT ID: NCT00171314
Last Updated: 2012-04-11
Results Overview
Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = \[(BMD at Visit - BMD at Baseline) / BMD at Baseline\] \* 100.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
527 participants
Primary outcome timeframe
From Baseline - 12 months
Results posted on
2012-04-11
Participant Flow
Participant milestones
| Measure |
Upfront Zoledronic Acid
Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
|
Delayed Zoledronic Acid
Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score \<= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
|
|---|---|---|
|
Overall Study
STARTED
|
263
|
264
|
|
Overall Study
Safety Population
|
254
|
269
|
|
Overall Study
COMPLETED
|
172
|
186
|
|
Overall Study
NOT COMPLETED
|
91
|
78
|
Reasons for withdrawal
| Measure |
Upfront Zoledronic Acid
Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
|
Delayed Zoledronic Acid
Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score \<= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
|
|---|---|---|
|
Overall Study
Adverse Event
|
44
|
41
|
|
Overall Study
Lack of Efficacy
|
19
|
14
|
|
Overall Study
Withdrawal by Subject
|
9
|
6
|
|
Overall Study
Abnormal Test Procedure Results
|
9
|
3
|
|
Overall Study
Protocol Violation
|
3
|
7
|
|
Overall Study
Administrative Problems
|
4
|
3
|
|
Overall Study
Lost to Follow-up
|
1
|
3
|
|
Overall Study
Death
|
2
|
1
|
Baseline Characteristics
The Use of Zoledronic Acid to Prevent Cancer-treatment Bone Loss in Post-menopausal Women Receiving Adjuvant Letrozole for Breast Cancer
Baseline characteristics by cohort
| Measure |
Upfront Zoledronic Acid
n=263 Participants
Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
|
Delayed Zoledronic Acid
n=264 Participants
Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score \<= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
|
Total
n=527 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
58.2 years
STANDARD_DEVIATION 8.19 • n=5 Participants
|
58.4 years
STANDARD_DEVIATION 7.73 • n=7 Participants
|
58.29 years
STANDARD_DEVIATION 7.96 • n=5 Participants
|
|
Sex: Female, Male
Female
|
263 Participants
n=5 Participants
|
264 Participants
n=7 Participants
|
527 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From Baseline - 12 monthsPopulation: For the analysis of safety, the safety population for treatment arms were defined by the actual treatment received, rather than the treatment arm assigned by randomization. Participants with observations at baseline and 12 months were included in this analysis.
Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = \[(BMD at Visit - BMD at Baseline) / BMD at Baseline\] \* 100.
Outcome measures
| Measure |
Upfront Zoledronic Acid
n=254 Participants
Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
|
Delayed Zoledronic Acid
n=269 Participants
Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score \<= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
|
|---|---|---|
|
Percent Change in Lumbar Spine (L2-L4) BMD After 12 Months of Letrozole Therapy
|
2.680 Percent Change
Standard Deviation 2.8451
|
-3.314 Percent Change
Standard Deviation 3.9632
|
SECONDARY outcome
Timeframe: From Baseline to Year 2, Year 3, Year 4, Year 5Population: Analysis of safety:safety population for treatment arms were defined by the actual treatment received, rather than the treatment arm assigned by randomization. "n" in each category indicates participants with data at baseline and each corresponding timepoint.
Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = \[(BMD at Visit - BMD at Baseline) / BMD at Baseline\] \* 100.
Outcome measures
| Measure |
Upfront Zoledronic Acid
n=254 Participants
Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
|
Delayed Zoledronic Acid
n=269 Participants
Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score \<= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
|
|---|---|---|
|
Percent Change in Lumbar Spine (L2-L4) BMD at 2 Years, 3 Years, 4 Years and 5 Years
Year 2 (n=122,142)
|
4.136 Percent Change
Standard Deviation 3.8182
|
-3.924 Percent Change
Standard Deviation 4.7442
|
|
Percent Change in Lumbar Spine (L2-L4) BMD at 2 Years, 3 Years, 4 Years and 5 Years
Year 3 (n=119,133)
|
4.777 Percent Change
Standard Deviation 4.8959
|
-4.297 Percent Change
Standard Deviation 5.3583
|
|
Percent Change in Lumbar Spine (L2-L4) BMD at 2 Years, 3 Years, 4 Years and 5 Years
Year 4 (n=104, 122)
|
5.462 Percent Change
Standard Deviation 5.2922
|
-4.746 Percent Change
Standard Deviation 5.6588
|
|
Percent Change in Lumbar Spine (L2-L4) BMD at 2 Years, 3 Years, 4 Years and 5 Years
Year 5 (n=86, 102)
|
6.013 Percent Change
Standard Deviation 5.4366
|
-4.572 Percent Change
Standard Deviation 6.1617
|
SECONDARY outcome
Timeframe: From Baseline to Year 1, Year 2, Year 3, Year 4, Year 5Population: For the analysis of safety, the safety population for treatment arms were defined by the actual treatment received, rather than the treatment arm assigned by randomization.
Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = \[(BMD at Visit - BMD at Baseline) / BMD at Baseline\] \* 100.
Outcome measures
| Measure |
Upfront Zoledronic Acid
n=254 Participants
Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
|
Delayed Zoledronic Acid
n=269 Participants
Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score \<= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
|
|---|---|---|
|
Percent Change in Lumbar Spine (L1-L4) BMD at Year 1, Year 2, Year 3, Year 4 and Year 5
Year 1 (n=123, 156)
|
2.330 Percent Change
Standard Deviation 2.7465
|
-3.532 Percent Change
Standard Deviation 3.7830
|
|
Percent Change in Lumbar Spine (L1-L4) BMD at Year 1, Year 2, Year 3, Year 4 and Year 5
Year 2 (n=122, 142)
|
3.994 Percent Change
Standard Deviation 3.6344
|
-3.934 Percent Change
Standard Deviation 4.7162
|
|
Percent Change in Lumbar Spine (L1-L4) BMD at Year 1, Year 2, Year 3, Year 4 and Year 5
Year 3 (n=199, 133)
|
4.523 Percent Change
Standard Deviation 4.5197
|
-4.292 Percent Change
Standard Deviation 5.2317
|
|
Percent Change in Lumbar Spine (L1-L4) BMD at Year 1, Year 2, Year 3, Year 4 and Year 5
Year 4 (n=104, 122)
|
5.051 Percent Change
Standard Deviation 4.9739
|
-4.713 Percent Change
Standard Deviation 5.4101
|
|
Percent Change in Lumbar Spine (L1-L4) BMD at Year 1, Year 2, Year 3, Year 4 and Year 5
Year 5 (n=86, 102)
|
5.476 Percent Change
Standard Deviation 5.0395
|
-4.692 Percent Change
Standard Deviation 6.0242
|
SECONDARY outcome
Timeframe: From baseline to Year 1, Year 2, Year 3, Year 4, Year 5Population: For the analysis of safety, the safety population for treatment arms were defined by the actual treatment received, rather than the treatment arm assigned by randomization. During different time points, participants with observations at that time point were included in the analysis.
Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = \[(BMD at Visit - BMD at Baseline) / BMD at Baseline\] \* 100.
Outcome measures
| Measure |
Upfront Zoledronic Acid
n=254 Participants
Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
|
Delayed Zoledronic Acid
n=269 Participants
Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score \<= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
|
|---|---|---|
|
Percent Change in Total Hip BMD at Year 1, Year 2, Year 3, Year 4 and Year 5
Year 1 (n=173, 187)
|
1.637 Percent Change
Standard Deviation 2.4371
|
-1.644 Percent Change
Standard Deviation 2.9994
|
|
Percent Change in Total Hip BMD at Year 1, Year 2, Year 3, Year 4 and Year 5
Year 2 (n=169, 168)
|
2.119 Percent Change
Standard Deviation 2.9435
|
-2.628 Percent Change
Standard Deviation 3.5659
|
|
Percent Change in Total Hip BMD at Year 1, Year 2, Year 3, Year 4 and Year 5
Year 3 (n=163, 162)
|
1.991 Percent Change
Standard Deviation 3.4207
|
-3.011 Percent Change
Standard Deviation 4.7684
|
|
Percent Change in Total Hip BMD at Year 1, Year 2, Year 3, Year 4 and Year 5
Year 4 (n=145, 152)
|
2.439 Percent Change
Standard Deviation 3.5236
|
-3.074 Percent Change
Standard Deviation 5.4515
|
|
Percent Change in Total Hip BMD at Year 1, Year 2, Year 3, Year 4 and Year 5
Year 5 (n=119, 121)
|
2.788 Percent Change
Standard Deviation 3.8386
|
-4.012 Percent Change
Standard Deviation 5.1321
|
SECONDARY outcome
Timeframe: Year 3Population: For the analysis of safety, the safety population for treatment arms were defined by the actual treatment received, rather than the treatment arm assigned by randomization. Participants with observations at Year 3 were included in this analysis.
Radiological Fracture at 36 months which was not present at baseline = (new fracture/number participant analyzed)\*100. Evaluation of radiological fractures were based on central lab X-ray data. A subject with multiple fractures at the same time or multiple fractures with the same grade is counted only once for that treatment.
Outcome measures
| Measure |
Upfront Zoledronic Acid
n=254 Participants
Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
|
Delayed Zoledronic Acid
n=269 Participants
Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score \<= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
|
|---|---|---|
|
Percentage of Participants With Radiological (Vertebra) Fractures Which Were Not Present at Baseline But Were Present at Year 3
|
2.8 Percentage of Participants
|
3.3 Percentage of Participants
|
Adverse Events
Upfront Zoledronic Acid
Serious events: 47 serious events
Other events: 225 other events
Deaths: 0 deaths
Delayed Zoledronic Acid
Serious events: 56 serious events
Other events: 240 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Upfront Zoledronic Acid
n=254 participants at risk
Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1
|
Delayed Zoledronic Acid
n=269 participants at risk
Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score \<= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.39%
1/254
|
0.37%
1/269
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.39%
1/254
|
0.00%
0/269
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.39%
1/254
|
0.00%
0/269
|
|
Cardiac disorders
Acute myocardial infarction
|
0.39%
1/254
|
0.00%
0/269
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/254
|
1.1%
3/269
|
|
Cardiac disorders
Angina unstable
|
0.00%
0/254
|
0.37%
1/269
|
|
Cardiac disorders
Bundle branch block left
|
0.00%
0/254
|
0.37%
1/269
|
|
Cardiac disorders
Cardiac failure
|
1.6%
4/254
|
0.37%
1/269
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/254
|
0.37%
1/269
|
|
Cardiac disorders
Coronary artery stenosis
|
0.39%
1/254
|
0.00%
0/269
|
|
Cardiac disorders
Cytotoxic cardiomyopathy
|
0.39%
1/254
|
0.00%
0/269
|
|
Cardiac disorders
Mitral valve incompetence
|
0.39%
1/254
|
0.00%
0/269
|
|
Cardiac disorders
Myocardial infarction
|
0.79%
2/254
|
0.00%
0/269
|
|
Cardiac disorders
Myocardial ischaemia
|
0.39%
1/254
|
0.00%
0/269
|
|
Cardiac disorders
Palpitations
|
0.39%
1/254
|
0.00%
0/269
|
|
Cardiac disorders
Pericardial effusion
|
0.39%
1/254
|
0.00%
0/269
|
|
Congenital, familial and genetic disorders
Tracheo-oesophageal fistula
|
0.39%
1/254
|
0.00%
0/269
|
|
Endocrine disorders
Goitre
|
0.39%
1/254
|
0.00%
0/269
|
|
Eye disorders
Cataract
|
0.39%
1/254
|
0.00%
0/269
|
|
Eye disorders
Cataract cortical
|
0.00%
0/254
|
0.37%
1/269
|
|
Eye disorders
Conjunctival hyperaemia
|
0.39%
1/254
|
0.00%
0/269
|
|
Eye disorders
Corneal oedema
|
0.39%
1/254
|
0.00%
0/269
|
|
Gastrointestinal disorders
Abdominal pain
|
0.39%
1/254
|
0.00%
0/269
|
|
Gastrointestinal disorders
Abdominal strangulated hernia
|
0.00%
0/254
|
0.37%
1/269
|
|
Gastrointestinal disorders
Constipation
|
0.39%
1/254
|
0.00%
0/269
|
|
Gastrointestinal disorders
Diverticulum
|
0.00%
0/254
|
0.37%
1/269
|
|
Gastrointestinal disorders
Duodenal ulcer haemorrhage
|
0.00%
0/254
|
0.37%
1/269
|
|
Gastrointestinal disorders
Dyspepsia
|
0.39%
1/254
|
0.00%
0/269
|
|
Gastrointestinal disorders
Gingival erosion
|
0.00%
0/254
|
0.37%
1/269
|
|
Gastrointestinal disorders
Gingivitis
|
0.00%
0/254
|
0.37%
1/269
|
|
Gastrointestinal disorders
Large intestine perforation
|
0.00%
0/254
|
0.37%
1/269
|
|
Gastrointestinal disorders
Loose tooth
|
0.00%
0/254
|
0.37%
1/269
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/254
|
0.37%
1/269
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.39%
1/254
|
0.00%
0/269
|
|
Gastrointestinal disorders
Peritonitis
|
0.39%
1/254
|
0.74%
2/269
|
|
Gastrointestinal disorders
Splenic artery aneurysm
|
0.00%
0/254
|
0.37%
1/269
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/254
|
0.37%
1/269
|
|
General disorders
Chest pain
|
0.39%
1/254
|
0.00%
0/269
|
|
General disorders
Gait disturbance
|
0.00%
0/254
|
0.37%
1/269
|
|
General disorders
General physical health deterioration
|
0.39%
1/254
|
0.00%
0/269
|
|
General disorders
Impaired healing
|
0.00%
0/254
|
0.37%
1/269
|
|
General disorders
Non-cardiac chest pain
|
0.39%
1/254
|
0.00%
0/269
|
|
General disorders
Sudden death
|
0.00%
0/254
|
0.37%
1/269
|
|
Hepatobiliary disorders
Bile duct stone
|
0.39%
1/254
|
0.00%
0/269
|
|
Hepatobiliary disorders
Cholecystitis
|
0.39%
1/254
|
0.00%
0/269
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.39%
1/254
|
0.37%
1/269
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/254
|
0.74%
2/269
|
|
Immune system disorders
Corneal graft rejection
|
0.39%
1/254
|
0.00%
0/269
|
|
Infections and infestations
Abscess jaw
|
0.39%
1/254
|
0.00%
0/269
|
|
Infections and infestations
Acanthamoeba keratitis
|
0.39%
1/254
|
0.00%
0/269
|
|
Infections and infestations
Appendicitis
|
0.39%
1/254
|
0.37%
1/269
|
|
Infections and infestations
Breast cellulitis
|
0.00%
0/254
|
0.74%
2/269
|
|
Infections and infestations
Cellulitis
|
0.00%
0/254
|
0.37%
1/269
|
|
Infections and infestations
Device related infection
|
0.00%
0/254
|
0.37%
1/269
|
|
Infections and infestations
Diverticulitis
|
0.39%
1/254
|
0.74%
2/269
|
|
Infections and infestations
Erysipelas
|
0.39%
1/254
|
0.00%
0/269
|
|
Infections and infestations
Escherichia sepsis
|
0.00%
0/254
|
0.37%
1/269
|
|
Infections and infestations
Escherichia urinary tract infection
|
0.00%
0/254
|
0.37%
1/269
|
|
Infections and infestations
Gastroenteritis
|
0.39%
1/254
|
0.00%
0/269
|
|
Infections and infestations
Influenza
|
0.39%
1/254
|
0.00%
0/269
|
|
Infections and infestations
Lung infection
|
0.00%
0/254
|
0.37%
1/269
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/254
|
0.37%
1/269
|
|
Infections and infestations
Pleural infection
|
0.39%
1/254
|
0.00%
0/269
|
|
Infections and infestations
Soft tissue infection
|
0.00%
0/254
|
0.37%
1/269
|
|
Infections and infestations
Tooth abscess
|
0.39%
1/254
|
0.37%
1/269
|
|
Infections and infestations
Tooth infection
|
0.39%
1/254
|
0.00%
0/269
|
|
Infections and infestations
Tuberculosis
|
0.00%
0/254
|
0.37%
1/269
|
|
Infections and infestations
Urogenital infection bacterial
|
0.39%
1/254
|
0.00%
0/269
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.79%
2/254
|
0.00%
0/269
|
|
Injury, poisoning and procedural complications
Brain contusion
|
0.00%
0/254
|
0.37%
1/269
|
|
Injury, poisoning and procedural complications
Drug toxicity
|
0.00%
0/254
|
0.74%
2/269
|
|
Injury, poisoning and procedural complications
Fall
|
0.79%
2/254
|
1.1%
3/269
|
|
Injury, poisoning and procedural complications
Fracture
|
0.00%
0/254
|
0.37%
1/269
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/254
|
0.74%
2/269
|
|
Injury, poisoning and procedural complications
Intentional overdose
|
0.39%
1/254
|
0.00%
0/269
|
|
Injury, poisoning and procedural complications
Meniscus lesion
|
0.39%
1/254
|
0.00%
0/269
|
|
Injury, poisoning and procedural complications
Muscle rupture
|
0.00%
0/254
|
0.37%
1/269
|
|
Injury, poisoning and procedural complications
Post procedural discomfort
|
0.39%
1/254
|
0.00%
0/269
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.39%
1/254
|
0.00%
0/269
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.39%
1/254
|
0.00%
0/269
|
|
Investigations
Computerised tomogram thorax abnormal
|
0.39%
1/254
|
0.00%
0/269
|
|
Investigations
Weight increased
|
0.00%
0/254
|
0.37%
1/269
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/254
|
0.37%
1/269
|
|
Metabolism and nutrition disorders
Metabolic alkalosis
|
0.00%
0/254
|
0.37%
1/269
|
|
Metabolism and nutrition disorders
Obesity
|
0.00%
0/254
|
0.37%
1/269
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.79%
2/254
|
0.74%
2/269
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/254
|
0.74%
2/269
|
|
Musculoskeletal and connective tissue disorders
Bone fistula
|
0.39%
1/254
|
0.00%
0/269
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/254
|
0.37%
1/269
|
|
Musculoskeletal and connective tissue disorders
Foot deformity
|
0.00%
0/254
|
0.37%
1/269
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.39%
1/254
|
1.1%
3/269
|
|
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis
|
0.39%
1/254
|
0.00%
0/269
|
|
Musculoskeletal and connective tissue disorders
Myositis
|
0.00%
0/254
|
0.37%
1/269
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.79%
2/254
|
1.9%
5/269
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis of jaw
|
1.2%
3/254
|
0.37%
1/269
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
0.39%
1/254
|
0.00%
0/269
|
|
Musculoskeletal and connective tissue disorders
Primary sequestrum
|
0.39%
1/254
|
0.00%
0/269
|
|
Musculoskeletal and connective tissue disorders
Synovial cyst
|
0.00%
0/254
|
0.37%
1/269
|
|
Musculoskeletal and connective tissue disorders
Trigger finger
|
0.39%
1/254
|
0.00%
0/269
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.00%
0/254
|
0.37%
1/269
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign gastric neoplasm
|
0.39%
1/254
|
0.00%
0/269
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.39%
1/254
|
0.00%
0/269
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon adenoma
|
0.39%
1/254
|
0.00%
0/269
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fibroadenoma of breast
|
0.00%
0/254
|
0.37%
1/269
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Laryngeal cancer
|
0.39%
1/254
|
0.00%
0/269
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
|
0.39%
1/254
|
0.00%
0/269
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to spine
|
0.00%
0/254
|
0.37%
1/269
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cancer
|
0.00%
0/254
|
0.37%
1/269
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer
|
0.00%
0/254
|
0.37%
1/269
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.39%
1/254
|
0.00%
0/269
|
|
Nervous system disorders
Amnestic disorder
|
0.00%
0/254
|
0.37%
1/269
|
|
Nervous system disorders
Carpal tunnel syndrome
|
0.39%
1/254
|
0.00%
0/269
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.00%
0/254
|
0.37%
1/269
|
|
Nervous system disorders
Chronic inflammatory demyelinating polyradiculoneuropathy
|
0.00%
0/254
|
0.37%
1/269
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/254
|
0.37%
1/269
|
|
Nervous system disorders
Ischaemic stroke
|
0.39%
1/254
|
0.00%
0/269
|
|
Nervous system disorders
Monoplegia
|
0.00%
0/254
|
0.37%
1/269
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/254
|
0.37%
1/269
|
|
Nervous system disorders
Parkinson's disease
|
0.00%
0/254
|
0.37%
1/269
|
|
Nervous system disorders
Sciatica
|
0.39%
1/254
|
0.74%
2/269
|
|
Psychiatric disorders
Apathy
|
0.00%
0/254
|
0.37%
1/269
|
|
Psychiatric disorders
Depression
|
0.00%
0/254
|
1.1%
3/269
|
|
Psychiatric disorders
Mental disorder
|
0.39%
1/254
|
0.37%
1/269
|
|
Psychiatric disorders
Mutism
|
0.00%
0/254
|
0.37%
1/269
|
|
Psychiatric disorders
Suicide attempt
|
0.39%
1/254
|
0.74%
2/269
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.39%
1/254
|
0.00%
0/269
|
|
Renal and urinary disorders
Renal failure acute
|
0.39%
1/254
|
0.00%
0/269
|
|
Renal and urinary disorders
Stress urinary incontinence
|
0.00%
0/254
|
0.37%
1/269
|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/254
|
0.37%
1/269
|
|
Reproductive system and breast disorders
Cervical dysplasia
|
0.39%
1/254
|
0.00%
0/269
|
|
Reproductive system and breast disorders
Ovarian cyst
|
1.2%
3/254
|
0.37%
1/269
|
|
Reproductive system and breast disorders
Postmenopausal haemorrhage
|
0.39%
1/254
|
0.00%
0/269
|
|
Reproductive system and breast disorders
Uterine prolapse
|
0.00%
0/254
|
0.37%
1/269
|
|
Reproductive system and breast disorders
Vaginal discharge
|
0.00%
0/254
|
0.37%
1/269
|
|
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
|
0.39%
1/254
|
0.00%
0/269
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.00%
0/254
|
0.74%
2/269
|
|
Respiratory, thoracic and mediastinal disorders
Lung infiltration
|
0.00%
0/254
|
0.37%
1/269
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.79%
2/254
|
0.37%
1/269
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary infarction
|
0.00%
0/254
|
0.37%
1/269
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.39%
1/254
|
0.00%
0/269
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.39%
1/254
|
0.00%
0/269
|
|
Respiratory, thoracic and mediastinal disorders
Vocal cord polyp
|
0.39%
1/254
|
0.00%
0/269
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.39%
1/254
|
0.00%
0/269
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.39%
1/254
|
0.00%
0/269
|
|
Vascular disorders
Circulatory collapse
|
0.00%
0/254
|
0.37%
1/269
|
|
Vascular disorders
Lymphoedema
|
0.00%
0/254
|
0.37%
1/269
|
|
Vascular disorders
Vasoconstriction
|
0.00%
0/254
|
0.37%
1/269
|
|
Vascular disorders
Venous insufficiency
|
0.39%
1/254
|
0.00%
0/269
|
Other adverse events
| Measure |
Upfront Zoledronic Acid
n=254 participants at risk
Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1
|
Delayed Zoledronic Acid
n=269 participants at risk
Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score \<= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1.
|
|---|---|---|
|
Gastrointestinal disorders
Constipation
|
7.9%
20/254
|
5.9%
16/269
|
|
Gastrointestinal disorders
Nausea
|
9.4%
24/254
|
7.8%
21/269
|
|
General disorders
Asthenia
|
10.2%
26/254
|
13.4%
36/269
|
|
General disorders
Fatigue
|
18.1%
46/254
|
21.2%
57/269
|
|
General disorders
Influenza like illness
|
7.1%
18/254
|
1.9%
5/269
|
|
General disorders
Oedema peripheral
|
7.9%
20/254
|
9.7%
26/269
|
|
General disorders
Pyrexia
|
8.3%
21/254
|
1.1%
3/269
|
|
Infections and infestations
Bronchitis
|
3.9%
10/254
|
5.9%
16/269
|
|
Infections and infestations
Influenza
|
5.5%
14/254
|
3.3%
9/269
|
|
Infections and infestations
Nasopharyngitis
|
4.7%
12/254
|
5.2%
14/269
|
|
Investigations
Weight increased
|
13.0%
33/254
|
8.6%
23/269
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
9.4%
24/254
|
12.3%
33/269
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
48.4%
123/254
|
50.6%
136/269
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
16.1%
41/254
|
13.4%
36/269
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
10.6%
27/254
|
7.8%
21/269
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
2.8%
7/254
|
5.6%
15/269
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
10.2%
26/254
|
12.6%
34/269
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
3.9%
10/254
|
5.9%
16/269
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
13.0%
33/254
|
13.0%
35/269
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
4.3%
11/254
|
6.7%
18/269
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
10.2%
26/254
|
17.1%
46/269
|
|
Nervous system disorders
Headache
|
9.4%
24/254
|
10.4%
28/269
|
|
Nervous system disorders
Paraesthesia
|
2.8%
7/254
|
5.6%
15/269
|
|
Psychiatric disorders
Anxiety
|
6.7%
17/254
|
8.2%
22/269
|
|
Psychiatric disorders
Depression
|
5.1%
13/254
|
8.9%
24/269
|
|
Psychiatric disorders
Insomnia
|
7.9%
20/254
|
4.1%
11/269
|
|
Reproductive system and breast disorders
Vulvovaginal dryness
|
5.1%
13/254
|
4.1%
11/269
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.9%
15/254
|
6.3%
17/269
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
3.5%
9/254
|
7.8%
21/269
|
|
Vascular disorders
Hot flush
|
26.0%
66/254
|
37.5%
101/269
|
|
Vascular disorders
Hypertension
|
12.6%
32/254
|
9.3%
25/269
|
|
Vascular disorders
Lymphoedema
|
7.9%
20/254
|
7.1%
19/269
|
Additional Information
Novartis Pharmaceuticals
Novartis Pharamaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER