Clinical Trial Results:
Bisphosphonate Therapy with Zoledronic acid or Tenofovir Switching to Improve Low Bone Mineral Density in HIV-Infected Adults
Summary
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EudraCT number |
2013-003359-39 |
Trial protocol |
ES |
Global end of trial date |
26 Mar 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Jun 2025
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First version publication date |
29 Jun 2025
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ZEST
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Australian and New Zealand Clinical Trials Registr: ACTRN12612000776808 | ||
Sponsors
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Sponsor organisation name |
Fundació Clínic per a la Recerca Biomèdica
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Sponsor organisation address |
Villarroel, 170, Barcelona, Spain, 08036
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Public contact |
Dr. Joan Albert Arnaiz, CTU (Clinical Trials Department), 34 93 227 57 07, jaarnaiz@clinic.cat
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Scientific contact |
Dr. Esteban Martínez, Fundació Clínic per a la Recerca Biomèdica, 34 93 227 57 07, estebanm@clinic.cat
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
22 May 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Jan 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
26 Mar 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To compare the effects of zoledronic acid 5 mg IV yearly to switching from tenofovir to another antiretroviral drug on lumbar spine BMD (primary endpoint) over 2 years.
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Protection of trial subjects |
Participants were protected through ethics approval, informed consent, strict eligibility criteria, regular safety monitoring, and oversight by an independent Data Safety Monitoring Board.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
24 Jul 2012
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy, Scientific research | ||
Long term follow-up duration |
24 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Australia: 57
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Country: Number of subjects enrolled |
Spain: 28
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Worldwide total number of subjects |
85
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EEA total number of subjects |
28
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
85
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||
Pre-assignment
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Screening details |
Number of subjects assessed for eligibility: 112 Number of subjects excluded prior to assignment: 25 (Reason: Did not meet inclusion/exclusion criteria – 22 subjects, Reason: Declined to participate – 3 subjects). Number of subjects assigned to trial groups: 87 | ||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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TDF Switch | ||||||||||||||||||||||||
Arm description |
Participants discontinued tenofovir disoproxil fumarate (TDF) and switched to another antiretroviral drug (most commonly abacavir or raltegravir), without receiving zoledronic acid. All participants also received calcium and vitamin D supplementation as needed. | ||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||
Investigational medicinal product name |
Tenofovir disoproxil fumarate (TDF) switch strategy
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Investigational medicinal product code |
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Other name |
TDF switch, antirretroviral switch, ARV switch
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants will switch from tenofovir disoproxil fumarate (TDF) to another potent antiretroviral drug, selected by the study physician based on prior treatment history and tolerability.
The switch options include abacavir, raltegravir, or a boosted protease inhibitor.
The selected antiretroviral will be administered orally, at least once daily, for the duration of the study (2 years).
No bisphosphonate will be administered in this arm.
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Arm title
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Zoledronic acid | ||||||||||||||||||||||||
Arm description |
Participants received intravenous zoledronic acid 5 mg at baseline and at month 12, while continuing their tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy. All participants also received calcium and vitamin D supplementation as needed. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Zoledronic acid
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Investigational medicinal product code |
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Other name |
Aclasta
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Dosage: 5 mg of zoledronic acid once a year.
Administered as a single intravenous infusion.
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Baseline characteristics reporting groups
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Reporting group title |
TDF Switch
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Reporting group description |
Participants discontinued tenofovir disoproxil fumarate (TDF) and switched to another antiretroviral drug (most commonly abacavir or raltegravir), without receiving zoledronic acid. All participants also received calcium and vitamin D supplementation as needed. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Zoledronic acid
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Reporting group description |
Participants received intravenous zoledronic acid 5 mg at baseline and at month 12, while continuing their tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy. All participants also received calcium and vitamin D supplementation as needed. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
TDF Switch
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Reporting group description |
Participants discontinued tenofovir disoproxil fumarate (TDF) and switched to another antiretroviral drug (most commonly abacavir or raltegravir), without receiving zoledronic acid. All participants also received calcium and vitamin D supplementation as needed. | ||
Reporting group title |
Zoledronic acid
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Reporting group description |
Participants received intravenous zoledronic acid 5 mg at baseline and at month 12, while continuing their tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy. All participants also received calcium and vitamin D supplementation as needed. |
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End point title |
Change in lumbar spine bone mineral density (BMD) | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
24 months
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Statistical analysis title |
Lumbar spine BMD change at 24 months | ||||||||||||
Comparison groups |
TDF Switch v Zoledronic acid
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Number of subjects included in analysis |
85
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
4.4
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
2.6 | ||||||||||||
upper limit |
6.3 |
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End point title |
Osteoporosis | |||||||||
End point description |
Incidence of osteoporosis (T-score <-2.5 at hip or spine)
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End point type |
Secondary
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End point timeframe |
24 months
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
From the time of signing the informed consent until 30 days after the participant's final study involvement (defined as the last dose of investigational product or the last study visit, whichever occurs later).
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||
Dictionary version |
22.1
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Reporting groups
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Reporting group title |
TDF Switch
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Reporting group description |
Participants discontinued tenofovir disoproxil fumarate (TDF) and switched to another antiretroviral drug (most commonly abacavir or raltegravir), without receiving zoledronic acid. All participants also received calcium and vitamin D supplementation as needed. | |||||||||||||||||||||||||||||||||
Reporting group title |
Zoledronic acid
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Reporting group description |
Participants received intravenous zoledronic acid 5 mg at baseline and at month 12, while continuing their tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy. All participants also received calcium and vitamin D supplementation as needed. | |||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
The population was predominantly male and Caucasian, limiting generalizability. Results reflect 24-month follow-up; longer-term effects remain unknown. | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/29927785 http://www.ncbi.nlm.nih.gov/pubmed/31361922 |