Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   42336   clinical trials with a EudraCT protocol, of which   6971   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2013-003359-39
    Sponsor's Protocol Code Number:ZEST
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-01-16
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2013-003359-39
    A.3Full title of the trial
    Bisphosphonate Therapy with Zoledronic acid or Tenofovir Switching to Improve Low Bone Mineral Density in HIV-Infected Adults
    Tratamiento con ácido zoledrónico vs sustitución de tenofovir para mejorar la densidad mineral baja en pacientes adultos infectados por el VIH
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Treatment with Zoledronic acid or Tenofovir Switching in HIV-Infected
    Tratamiento con ácido zoledrónico vs sustitución de tenofovir en pacientes infectados por el VIH
    A.4.1Sponsor's protocol code numberZEST
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorFundació Clínic per a la Recerca Biomèdica
    B.1.3.4CountrySpain
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportSt. Vicent's Hospital
    B.4.2CountryAustralia
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCTU (Clinical Trials Unit)
    B.5.2Functional name of contact pointJoan Albert Arnaiz
    B.5.3 Address:
    B.5.3.1Street AddressVillarroel, 170
    B.5.3.2Town/ cityBarcelona
    B.5.3.3Post code08036
    B.5.3.4CountrySpain
    B.5.4Telephone number34932279838
    B.5.5Fax number34932279877
    B.5.6E-mailjaarnaiz@clinic.ub.es
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Aclasta
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Europharm Limited
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Solution for injection/infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNZOLEDRONIC ACID
    D.3.9.1CAS number 118072-93-8
    D.3.9.4EV Substance CodeSUB00176MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    low bone mineral density - HIV
    Baja densidad mineral ósea - VIH
    E.1.1.1Medical condition in easily understood language
    low bone mineral density - HIV
    Baja densidad mineral ósea - VIH
    E.1.1.2Therapeutic area Diseases [C] - Virus Diseases [C02]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 16.1
    E.1.2Level LLT
    E.1.2Classification code 10068341
    E.1.2Term HIV-1 infection
    E.1.2System Organ Class 100000004862
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main 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.
    Comparar el efecto de ácido zolendrónico o la sustitución de tenofovir sobre la densidad mineral ósea lumbar (DMO) a los 2 años.
    E.2.2Secondary objectives of the trial
    To compare the randomised groups for:

    1. other bone parameters
    - mean percent change in hip BMD
    - incidence of osteoporosis (T-score <-2.5 at hip or spine) and of normal BMD (T-score >-1 at hip and spine)
    - fracture risk estimated with the Australian version of the FRAX equation48
    - serum levels of CTx and P1NP
    - fractures (except of the skull, and of the small bones of the hands and feet)

    2. safety (clinical adverse events [all grades]; all serious adverse events; AIDS; death; use of concomitant medications for toxicity; estimated glomerular filtration rate (eGFR, by MDRD equation; laboratory adverse events; virological failure (FDA definition: plasma HIV RNA >400 copies/mL on 2 consecutive occasions ?4 weeks apart)
    3. modifications to ART (after baseline)
    Comparar los efectos de ácido zolendrónico o sustitución de tenofovir sobre:

    1. Otros parámetros óseos:
    - Cambio en la DMO femoral
    - Incidencia de osteoporosis (T-score <-2.5 en columna o fémur) y de DMO normal (T-score >-1 en columna o fémur)
    - Riesgo de fractura estimado con la ecuación FRAX
    - Niveles plasmáticos de telopéptido C terminal (CTx) y del propéptido amino-terminal del procolágeno tipo 1 (P1NP)
    - Fracturas (excepto cráneo y huesos pequeños de manos y pies)
    2. Parámetros de seguridad (acontecimientos adversos clínicos y de laboratorio, acontecimientos adversos graves, SIDA, muerte, uso de medicaciones concomitantes por toxicidad, tasa de filtrado glomerular estimado, y fracaso virológico)
    3. Cambios en el tratamiento antirretroviral
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. provision of written, informed consent
    2. HIV infected adult ?18 years of age
    3. stable and well-tolerated ART including tenofovir for the preceding 6 months
    4. plasma HIV RNA <50 copies/ml for at least the preceding 3 months
    5. eGFR >60ml/min (patients at higher risk of zoledronic acid/tenofovir nephrotoxicity)
    6. spine or neck of femur T score ? -1.0 measured by DXA (i.e. osteopenia)
    1. Otorgar consentimiento informado por escrito
    2. Pacientes adultos VIH positivos (?18 años)
    3. En combinación estable y bien tolerada de tratamiento antirretroviral que incluya tenofovir durante los últimos 6 meses
    4. VIH RNA <50 copias/mL en los últimos 3 meses
    5. Tasa de filtrado glomerular estimada >60 mL/min
    6. T-score (DEXA) de columna o cuello de fémur ?-1.0
    E.4Principal exclusion criteria
    1. prior bisphosphonate therapy
    2. use of tenofovir for previously active chronic hepatitis B co-infection
    3. requiring therapy for low BMD (e.g. prior fragility fracture; other metabolic bone disease)
    4. other secondary causes of osteoporosis: hypogonadism (total testosterone/oestrogen <lower limit of normal and luteinizing hormone >25% above upper normal limit); hypothyroidism (low T4 and elevated TSH); hyperparathyroidism (elevated parathyroid hormone); inhaled fluticasone in a patient receiving ritonavir; prednisolone ?7.5mg/d or equivalent
    5. contra-indications to zoledronic acid (known hypersensitivity to bisphosphonates, hypocalcaemia, prior or current uveitis, eGFR<35 mL/min)
    6. recent (within the last 2 months) or planned dental surgery (at investigators discretion)
    7. previous virological failure (defined above), genotypic resistance, intolerance or contraindication to proposed switch antiretroviral drug
    8. HLA-B*5701 positive (abacavir contra-indicated) or prior ischaemic cardiovascular disease if planning to switch from tenofovir to abacavir
    9. concurrent use of any nephrotoxic drug
    10. breast-feeding or pregnancy
    1. Tratamiento previo con bifosfonatos
    2. Uso de tenofovir para co-infección por hepatitis B crónica
    3. Necesidad de tratamiento por DMO baja (por ejemplo, fractura por fragilidad previa o enfermedad metabólica ósea)
    4. Otras causas de osteoporosis secundaria:
    - Hipogonadismo (testosterona o estrógenos totales bajos y hormona luteinizante >25% por encima del límite normal)
    - Hipotiroidismo (T4 baja y TSH elevada)
    - Hiperparatiroidismo (PTH elevada)
    - Fluticasona inhalada en un paciente que reciba ritonavir
    - Prednisolona ?7.5mg/d o equivalente
    5. Contraindicación para el uso de ácido zolendrónico:
    - Hipersensibilidad conocida a bifosfonatos
    - Hipocalcemia
    - Uveítis previa o actual
    - Tasa de filtrado glomerular estimado <35 mL/min
    6. Cirugía dental reciente (previos 2 meses) o planeada
    7. Fracaso virológico previo, resistencia genotípica, intolerancia o contraindicación para el cambio antirretroviral
    8. Abacavir estará específicamente contraindicado como sustituto de tenofovir en caso de HLA-B*5701 positivo o presentar historia previa de evento cardiovascular isquémico
    9. Uso concomitante de cualquier fármaco nefrotóxico
    10. Lactancia o embarazo
    E.5 End points
    E.5.1Primary end point(s)
    mean percent change at the lumbar spine at 2 yeras
    cambio porcentual medio en densidad mineral ósea lumbar (DMO) a los 2 años
    E.5.1.1Timepoint(s) of evaluation of this end point
    2 years
    2 años
    E.5.2Secondary end point(s)
    - mean percent change in hip BMD
    - incidence of osteoporosis (T-score <-2.5 at hip or spine) and of normal BMD (T-score >-1 at hip and spine)
    - fracture risk estimated with the Australian version of the FRAX equation48
    - serum levels of CTx and P1NP
    - fractures (except of the skull, and of the small bones of the hands and feet)

    2. safety (clinical adverse events [all grades]; all serious adverse events; AIDS; death; use of concomitant medications for toxicity; estimated glomerular filtration rate (eGFR, by MDRD equation; laboratory adverse events; virological failure (FDA definition: plasma HIV RNA >400 copies/mL on 2 consecutive occasions ?4 weeks apart)
    3. modifications to ART (after baseline)
    1.
    - Cambio porcentual medio en la DMO femoral
    - Incidencia de osteoporosis (T-score <-2.5 en columna o fémur) y de DMO normal (T-score >-1 en columna o fémur)
    - Riesgo de fractura estimado con la ecuación FRAX
    - Niveles plasmáticos de telopéptido C terminal (CTx) y del propéptido amino-terminal del procolágeno tipo 1 (P1NP)
    - Fracturas (excepto cráneo y huesos pequeños de manos y pies)
    2. Parámetros de seguridad (acontecimientos adversos clínicos y de laboratorio, acontecimientos adversos graves, SIDA, muerte, uso de medicaciones concomitantes por toxicidad, tasa de filtrado glomerular estimado, y fracaso virológico)
    3. Cambios en el tratamiento antirretroviral
    E.5.2.1Timepoint(s) of evaluation of this end point
    2 years
    2 años
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) Yes
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    last visit of the last subject
    última visita del último paciente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 84
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 84
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state28
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 28
    F.4.2.2In the whole clinical trial 84
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    normal treatment for that condition
    práctica habitual para la condición en estudio
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2014-01-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-10-31
    P. End of Trial
    P.End of Trial StatusCompleted
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA