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Trial registered on ANZCTR


Registration number
ACTRN12605000407695
Ethics application status
Approved
Date submitted
8/09/2005
Date registered
14/09/2005
Date last updated
14/09/2005
Type of registration
Retrospectively registered

Titles & IDs
Public title
ESPRIT TOXIL-2 UNSW PSO 6361
Scientific title
An open-label, randomised study comparing the uptake of rIL-2 in HIV-1 infected individuals receiving different combinations of antiemetics and analgesic agents during rIL-2 dosing in ESPRIT: Toxicity substudy of ESPRIT: TOXIL-2 substudy
Universal Trial Number (UTN)
Trial acronym
ESPRIT TOXIL-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
rlL-2 toxicity
 513 0
Interleukin-2 therapy 514 0
HIV 515 0
Condition category
Condition code
Infection 592 592 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This substudy is an open-label, randomised study comparing the uptake of rIL-2 in HIV-1 infected individuals receiving different combinations of antiemetics and analgesic agents during rIL-2 dosing in ESPRIT. The design is a factorial one with 4 arms, all patients will receive regular ibuprofen and paracetamol from days 1-6 of the rIL-2 dosing cycle in addition, patients will be randomised to receive one of two antiemetic combinations i.e. ondansetron or metoclopramide with or without low dose codeine phosphate as an additional analgesic agent. The intervention will occur for 6 days beginning at day 1 of the rIL-2 dosing cycle and finishing one day after the last dose of rIL-2 on day 5. It is protocol mandated that patients must receive a minimum of one dosing cycle of rIL-2 during the 6 months in which they are randomised into this substudy. However, if desired they can receive more than one dosing cycle of rIL-2 during this 6 mth period provided that they are not at the CD4+ T-cell goal for the study, it is medically safe for them to do so and that cycling does not occur more frequently than every 6-11 weeks (as per the ESPRIT protocol).
Intervention code [1] 407 0
Treatment: Drugs
Comparator / control treatment
Control group
Active

Outcomes
Primary outcome [1] 687 0
Percentage of planned rIL-2 taken during the first rIL-2 dosing cycle while participating in this substudy. The information will be transcribed onto a standardised CRF.
Timepoint [1] 687 0
Assessed at day 1 (day 1 of the dosing cycle of rIL-2), day 5 and day 10 by means of adherence assessment and patient diaries.
Secondary outcome [1] 1403 0
Mean amount of rIL-2 taken during the cycle in million international units (MIU).
Timepoint [1] 1403 0
Secondary outcome [2] 1404 0
Number of cycles initiated
Timepoint [2] 1404 0
During the 6 month period.
Secondary outcome [3] 1405 0
Percentage of planned rIL-2 taken during the cycles
Timepoint [3] 1405 0
After the first cycle.
Secondary outcome [4] 1406 0
Mean difference in rIL-2 taken during each cycle in the six-month period following randomisation into this substudy and rIL-2 uptake during the last dosing cycle immediately prior to participation in the substudy.
Timepoint [4] 1406 0
Secondary outcome [5] 1407 0
Mean time between receipt of rIL-2 on this substudy and the last dosing cycle of rIL-2 prior to entry into the substudy.
Timepoint [5] 1407 0
Secondary outcome [6] 1408 0
Number of patients with dose modifications during the cycle due to toxicity.
Timepoint [6] 1408 0
Secondary outcome [7] 1409 0
Percentage of patients completing any cycle initiated.
Timepoint [7] 1409 0
Secondary outcome [8] 1410 0
Number of patients with grade 1-4 GI toxicities.
Timepoint [8] 1410 0
Secondary outcome [9] 1411 0
Number of patients with grade 1-4 constitutional upset (defined as any or all of the following: flu-like illness/fever/myalgia/arthalgia/headache).
Timepoint [9] 1411 0
Secondary outcome [10] 1412 0
Number of patients with grade 1-4 oedema and/or other clinical manifestations of capillary leak syndrome eg pulmonary oedema.
Timepoint [10] 1412 0
Secondary outcome [11] 1413 0
Number of patients with equal to or greater than 10% weight gain during rIL-2 dosing.
Timepoint [11] 1413 0
Secondary outcome [12] 1414 0
Grade 1-4 creatinine changes during and after rIL-2 dosing.
Timepoint [12] 1414 0
Secondary outcome [13] 1415 0
Grade 1-4 serum sodium changes during and after rIL-2 dosing.
Timepoint [13] 1415 0
Secondary outcome [14] 1416 0
Changes in quality of life during and after rIL-2.
Timepoint [14] 1416 0
Secondary outcome [15] 1417 0
Patterns of use of breakthrough adjunctive therapies.
Timepoint [15] 1417 0
Secondary outcome [16] 1418 0
Safety of adjunctive agents as measured by grade 1-4 toxicity attributed to any of the adjunctive agents.
Timepoint [16] 1418 0
Secondary outcome [17] 1419 0
Incidence of serious adverse events (SAEs) (considered rIL-2-related or related to one of the adjunctive agents) and grade 4 clinical events during and within 8 weeks of the rIL-2 dosing cycle - CD4+ T-cell count change.
Timepoint [17] 1419 0
Secondary outcome [18] 1420 0
Number of patients indicating willingness to receive further rIL-2 following first rIL-2 cycle.
Timepoint [18] 1420 0
Secondary outcome [19] 1421 0
The study visits are screening; baseline (day 1 of the rIL-2 dosing cycle), day 5 of the rIL-2 dosing cycle, day 10 of the rIL-2 dosing cycle and day 60 of the rIL-2 dosing cycle.
Timepoint [19] 1421 0
Secondary outcome [20] 1422 0
Assessment on day 1 and day 60 include a brief clinical assessment and quality of life (QoL) survey over the past 4 weeks; QoL surveys over the past 24 hrs are conducted on day 5 and 10 of the rIL-2 dosing cycle. Blood draws for CD4+ T-cells.
Timepoint [20] 1422 0

Eligibility
Key inclusion criteria
Patients participating in ESPRIT and randomised to the rIL-2 arm, who: 1. are not at CD4+ T-cell target for the protocol;2. have not received rIL-2 for >2 months;3. have reported both GI upset and constitutional side-effects as one of the reasons for either dose modifying in prior cycles or unwillingness to receive further rIL-2;4. are considered by the Investigator as medically safe to receive further dosing with rIL-2; 5. are willing to receive further dosing with rIL-2 at the dose specified by the Investigator; 6. are willing to sign informed consent to participate in the substudy.
Minimum age
Not stated
Maximum age
Not stated
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. All exclusions for the receipt of rIL-2 on ESPRIT, 2. Known allergy to non-steroidal anti-inflammatory drugs (NSAIDS), opiates, 5HT-3 (serotonin-3) inhibitors, anti-dopaminergic antiemetics, or any other components of the proposed adjunct regimens.3. Use of other NSAIDS, cyclooxygenase-2 (COX-2) inhibitors, corticosteroids) or opiates analgesics within two weeks of rIL-2 dosing. Use of low dose aspirin as a cardio-protective agent is allowed.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Concealment will be addressed by use of a single computer allocation. Central randomisation will take place by phone/fax. Computer generated randomisation links will be provided by NCHECR. Links will be stratified by planned dose of recombinant interlukin-2 (IL-2), and will be blocked using a factor held at NCHECR.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Sequence generation will be adjusted according to block size. The Coordinating Centre for the study (based at the National Centre in HIV Epidemiology and Clinical Research (NCHECR), UNSW) and all investigators will remain blinded to the actual block sizes used.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Factorial
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/09/2005
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
168
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 646 0
University
Name [1] 646 0
University of New South Wales
Country [1] 646 0
Australia
Primary sponsor type
University
Name
University of New South Wales, Sydney, Australia.
Address
Country
Australia
Secondary sponsor category [1] 542 0
Government body
Name [1] 542 0
Australian Department of Health and Ageing Therapeutic Goods Administration
Address [1] 542 0
Country [1] 542 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 1773 0
St. Vincents Hospital
Ethics committee address [1] 1773 0
Ethics committee country [1] 1773 0
Australia
Date submitted for ethics approval [1] 1773 0
Approval date [1] 1773 0
Ethics approval number [1] 1773 0
Ethics committee name [2] 1774 0
The Alfred Hospital
Ethics committee address [2] 1774 0
Ethics committee country [2] 1774 0
Australia
Date submitted for ethics approval [2] 1774 0
Approval date [2] 1774 0
Ethics approval number [2] 1774 0
Ethics committee name [3] 1775 0
Nambour Hospital
Ethics committee address [3] 1775 0
Ethics committee country [3] 1775 0
Australia
Date submitted for ethics approval [3] 1775 0
Approval date [3] 1775 0
Ethics approval number [3] 1775 0
Ethics committee name [4] 1776 0
AIDS Medical Unit
Ethics committee address [4] 1776 0
Ethics committee country [4] 1776 0
Australia
Date submitted for ethics approval [4] 1776 0
Approval date [4] 1776 0
Ethics approval number [4] 1776 0
Ethics committee name [5] 1777 0
Carton Clinic
Ethics committee address [5] 1777 0
Ethics committee country [5] 1777 0
Australia
Date submitted for ethics approval [5] 1777 0
Approval date [5] 1777 0
Ethics approval number [5] 1777 0
Ethics committee name [6] 1778 0
Gold Coast Sexual health Clinic
Ethics committee address [6] 1778 0
Ethics committee country [6] 1778 0
Australia
Date submitted for ethics approval [6] 1778 0
Approval date [6] 1778 0
Ethics approval number [6] 1778 0
Ethics committee name [7] 1779 0
Cairns Base Hospital
Ethics committee address [7] 1779 0
Ethics committee country [7] 1779 0
Australia
Date submitted for ethics approval [7] 1779 0
Approval date [7] 1779 0
Ethics approval number [7] 1779 0
Ethics committee name [8] 1780 0
Hospital General de Agudos JM Ramos Mejia
Ethics committee address [8] 1780 0
Ethics committee country [8] 1780 0
Argentina
Date submitted for ethics approval [8] 1780 0
Approval date [8] 1780 0
Ethics approval number [8] 1780 0
Ethics committee name [9] 1781 0
Hospital Italiano de Buenos Aires
Ethics committee address [9] 1781 0
Ethics committee country [9] 1781 0
Argentina
Date submitted for ethics approval [9] 1781 0
Approval date [9] 1781 0
Ethics approval number [9] 1781 0
Ethics committee name [10] 1782 0
FUNCEI
Ethics committee address [10] 1782 0
Ethics committee country [10] 1782 0
Argentina
Date submitted for ethics approval [10] 1782 0
Approval date [10] 1782 0
Ethics approval number [10] 1782 0
Ethics committee name [11] 1783 0
Hospital FJ Muniz
Ethics committee address [11] 1783 0
Ethics committee country [11] 1783 0
Argentina
Date submitted for ethics approval [11] 1783 0
Approval date [11] 1783 0
Ethics approval number [11] 1783 0
Ethics committee name [12] 1784 0
Hospital de Clinicas Jose de San Martin,
Ethics committee address [12] 1784 0
Ethics committee country [12] 1784 0
Argentina
Date submitted for ethics approval [12] 1784 0
Approval date [12] 1784 0
Ethics approval number [12] 1784 0
Ethics committee name [13] 1785 0
Hospital General de Agudos Juan A. Fernandez
Ethics committee address [13] 1785 0
Ethics committee country [13] 1785 0
Argentina
Date submitted for ethics approval [13] 1785 0
Approval date [13] 1785 0
Ethics approval number [13] 1785 0
Ethics committee name [14] 1786 0
Hospital Interzonal General de Agudos Oscar Alende
Ethics committee address [14] 1786 0
Ethics committee country [14] 1786 0
Argentina
Date submitted for ethics approval [14] 1786 0
Approval date [14] 1786 0
Ethics approval number [14] 1786 0
Ethics committee name [15] 1787 0
Hospital Prof. Alejandro Posadas
Ethics committee address [15] 1787 0
Ethics committee country [15] 1787 0
Argentina
Date submitted for ethics approval [15] 1787 0
Approval date [15] 1787 0
Ethics approval number [15] 1787 0
Ethics committee name [16] 1788 0
CAICI
Ethics committee address [16] 1788 0
Ethics committee country [16] 1788 0
Argentina
Date submitted for ethics approval [16] 1788 0
Approval date [16] 1788 0
Ethics approval number [16] 1788 0
Ethics committee name [17] 1789 0
Hospital Interzonal de Agudos San Juan de Dios,
Ethics committee address [17] 1789 0
Ethics committee country [17] 1789 0
Argentina
Date submitted for ethics approval [17] 1789 0
Approval date [17] 1789 0
Ethics approval number [17] 1789 0
Ethics committee name [18] 1790 0
Hospital General de Agudos 'Teodoro Alvarez'
Ethics committee address [18] 1790 0
Ethics committee country [18] 1790 0
Argentina
Date submitted for ethics approval [18] 1790 0
Approval date [18] 1790 0
Ethics approval number [18] 1790 0
Ethics committee name [19] 1791 0
Hospital Rawson
Ethics committee address [19] 1791 0
Ethics committee country [19] 1791 0
Argentina
Date submitted for ethics approval [19] 1791 0
Approval date [19] 1791 0
Ethics approval number [19] 1791 0
Ethics committee name [20] 1792 0
Hospital Central
Ethics committee address [20] 1792 0
Ethics committee country [20] 1792 0
Argentina
Date submitted for ethics approval [20] 1792 0
Approval date [20] 1792 0
Ethics approval number [20] 1792 0
Ethics committee name [21] 1793 0
Kaplan Medical Center
Ethics committee address [21] 1793 0
Ethics committee country [21] 1793 0
Israel
Date submitted for ethics approval [21] 1793 0
Approval date [21] 1793 0
Ethics approval number [21] 1793 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 35942 0
Address 35942 0
Country 35942 0
Phone 35942 0
Fax 35942 0
Email 35942 0
Contact person for public queries
Name 9596 0
Dr Sarah Pett M.D
Address 9596 0
The National Centre in HIV Epidemiology and Clinical Research
Level 2
376 Victoria Street
Darlinghurst NSW 2010
Country 9596 0
Australia
Phone 9596 0
+61 2 93850900
Fax 9596 0
+61 2 93850910
Email 9596 0
spett@nchecr.unsw.edu.au
Contact person for scientific queries
Name 524 0
Dr Sarah Pett M.D
Address 524 0
The National Centre in HIV Epidemiology and Clinical Research
Level 2
376 Victoria Street
Darlinghurst NSW 2010
Country 524 0
Australia
Phone 524 0
+61 2 93850900
Fax 524 0
+61 2 93850910
Email 524 0
spett@nchecr.unsw.edu.au

No information has been provided regarding IPD availability


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No Supporting Document Provided



Results publications and other study-related documents

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