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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00147355




Registration number
NCT00147355
Ethics application status
Date submitted
5/09/2005
Date registered
7/09/2005
Date last updated
12/04/2012

Titles & IDs
Public title
Toxicity Substudy of Evaluation of Subcutaneous Proleukin in a Randomised International Trial (ESPRIT): TOXIL-2 Substudy
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
Secondary ID [1] 0 0
ACTR012605000407695
Secondary ID [2] 0 0
ESPRIT TOXIL-2 UNSW PSO 6361
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ondansetron, ibuprofen, paracetamol
Treatment: Drugs - Ondansetron, ibuprofen, paracetamol
Treatment: Drugs - metoclopramide, ibuprofen, paracetamol
Treatment: Drugs - Metoclopramide, codeine phosphate, ibuprofen, paracetamol

Other: A - Ondansetron 4mg bid + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle

Other: B - Ondansetron 4mg bid + codeine phosphate 15mg tds + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle

Other: D - metoclopramide 10mg qds + codeine phosphate 15mg tds + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle

Other: C - metoclopramide 10mg qds + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle


Treatment: Drugs: ondansetron, ibuprofen, paracetamol
ondansetron 4mg bid + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle

Treatment: Drugs: Ondansetron, ibuprofen, paracetamol
Ondansetron 4mg bid + codeine phosphate 15mg tds + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle

Treatment: Drugs: metoclopramide, ibuprofen, paracetamol
metoclopramide 10mg qds + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle

Treatment: Drugs: Metoclopramide, codeine phosphate, ibuprofen, paracetamol
metoclopramide 10mg qds + codeine phosphate 15mg tds + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
percentage of planned rIL-2 taken during the first rIL-2 dosing cycle while participating in this substudy. - we are comparing the percentage of planned rIL-2 taken when randomised to one of the four combinations used as adjunctive therapies to alleviate the known side-effects of rIL-2
Timepoint [1] 0 0
6 months
Secondary outcome [1] 0 0
Patterns of rIL-2 cycling frequency in the six months after randomisation into the substudy - to explore the patterns of rIL-2 and see if the different adjuntive regimens increase tolerability such that more rIL-2 is taken
Timepoint [1] 0 0
6 months
Secondary outcome [2] 0 0
Percentage of planned rIL-2 taken during the cycles after the first cycle - this is to assess whether the adjuncts to which the patient was randomised as part of this substudy impact on better tolerability of cycles of rIL-2 beyond the first
Timepoint [2] 0 0
6 mths
Secondary outcome [3] 0 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 - to see if the adjuncts to which the patient is randomised improve amount of rIL-2 taken compared to the cycle taken prior to enrollment in this substudy
Timepoint [3] 0 0
6 months
Secondary outcome [4] 0 0
Number of patients with dose modifications during the cycle due to toxicity - to assess whether the adjuncts to which they were randomised reduced the amount of rIL-2 dose modification during the rIL-2 cycle
Timepoint [4] 0 0
6 months
Secondary outcome [5] 0 0
Number of patients with grade 1-4 constitutional upset (defined as any or all of the following: flu-like illness/fever/myalgia/arthralgia/headache) and/or GI upset and/or evidence of capillary leak syndromes - to assess the impact of the randomised adjuntive agents on the predictable side-effects of rIL-2
Timepoint [5] 0 0
6 months
Secondary outcome [6] 0 0
Grade 1-4 creatinine and sodium changes during and after rIL-2 dosing; - to assess the impact of the randomised adjuntive agents on the predictable effects of rIL-2 in regards to salt and water homeostasis and renal function
Timepoint [6] 0 0
6 months
Secondary outcome [7] 0 0
Changes in quality of life during and after rIL-2 - to assess whether the use of different adjunctive agents impacted on the tolerability of rIL-2 during the cycle and post as perceived by the patients qOL
Timepoint [7] 0 0
6 months
Secondary outcome [8] 0 0
Incidence of SAE and AE - to assess the incidence of SAE and AEs that are rIL-2 (captured for the main study) and adjunctive agents
Timepoint [8] 0 0
6 months

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
18 Years
Maximum age
No limit
Gender
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 opiate
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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
St. Vincent's Hospital - Sydney
Recruitment hospital [2] 0 0
AIDS Medical Unit - Brisbane
Recruitment hospital [3] 0 0
Cairns Base Hospital - Cairns
Recruitment hospital [4] 0 0
Gold Coast Sexual Health Clinic - Gold Coast
Recruitment hospital [5] 0 0
Nambour Hospital - Nambour
Recruitment hospital [6] 0 0
Carlton Clinic - Melbourne
Recruitment hospital [7] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Sydney
Recruitment postcode(s) [2] 0 0
4002 - Brisbane
Recruitment postcode(s) [3] 0 0
4870 - Cairns
Recruitment postcode(s) [4] 0 0
4220 - Gold Coast
Recruitment postcode(s) [5] 0 0
4560 - Nambour
Recruitment postcode(s) [6] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Buenos Aires
Country [2] 0 0
Argentina
State/province [2] 0 0
La Plata
Country [3] 0 0
Argentina
State/province [3] 0 0
Mar del Plata
Country [4] 0 0
Argentina
State/province [4] 0 0
Mendoza
Country [5] 0 0
Argentina
State/province [5] 0 0
Rosario
Country [6] 0 0
Israel
State/province [6] 0 0
Rehovot

Funding & Sponsors
Primary sponsor type
Other
Name
Kirby Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
The University of New South Wales
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This substudy is an open-label, randomised study comparing the uptake of recombinant
interleukin-2 (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.
Trial website
https://clinicaltrials.gov/show/NCT00147355
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Sarah L Pett, M.D
Address 0 0
Kirby Institute, Faculty of Medicine, University of New South Wales, Sydney, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT00147355