Toxicity Substudy of Evaluation of Subcutaneous Proleukin in a Randomised International Trial (ESPRIT): TOXIL-2 Substudy
Information source: Kirby Institute
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: ondansetron, ibuprofen, paracetamol (Drug); Ondansetron, ibuprofen, paracetamol (Drug); metoclopramide, ibuprofen, paracetamol (Drug); Metoclopramide, codeine phosphate, ibuprofen, paracetamol (Drug)
Phase: Phase 3
Status: Terminated
Sponsored by: Kirby Institute Official(s) and/or principal investigator(s): Sarah L Pett, M.D, Principal Investigator, Affiliation: Kirby Institute, Faculty of Medicine, University of New South Wales, Sydney, Australia
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.
Clinical Details
Official 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
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: percentage of planned rIL-2 taken during the first rIL-2 dosing cycle while participating in this substudy.
Secondary outcome: Patterns of rIL-2 cycling frequency in the six months after randomisation into the substudyPercentage of planned rIL-2 taken during the cycles after the first cycle 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 Number of patients with dose modifications during the cycle due to toxicity 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 Grade 1-4 creatinine and sodium changes during and after rIL-2 dosing; Changes in quality of life during and after rIL-2 Incidence of SAE and AE
Detailed description:
The research is a randomised open-label substudy of ESPRIT. The substudy is exploring
whether the amount of rIL-2 taken during a dosing cycle of rIL-2 can be increased through
controlling the predictable side-effects of rIL-2 better. This is a four arm study with a
factorial design; patients will be randomised to one of four arms. Each arm consists of
different combinations of adjunctive agents. Each patient will receive paracetamol and
ibuprofen prophylactically throughout the cycle, the other adjunctive agents prescribed will
vary according to which arm the patient is randomised to, but the antiemetic used will be
either ondansetron or metoclopramide with or without low dose codeine phosphate as an
additional analgesic agent. The primary end-point is the percentage of planned rIL-2
actually taken during the cycle. Secondary end-points include safety, side-effects of rIL-2
and the adjunctive agents, CD4+ T-cell changes and quality of life measures.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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
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.
Locations and Contacts
FUNCEI, Buenos Aires, Argentina
Hospital General de Agudos JM Ramos Mejia, Buenos Aires C221, Argentina
Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
Hospital Prof. Alejandro Posadas, Buenos Aires, Argentina
Hospital Interzonal de Agudos San Juan de Dios, La Plata, Argentina
Hospital Interzonal General de Agudos Oscar Alende, Mar del Plata, Argentina
Hospital Central, Mendoza, Argentina
CAICI, Rosario, Argentina
Kaplan Medical Center, Rehovot, Israel
St. Vincent's Hospital, Sydney, New South Wales 2010, Australia
AIDS Medical Unit, Brisbane, Queensland 4002, Australia
Cairns Base Hospital, Cairns, Queensland 4870, Australia
Gold Coast Sexual Health Clinic, Gold Coast, Queensland 4220, Australia
Nambour Hospital, Nambour, Queensland 4560, Australia
Carlton Clinic, Melbourne, Victoria 3000, Australia
The Alfred Hospital, Melbourne, Victoria 3000, Australia
Additional Information
National Centre in HIV Epidemiology and Clinical Research Homepage
Starting date: November 2005
Last updated: April 11, 2012
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