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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


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 substudy

Percentage 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.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


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

Page last updated: August 23, 2015

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