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Toxicity Substudy of Evaluation of Subcutaneous Proleukin in a Randomised International Trial (ESPRIT): TOXIL-2 Substudy

Information source: The National Centre in HIV Epidemiology and Clinical Research
Information obtained from ClinicalTrials.gov on November 03, 2008
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: HIV Infections

Intervention: Metoclopramide (Drug); Ondansetron (Drug); Paracetamol (Drug); Codeine phosphate (Drug); Ibuprofen (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: The National Centre in HIV Epidemiology and Clinical Research

Official(s) and/or principal investigator(s):
Sarah L Pett, M.D, Principal Investigator, Affiliation: National Centre in HIV Epidemiology and Clinical Research, Faculty of Medicine, University of New South Wales, Sydney, Australia

Overall contact:
Sarah Pett, M.D, Phone: +61 2 9385 0900, Ext: 50909, Email: spett@nchecr.unsw.edu.au

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: Treatment, Randomized, Open Label, Active Control, Factorial Assignment, Efficacy Study

Primary outcome:

The percentage (%) of planned rIL-2 taken during the first rIL-2 dosing cycle while participating in this substudy

rIL-2 uptake will be 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:

Mean amount of rIL-2 taken during the cycle in million international units (MIU)

Number of cycles initiated during the 6 month period

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

Mean time between receipt of rIL-2 on this substudy and the last dosing cycle of rIL-2 prior to entry into the substudy

Number of patients with dose modifications during the cycle due to toxicity

Percentage of patients completing any cycle initiated

Number of patients with grade 1-4 gastrointestinal (GI) toxicities

Number of patients with grade 1-4 constitutional upset (defined as any or all of the following: flu-like illness/fever/myalgia/arthralgia/headache)

Number of patients with grade 1-4 oedema and/or other clinical manifestations of capillary leak syndrome, eg pulmonary oedema

Number of patients with >= 10% weight gain during rIL-2 dosing

Grade 1-4 creatinine changes during and after rIL-2 dosing

Grade 1-4 serum sodium changes during and after rIL-2 dosing

Changes in quality of life during and after rIL-2

Patterns of use of breakthrough adjunctive therapies

Safety of adjunctive agents as measured by grade 1-4 toxicity attributed to any of the adjunctive agents

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

Number of patients indicating willingness to receive further rIL-2 following first rIL-2 cycle

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.

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

Sarah Pett, M.D, Phone: +61 2 9385 0900, Ext: 50909, Email: spett@nchecr.unsw.edu.au

Hospital Interzonal General de Agudos Oscar Alende, Mar del Plata, Argentina; Not yet recruiting
Jorge A Corral, M.D, Phone: +54 (223) 494 2114, Email: corralfucks@arnet.com.ar

Hospital Prof. Alejandro Posadas, Buenos Aires, Argentina; Not yet recruiting
Hector E Laplume, M.D, Phone: +54 (11) 44699300, Email: hlaplume@speedy.com.ar

CAICI, Rosario, Argentina; Not yet recruiting
Sergio Lupo, M.D, Phone: +54 (341) 424 8045, Email: sergiolupo@arnet.com.ar

Hospital Interzonal de Agudos San Juan de Dios, La Plata, Argentina; Not yet recruiting
Lucila Massera, M.D, Phone: +54 (221) 420 6223, Email: lucilamassera@topmail.com.ar

Hospital Central, Mendoza, Argentina; Not yet recruiting
Victor Bittar, M.D, Phone: +54 (261) 4201920, Email: victorbittar@ciudad.com.ar

Hospital General de Agudos JM Ramos Mejia, Buenos Aires C221, Argentina; Not yet recruiting
Marcelo H Losso, M.D, Phone: +5411-4931-5252, Email: mlosso@hivramos.org.ar

Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; Not yet recruiting
Waldo Belloso, M.D, Phone: +54 (11) 49590393, Email: waldo.belloso@hospitalitaliano.org.ar

FUNCEI, Buenos Aires, Argentina; Not yet recruiting
Gustavo Lopardo, M.D, Phone: +54 (11) 5236 7772, Email: glopardo@intramed.net.ar

Kaplan Medical Center, Rehovot, Israel; Not yet recruiting
Zev Sthoeger, M.D, Phone: +972 (8) 944 1444, Email: sthoeger@012.net.il

St. Vincent's Hospital, Sydney, New South Wales 2010, Australia; Recruiting
Sarah L Pett, M.D, Phone: +61 2 9385 0900, Ext: 50909, Email: spett@nchecr.unsw.edu.au
David A Cooper, M.D, Phone: +61 2 9385 0900
Sarah L Pett, M.D, Principal Investigator

Nambour Hospital, Nambour, Queensland 4560, Australia; Recruiting
David Sowden, Phone: +61 (07) 5476-2489, Email: david_sowden@health.qld.gov.au

AIDS Medical Unit, Brisbane, Queensland 4002, Australia; Recruiting
Mark Kelly, M.D, Phone: +61 (07) 3224-5525, Email: mark_d_kelly@health.qld.gov.au
Hugo Ree, M.D, Phone: (07) 3224-5526, Email: hugo_ree@health.qld.gov.au

Gold Coast Sexual Health Clinic, Gold Coast, Queensland 4220, Australia; Not yet recruiting
John Chuah, M.D, Phone: 07-5576-9031, Email: chuahj@health.qld.gov.au

Cairns Base Hospital, Cairns, Queensland 4870, Australia; Not yet recruiting
Darren Russell, M.D
Kay Haig, M.D, Phone: +61 (07) 4050-6205, Email: kay_haig@health.qld.gov.au

The Alfred Hospital, Melbourne, Victoria 3000, Australia; Recruiting
Jenny Hoy, Phone: +61 (03) 9276-6900, Email: jennifer.hoy@med.monash.edu.au

Carlton Clinic, Melbourne, Victoria 3000, Australia; Recruiting
Jonathan Anderson, M.D, Phone: +61 (03) 9347-9422, Email: jonathan.anderson@maynemc.com

Additional Information

National Centre in HIV Epidemiology and Clinical Research Homepage

Starting date: November 2005
Ending date: September 2007
Last updated: June 14, 2006

Page last updated: November 03, 2008

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