Clinical trial NCT00147355: Toxicity Substudy of Evaluation of Subcutaneous Proleukin in a Randomised International Trial (ESPRIT): TOXIL-2 Substudy
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: HIV Infections
Keywords: rIL-2-toxicity
interleukin-2 therapy
HIV
Toxicity substudy of ESPRIT
Lead sponsor: Kirby Institute
Sponsor class: OTHER_GOV
Collaborators: name: The University of New South Wales
First posted: 2005-09-07
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: percentage of planned rIL-2 taken during the first rIL-2 dosing cycle while participating in this substudy.
timeFrame: 6 months
Secondary outcomes:
measure: Patterns of rIL-2 cycling frequency in the six months after randomisation into the substudy
timeFrame: 6 months
measure: Percentage of planned rIL-2 taken during the cycles after the first cycle
timeFrame: 6 mths
measure: 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
timeFrame: 6 months
measure: Number of patients with dose modifications during the cycle due to toxicity
timeFrame: 6 months
measure: 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
timeFrame: 6 months
measure: Grade 1-4 creatinine and sodium changes during and after rIL-2 dosing;
timeFrame: 6 months
measure: Changes in quality of life during and after rIL-2
timeFrame: 6 months
measure: Incidence of SAE and AE
timeFrame: 6 months
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Hospital General de Agudos JM Ramos Mejia
city: Buenos Aires
country: Argentina
facility: FUNCEI
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Buenos Aires
country: Argentina
facility: Hospital Prof. Alejandro Posadas
city: La Plata
country: Argentina
facility: Hospital Interzonal de Agudos San Juan de Dios
city: Mar del Plata
country: Argentina
facility: Hospital Interzonal General de Agudos Oscar Alende
city: Mendoza
country: Argentina
facility: Hospital Central
city: Rosario
country: Argentina
facility: CAICI
city: Sydney
country: Australia
facility: St. Vincent's Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: AIDS Medical Unit
state: Queensland
city: Cairns
country: Australia
facility: Cairns Base Hospital
state: Queensland
city: Gold Coast
country: Australia
facility: Gold Coast Sexual Health Clinic
state: Queensland
city: Nambour
country: Australia
facility: Nambour Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Carlton Clinic
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Rehovot
country: Israel
facility: Kaplan Medical Center
Study officials:
affiliation: Kirby Institute, Faculty of Medicine, University of New South Wales, Sydney, Australia
name: Sarah L Pett, M.D
role: PRINCIPAL_INVESTIGATOR
References: