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

NCT00147355 | Terminated Phase 3 DMC

• 2 other identifiers: ESPRIT TOXIL-2 UNSW PSO 6361ACTR012605000407695
• Study Type: interventional
• Target: 28
• Locations: 3 countries
• Sites: 16

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.

Conditions

HIV Infections

Keywords

rIL-2-toxicity; interleukin-2 therapy; HIV; Toxicity substudy of ESPRIT

Outcome Measures

Primary Outcomes (1)

• 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

  6 months

Secondary Outcomes (8)

• Patterns of rIL-2 cycling frequency in the six months after randomisation into the substudy

  6 months

• Percentage of planned rIL-2 taken during the cycles after the first cycle

  6 mths

• 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

  6 months

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

  6 months

• 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

  6 months

Study Arms (4)

A

OTHER

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

Drug: ondansetron, ibuprofen, paracetamol

B

OTHER

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

Drug: Ondansetron, ibuprofen, paracetamol

D

OTHER

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

Drug: Metoclopramide, codeine phosphate, ibuprofen, paracetamol

C

OTHER

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

Drug: metoclopramide, ibuprofen, paracetamol

Interventions

Ondansetron, ibuprofen, paracetamol DRUG

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

A

metoclopramide, ibuprofen, paracetamol DRUG

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

C

Metoclopramide, codeine phosphate, ibuprofen, paracetamol DRUG

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

D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients participating in ESPRIT and randomised to the rIL-2 arm, who:
• Are not at CD4+ T-cell target for the protocol
• Have not received rIL-2 for \> 2 months
• 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
• Are considered by the Investigator as medically safe to receive further dosing with rIL-2
• Are willing to receive further dosing with rIL-2 at the dose specified by the Investigator
• Are willing to sign informed consent to participate in the substudy

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Kirby Institute: lead
• The University of New South Wales: collaborator

Study Sites (16)

Hospital General de Agudos JM Ramos Mejia

Buenos Aires, Buenos Aires, C221, Argentina

Location

FUNCEI

Buenos Aires, Buenos Aires, Argentina

Location

Hospital Italiano de Buenos Aires

Buenos Aires, Buenos Aires, Argentina

Location

Hospital Prof. Alejandro Posadas

Buenos Aires, Argentina

Location

Hospital Interzonal de Agudos San Juan de Dios

La Plata, Argentina

Location

Hospital Interzonal General de Agudos Oscar Alende

Mar del Plata, Argentina

Location

Hospital Central

Mendoza, Argentina

Location

CAICI

Rosario, Argentina

Location

St. Vincent's Hospital

Sydney, New South Wales, 2010, Australia

Location

AIDS Medical Unit

Brisbane, Queensland, 4002, Australia

Location

Cairns Base Hospital

Cairns, Queensland, 4870, Australia

Location

Gold Coast Sexual Health Clinic

Gold Coast, Queensland, 4220, Australia

Location

Nambour Hospital

Nambour, Queensland, 4560, Australia

Location

Carlton Clinic

Melbourne, Victoria, 3000, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3000, Australia

Location

Kaplan Medical Center

Rehovot, Israel

Location

Related Links

• National Centre in HIV Epidemiology and Clinical Research Homepage

MeSH Terms

Conditions

HIV Infections

Interventions

Ondansetron; Ibuprofen; Acetaminophen; Metoclopramide; Codeine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Acetanilides; Anilides; Amides; Aniline Compounds; Amines; Benzamides; para-Aminobenzoates; Aminobenzoates; Benzoates; Chlorobenzoates; Hydroxybenzoate Ethers; Hydroxybenzoates; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenyl Ethers; Phenols; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Sarah L Pett, M.D

  Kirby Institute, Faculty of Medicine, University of New South Wales, Sydney, Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2005
• First Posted: September 7, 2005
• Study Start: November 1, 2005
• Primary Completion: November 1, 2008
• Study Completion: December 1, 2008
• Last Updated: April 12, 2012

Record last verified: 2012-04

Locations

AU (7); AR (8); IL (1)