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

Primary Purpose

HIV Infections

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
ondansetron, ibuprofen, paracetamol
Ondansetron, ibuprofen, paracetamol
metoclopramide, ibuprofen, paracetamol
Metoclopramide, codeine phosphate, ibuprofen, paracetamol
Sponsored by
Kirby Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring rIL-2-toxicity, interleukin-2 therapy, HIV, Toxicity substudy of ESPRIT

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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 Exclusion Criteria: All exclusions for the receipt of rIL-2 on ESPRIT 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.

Sites / Locations

  • Hospital General de Agudos JM Ramos Mejia
  • FUNCEI
  • Hospital Italiano de Buenos Aires
  • Hospital Prof. Alejandro Posadas
  • Hospital Interzonal de Agudos San Juan de Dios
  • Hospital Interzonal General de Agudos Oscar Alende
  • Hospital Central
  • CAICI
  • St. Vincent's Hospital
  • AIDS Medical Unit
  • Cairns Base Hospital
  • Gold Coast Sexual Health Clinic
  • Nambour Hospital
  • Carlton Clinic
  • The Alfred Hospital
  • Kaplan Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Other

Other

Other

Other

Arm Label

A

B

D

C

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Patterns of rIL-2 cycling frequency in the six months after randomisation into the substudy
to explore the patterns of rIL-2 and see if the different adjuntive regimens increase tolerability such that more rIL-2 is taken
Percentage of planned rIL-2 taken during the cycles after the first cycle
this is to assess whether the adjuncts to which the patient was randomised as part of this substudy impact on better tolerability of cycles of rIL-2 beyond the first
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
to see if the adjuncts to which the patient is randomised improve amount of rIL-2 taken compared to the cycle taken prior to enrollment in this substudy
Number of patients with dose modifications during the cycle due to toxicity
to assess whether the adjuncts to which they were randomised reduced the amount of rIL-2 dose modification during the rIL-2 cycle
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
to assess the impact of the randomised adjuntive agents on the predictable side-effects of rIL-2
Grade 1-4 creatinine and sodium changes during and after rIL-2 dosing;
to assess the impact of the randomised adjuntive agents on the predictable effects of rIL-2 in regards to salt and water homeostasis and renal function
Changes in quality of life during and after rIL-2
to assess whether the use of different adjunctive agents impacted on the tolerability of rIL-2 during the cycle and post as perceived by the patients qOL
Incidence of SAE and AE
to assess the incidence of SAE and AEs that are rIL-2 (captured for the main study) and adjunctive agents

Full Information

First Posted
September 5, 2005
Last Updated
April 11, 2012
Sponsor
Kirby Institute
Collaborators
The University of New South Wales
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1. Study Identification

Unique Protocol Identification Number
NCT00147355
Brief Title
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

2. Study Status

Record Verification Date
April 2012
Overall Recruitment Status
Terminated
Why Stopped
28 of 168 patients only were enrolled, numbers too low to be conclusive
Study Start Date
November 2005 (undefined)
Primary Completion Date
November 2008 (Actual)
Study Completion Date
December 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kirby Institute
Collaborators
The University of New South Wales

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
rIL-2-toxicity, interleukin-2 therapy, HIV, Toxicity substudy of ESPRIT

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
28 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Other
Arm Description
Ondansetron 4mg bid + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle
Arm Title
B
Arm Type
Other
Arm Description
Ondansetron 4mg bid + codeine phosphate 15mg tds + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle
Arm Title
D
Arm Type
Other
Arm Description
metoclopramide 10mg qds + codeine phosphate 15mg tds + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle
Arm Title
C
Arm Type
Other
Arm Description
metoclopramide 10mg qds + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle
Intervention Type
Drug
Intervention Name(s)
ondansetron, ibuprofen, paracetamol
Intervention Description
ondansetron 4mg bid + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle
Intervention Type
Drug
Intervention Name(s)
Ondansetron, ibuprofen, paracetamol
Intervention Description
Ondansetron 4mg bid + codeine phosphate 15mg tds + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle
Intervention Type
Drug
Intervention Name(s)
metoclopramide, ibuprofen, paracetamol
Intervention Description
metoclopramide 10mg qds + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle
Intervention Type
Drug
Intervention Name(s)
Metoclopramide, codeine phosphate, ibuprofen, paracetamol
Intervention Description
metoclopramide 10mg qds + codeine phosphate 15mg tds + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle
Primary Outcome Measure Information:
Title
percentage of planned rIL-2 taken during the first rIL-2 dosing cycle while participating in this substudy.
Description
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
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Patterns of rIL-2 cycling frequency in the six months after randomisation into the substudy
Description
to explore the patterns of rIL-2 and see if the different adjuntive regimens increase tolerability such that more rIL-2 is taken
Time Frame
6 months
Title
Percentage of planned rIL-2 taken during the cycles after the first cycle
Description
this is to assess whether the adjuncts to which the patient was randomised as part of this substudy impact on better tolerability of cycles of rIL-2 beyond the first
Time Frame
6 mths
Title
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
Description
to see if the adjuncts to which the patient is randomised improve amount of rIL-2 taken compared to the cycle taken prior to enrollment in this substudy
Time Frame
6 months
Title
Number of patients with dose modifications during the cycle due to toxicity
Description
to assess whether the adjuncts to which they were randomised reduced the amount of rIL-2 dose modification during the rIL-2 cycle
Time Frame
6 months
Title
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
Description
to assess the impact of the randomised adjuntive agents on the predictable side-effects of rIL-2
Time Frame
6 months
Title
Grade 1-4 creatinine and sodium changes during and after rIL-2 dosing;
Description
to assess the impact of the randomised adjuntive agents on the predictable effects of rIL-2 in regards to salt and water homeostasis and renal function
Time Frame
6 months
Title
Changes in quality of life during and after rIL-2
Description
to assess whether the use of different adjunctive agents impacted on the tolerability of rIL-2 during the cycle and post as perceived by the patients qOL
Time Frame
6 months
Title
Incidence of SAE and AE
Description
to assess the incidence of SAE and AEs that are rIL-2 (captured for the main study) and adjunctive agents
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: All exclusions for the receipt of rIL-2 on ESPRIT 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sarah L Pett, M.D
Organizational Affiliation
Kirby Institute, Faculty of Medicine, University of New South Wales, Sydney, Australia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital General de Agudos JM Ramos Mejia
City
Buenos Aires
ZIP/Postal Code
C221
Country
Argentina
Facility Name
FUNCEI
City
Buenos Aires
Country
Argentina
Facility Name
Hospital Italiano de Buenos Aires
City
Buenos Aires
Country
Argentina
Facility Name
Hospital Prof. Alejandro Posadas
City
Buenos Aires
Country
Argentina
Facility Name
Hospital Interzonal de Agudos San Juan de Dios
City
La Plata
Country
Argentina
Facility Name
Hospital Interzonal General de Agudos Oscar Alende
City
Mar del Plata
Country
Argentina
Facility Name
Hospital Central
City
Mendoza
Country
Argentina
Facility Name
CAICI
City
Rosario
Country
Argentina
Facility Name
St. Vincent's Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
AIDS Medical Unit
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4002
Country
Australia
Facility Name
Cairns Base Hospital
City
Cairns
State/Province
Queensland
ZIP/Postal Code
4870
Country
Australia
Facility Name
Gold Coast Sexual Health Clinic
City
Gold Coast
State/Province
Queensland
ZIP/Postal Code
4220
Country
Australia
Facility Name
Nambour Hospital
City
Nambour
State/Province
Queensland
ZIP/Postal Code
4560
Country
Australia
Facility Name
Carlton Clinic
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Facility Name
The Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Facility Name
Kaplan Medical Center
City
Rehovot
Country
Israel

12. IPD Sharing Statement

Links:
URL
http://www.med.unsw.edu.au/nchecr/
Description
National Centre in HIV Epidemiology and Clinical Research Homepage

Learn more about this trial

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

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