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

This study has been terminated.
(28 of 168 patients only were enrolled, numbers too low to be conclusive)
Sponsor:
Collaborator:
The University of New South Wales
Information provided by (Responsible Party):
Kirby Institute
ClinicalTrials.gov Identifier:
NCT00147355
First received: September 5, 2005
Last updated: April 11, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: ondansetron, ibuprofen, paracetamol
Drug: Ondansetron, ibuprofen, paracetamol
Drug: metoclopramide, ibuprofen, paracetamol
Drug: Metoclopramide, codeine phosphate, ibuprofen, paracetamol
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Kirby Institute:

Primary Outcome Measures:
  • percentage of planned rIL-2 taken during the first rIL-2 dosing cycle while participating in this substudy. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 mths ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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; [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    to assess the incidence of SAE and AEs that are rIL-2 (captured for the main study) and adjunctive agents


Enrollment: 28
Study Start Date: November 2005
Study Completion Date: December 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
A
Ondansetron 4mg bid + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle
Drug: ondansetron, ibuprofen, paracetamol
ondansetron 4mg bid + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle
B
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
Ondansetron 4mg bid + codeine phosphate 15mg tds + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle
D
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
metoclopramide 10mg qds + codeine phosphate 15mg tds + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle
C
metoclopramide 10mg qds + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle
Drug: metoclopramide, ibuprofen, paracetamol
metoclopramide 10mg qds + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00147355

Locations
Argentina
FUNCEI
Buenos Aires, Argentina
Hospital Prof. Alejandro Posadas
Buenos Aires, Argentina
Hospital Italiano de Buenos Aires
Buenos Aires, Argentina
Hospital General de Agudos JM Ramos Mejia
Buenos Aires, Argentina, C221
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
Australia, New South Wales
St. Vincent's Hospital
Sydney, New South Wales, Australia, 2010
Australia, Queensland
AIDS Medical Unit
Brisbane, Queensland, Australia, 4002
Cairns Base Hospital
Cairns, Queensland, Australia, 4870
Gold Coast Sexual Health Clinic
Gold Coast, Queensland, Australia, 4220
Nambour Hospital
Nambour, Queensland, Australia, 4560
Australia, Victoria
The Alfred Hospital
Melbourne, Victoria, Australia, 3000
Carlton Clinic
Melbourne, Victoria, Australia, 3000
Israel
Kaplan Medical Center
Rehovot, Israel
Sponsors and Collaborators
Kirby Institute
The University of New South Wales
Investigators
Principal Investigator: Sarah L Pett, M.D Kirby Institute, Faculty of Medicine, University of New South Wales, Sydney, Australia
  More Information

Additional Information:
No publications provided

Responsible Party: Kirby Institute
ClinicalTrials.gov Identifier: NCT00147355     History of Changes
Other Study ID Numbers: ESPRIT TOXIL-2 UNSW PSO 6361, ACTR012605000407695
Study First Received: September 5, 2005
Last Updated: April 11, 2012
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Israel: Israeli Health Ministry Pharmaceutical Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
United States: Food and Drug Administration

Keywords provided by Kirby Institute:
rIL-2-toxicity
interleukin-2 therapy
HIV
Toxicity substudy of ESPRIT

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Acetaminophen
Ibuprofen
Codeine
Metoclopramide
Ondansetron
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Antipyretics
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Antitussive Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on August 28, 2014