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HIV InfectionsPhase 3NCT00147355

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

A Phase 3 study testing ondansetron, ibuprofen, paracetamol, metoclopramide, ibuprofen, paracetamol and Metoclopramide, codeine phosphate, ibuprofen, paracetamol in people with HIV Infections, run by Kirby Institute at 16 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HIV Infections
What is being tested?
ondansetron, ibuprofen, paracetamol, metoclopramide, ibuprofen, paracetamol and Metoclopramide, codeine phosphate, ibuprofen, paracetamol
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
16 sitesin 3 countries
Study dates
Nov 2005to Dec 2008
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

16 sites in 3 countries.

16 sites in 3 countries

Argentina8 sites

  • Hospital General de Agudos JM Ramos Mejia

    Buenos Aires, Buenos Aires, C221

  • FUNCEI

    Buenos Aires, Buenos Aires

  • Hospital Italiano de Buenos Aires

    Buenos Aires, Buenos Aires

  • Hospital Prof. Alejandro Posadas

    Buenos Aires

  • Hospital Interzonal de Agudos San Juan de Dios

    La Plata

  • Hospital Interzonal General de Agudos Oscar Alende

    Mar del Plata

  • Hospital Central

    Mendoza

  • CAICI

    Rosario

Other trials in Argentina

Australia7 sites

  • AIDS Medical Unit

    Brisbane, Queensland, 4002

  • Cairns Base Hospital

    Cairns, Queensland, 4870

  • Gold Coast Sexual Health Clinic

    Gold Coast, Queensland, 4220

  • Carlton Clinic

    Melbourne, Victoria, 3000

  • The Alfred Hospital

    Melbourne, Victoria, 3000

  • Nambour Hospital

    Nambour, Queensland, 4560

  • St. Vincent's Hospital

    Sydney, New South Wales, 2010

Other trials in Australia

Israel1 site

  • Kaplan Medical Center

    Rehovot

Other trials in Israel

About this study

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

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.

Read the 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.

Conditions
HIV Infections
Being tested
ondansetron, ibuprofen, paracetamol, metoclopramide, ibuprofen, paracetamol, Metoclopramide, codeine phosphate, ibuprofen, paracetamol
Keywords
rIL-2-toxicity, interleukin-2 therapy, HIV, Toxicity substudy of ESPRIT
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ondansetron, ibuprofen, paracetamolDrug

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

  • Ondansetron, ibuprofen, paracetamolDrug

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

  • metoclopramide, ibuprofen, paracetamolDrug

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

  • Metoclopramide, codeine phosphate, ibuprofen, paracetamolDrug

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

Study groups in NCT00147355
Study groupRoleWhat they receive
AOtherOndansetron 4mg bid + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle
Receives: Drug: ondansetron, ibuprofen, paracetamol
BOtherOndansetron 4mg bid + codeine phosphate 15mg tds + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle
Receives: Drug: Ondansetron, ibuprofen, paracetamol
DOthermetoclopramide 10mg qds + codeine phosphate 15mg tds + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle
Receives: Drug: Metoclopramide, codeine phosphate, ibuprofen, paracetamol
COthermetoclopramide 10mg qds + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle
Receives: Drug: metoclopramide, ibuprofen, paracetamol

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 6 months

Secondary outcomes (8)

  1. 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

    Measured: 6 months

  2. 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

    Measured: 6 mths

  3. 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

    Measured: 6 months

  4. 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

    Measured: 6 months

  5. 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

    Measured: 6 months

  6. 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

    Measured: 6 months

  7. 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

    Measured: 6 months

  8. 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

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Sep 2005 (estimated)
  2. Study startNov 2005
  3. Primary completionNov 2008
  4. Study completionDec 2008

Why it stopped: 28 of 168 patients only were enrolled, numbers too low to be conclusive

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00147355
Sponsor's protocol ID
ESPRIT TOXIL-2 UNSW PSO 6361
Other IDs
ACTR012605000407695
Status last verified
Apr 2012
First submitted
5 Sep 2005
Last updated
12 Apr 2012
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ondansetron, ibuprofen, paracetamol, metoclopramide, ibuprofen, paracetamol and Metoclopramide, codeine phosphate, ibuprofen, paracetamol in people with HIV Infections, run by Kirby Institute at 16 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 12 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in Argentina, Australia, Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: 28 of 168 patients only were enrolled, numbers too low to be conclusive). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

percentage of planned rIL-2 taken during the first rIL-2 dosing cycle while participating in this substudy. (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00147355.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2012.

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