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

Kirby Institute

Status and phase: Terminated; Phase 3

Conditions: HIV Infections

Treatments: Drug: ondansetron, ibuprofen, paracetamol; Drug: metoclopramide, ibuprofen, paracetamol; Drug: Metoclopramide, codeine phosphate, ibuprofen, paracetamol; Drug: Ondansetron, ibuprofen, paracetamol

Study type: Interventional

Funder types: Other

Identifiers

NCT00147355

ESPRIT TOXIL-2 UNSW PSO 6361

ACTR012605000407695

Details and patient eligibility

About

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.

Full 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.

Enrollment: 28 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

---

28 participants in 4 patient groups

A

Other group

Description:

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

Treatment:

Drug: ondansetron, ibuprofen, paracetamol

B

Other group

Description:

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

Treatment:

Drug: Ondansetron, ibuprofen, paracetamol

D

Other group

Description:

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

Treatment:

Drug: Metoclopramide, codeine phosphate, ibuprofen, paracetamol

C

Other group

Description:

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

Treatment:

Drug: metoclopramide, ibuprofen, paracetamol