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
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 28
- 试验地点
- 16
- 主要终点
- percentage of planned rIL-2 taken during the first rIL-2 dosing cycle while participating in this substudy.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
A
Ondansetron 4mg bid + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle
干预措施: Ondansetron, ibuprofen, paracetamol (Drug)
B
Ondansetron 4mg bid + codeine phosphate 15mg tds + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle
干预措施: Ondansetron, ibuprofen, paracetamol (Drug)
D
metoclopramide 10mg qds + codeine phosphate 15mg tds + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle
干预措施: Metoclopramide, codeine phosphate, ibuprofen, paracetamol (Drug)
C
metoclopramide 10mg qds + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle
干预措施: metoclopramide, ibuprofen, paracetamol (Drug)
结局指标
主要结局
percentage of planned rIL-2 taken during the first rIL-2 dosing cycle while participating in this substudy.
时间窗: 6 months
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
次要结局
- 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)
- Grade 1-4 creatinine and sodium changes during and after rIL-2 dosing;(6 months)
- Changes in quality of life during and after rIL-2(6 months)
- Incidence of SAE and AE(6 months)