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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00147355
• Other study ID #: ESPRIT TOXIL-2 UNSW PSO 6361
• Secondary ID: ACTR012605000407
• Status: Terminated
• Phase: Phase 3
• First received: September 5, 2005
• Last updated: April 11, 2012
• Start date: November 2005
• Est. completion date: December 2008

Study information

• Verified date: April 2012
• Source: Kirby Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationIsrael: Israeli Health Ministry Pharmaceutical AdministrationArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaUnited States: Food and Drug Administration
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 28
• Est. completion date: December 2008
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• ondansetron, ibuprofen, paracetamol
ondansetron 4mg bid + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle
• 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
• metoclopramide, ibuprofen, paracetamol
metoclopramide 10mg qds + Ibuprofen 200mg qds + paracetamol 1g qds days 1-6 inclusive of rIL-2 dosing cycle
• 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

Locations

Country	Name	City	State
Argentina	FUNCEI	Buenos Aires
Argentina	Hospital General de Agudos JM Ramos Mejia	Buenos Aires
Argentina	Hospital Italiano de Buenos Aires	Buenos Aires
Argentina	Hospital Prof. Alejandro Posadas	Buenos Aires
Argentina	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
Australia	AIDS Medical Unit	Brisbane	Queensland
Australia	Cairns Base Hospital	Cairns	Queensland
Australia	Gold Coast Sexual Health Clinic	Gold Coast	Queensland
Australia	Carlton Clinic	Melbourne	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Nambour Hospital	Nambour	Queensland
Australia	St. Vincent's Hospital	Sydney	New South Wales
Israel	Kaplan Medical Center	Rehovot

Sponsors (2)

Lead Sponsor	Collaborator
Kirby Institute	The University of New South Wales

Countries where clinical trial is conducted

Argentina,  Australia,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	6 months	No
Secondary	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	6 months	No
Secondary	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	6 mths	No
Secondary	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	6 months	No
Secondary	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	6 months	No
Secondary	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	6 months	Yes
Secondary	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	6 months	Yes
Secondary	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	6 months	No
Secondary	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	6 months	Yes

External Links

•   National Centre in HIV Epidemiology and Clinical Research Homepage