Sustained Virological Suppression and Improvement of Adverse Events of Switching to Raltegravir Study (TaISENWITCH)

Study Description

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Brief Summary:

Switching from the ritonavir-boosted protease inhibitor component to raltegravir in stable HIV-infected adult patients receiving combination therapy will demonstrate improved clinical tolerability or lipid profiles with sustained plasma virological response (<50 copies/ml).

Condition or disease	Intervention/treatment	Phase
HIV Infection; Adverse Drug Reaction; Quality of Life	Drug: Raltegravir switch	Phase 4

Detailed Description:

A. Objectives To compare the treatment-emerged AEs and virological suppression after switch to raltegravir-based therapy in stable HIV-infected patients who receiving ritonavir-boosted protease inhibitor antiretroviral regimen

Primary endpoints:

1) The changes in overall incidence and severity of patient-reported clinical adverse events (based on "symptom distress module) after switch to raltegravir-based therapy.

Secondary endpoints:

1. The proportion of patients who are free of "virological failure" at week 48 after switch
2. The change from baseline in CD4 cell counts at week 48 after switch
3. The change in quality of life by assess the changes in the domain scores of MOS-HIV questionnaire at baseline and different study time points.
4. The changes in laboratory adverse event, e.g., the mean percent changes from baseline to 48 weeks in plasma lipid profile (total cholesterol, LDLCholesterol, HDL Cholesterol, triglycerides) after switch
5. The proportion of patients who are free of "treatment failure" at week 48 after switch

Safety endpoints

1. Incidence of adverse events
2. The proportion of patients with treatment-related grade 3 or 4 adverse events and laboratory abnormalities

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	107 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Single Arm Study to Assess the Sustained Virological Suppression and Improvement of Treatment-emerged Adverse Events of Switching to Raltegravir in Stable HIV-infected Patients on Ritonavir-boosted Protease Inhibitor Regimen
Study Start Date :	July 2012
Actual Primary Completion Date :	February 2015
Actual Study Completion Date :	February 2015

Arms and Interventions

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Arm	Intervention/treatment
Raltegravir switch; Isentress (400mg) bid + 2 NRTI (at least 2 nucleoside or nucleotide reverse transcriptase inhibitors and no other protease inhibitors)	Drug: Raltegravir switch; Isentress (400mg) bid + 2 NRTI (at least 2 nucleoside or nucleotide reverse transcriptase inhibitors and no other protease inhibitors); Other Name: Isentress

Outcome Measures

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Primary Outcome Measures :

1. The proportion of patient-reported clinical adverse events [ Time Frame: Week 4, 12-16, 28-32, 48 ]
   The proportion of patient-reported clinical adverse events in total and by severity (based on symptom distress module) at 4 weeks, The proportion of patient-reported clinical adverse events in total and by severity (based on symptom distress module) at 12-16 weeks, The proportion of patient-reported clinical adverse events in total and by severity (based on symptom distress module) at 28-32 weeks, The proportion of patient-reported clinical adverse events in total and by severity (based on symptom distress module) at 48 weeks

Secondary Outcome Measures :

1. The proportion of patients who are free of "virological failure" [ Time Frame: Week 4, 12-16, 28-32, 48 ]
   The proportion of patients who are free of "virological failure" at week 4 after switch, The proportion of patients who are free of "virological failure" at week 12-16 after switch, The proportion of patients who are free of "virological failure" at week 28-32 after switch, The proportion of patients who are free of "virological failure" at week 48 after switch
2. The change from baseline in CD4 cell counts [ Time Frame: Week 4, 12-16, 28-32, 48 ]
   The change from baseline in CD4 cell counts at week 4 after switch, The change from baseline in CD4 cell counts at week 12-16 after switch, The change from baseline in CD4 cell counts at week 28-32 after switch, The change from baseline in CD4 cell counts at week 48 after switch
3. the change from baseline in life quality (based on the MOS-HIV questionnaire) [ Time Frame: week 12-16, 48 ]
   The change from baseline in quality of life (based on the MOS-HIV questionnaire) at week 12-16 after switch, The change from baseline in quality of life (based on the MOS-HIV questionnaire) at week 48 after switch.
4. The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) [ Time Frame: Week 4, 12-16, 28-32, 48 ]
   The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 4 weeks, The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 12-16 weeks, The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 28-32 weeks, The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 48 weeks
5. The proportion of patients with treatment failure [ Time Frame: Week 4, 12-16, 28-32, 48 ]
   The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 4 weeks, The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 12-16 weeks, The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 28-32 weeks, The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 48 weeks

Eligibility Criteria

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Ages Eligible for Study:	20 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Patients who are infected with HIV-1
• Ages at least 20 years
• Patients are currently receiving a ritonavir-boosted PI-based regimen, including lopinavir, atazanavir, or darunavir, plus at least 2 antiretroviral agents (NRTIs)
• Patient complained of treatment-emerged clinical adverse events or abnormal lipid profile
• Patients with plasma HIV-1 viral RNA below 50 copies per ml for at least 6 months

Exclusion Criteria:

• Patient with known history of contraindication or hypersensitivity to any component of the study regimen
• Patients with acute or decompensated chronic hepatitis in the previous 6 months
• Patients with chronic hepatitis and serum aminotransferase concentrations are more than 5 times the upper limit of the normal range
• Patients with renal insufficiency (patients need dialysis or have serum creatinine concentrations of more than twice the upper limit of the normal range
• Current alcohol or substance abuse (patients receiving methadone for the management of withdrawal symptoms due to substance abuse are allowed )
• Patients have failed previous regimens (prior to starting the current 2NRTI+PI/r regimen they are currently on)
• Patient's viral load have not been consistently <50 copies per ml for 6 months or longer.
• Patients initiated lipid lowering agents during the preceding 3 months
• Patients with any medical disorder or history of any illness which, in the opinion of the investigator, that the use of study medications is contraindicated or might confound the results of the study or pose additional risk in administering study drugs to the patient
• Pregnant, wish to become pregnant during the study period or breastfeeding women
• Patients who are lack of expectation to maintain assigned study medication during study period
• Patients who have received therapy with investigational drugs in the previous 3 months

Contacts and Locations

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Locations

Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung, Taiwan, 807
E-Da Hospital
Kaohsiung, Taiwan, 824
China Medical University Hospital
Taichung, Taiwan, 40447
National Cheng Kung University Hospital
Tainan, Taiwan, 704
National Taiwan University Hospital
Taipei, Taiwan, 10048
Taipei City Hospital
Taipei, Taiwan, 108
Chang Gung Memorial Hospital at Linkou
Taoyuan, Taiwan, 333

Sponsors and Collaborators

Lin, Hsi-Hsun, M.D.

Investigators

Principal Investigator:	Hsi-Hsun Lin, MD	E-DA Hospital

More Information

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Publications:

Walensky RP. The survival benefits of AIDS treatment in the US. J Infect Dis 2006;194:11-19 Lennox JL. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection. Lancet 2009;374:796-806 Steigbigel RT. Long-term efficacy and safety of Raltegravir combined with optimized background therapy in treatment-experienced patients with drug-resistant HIV infection. Clin Infect Dis 2010;50:605-12 Eron JJ. Switch to raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2). Lancet 2010;375:396-407 Martinex E. Substitution of raltegravir for ritonavir-boosted protease inhibitors in HIV-infected patients: the SPIRAL study. AIDS 2010, 24:1697-1707 Division of AIDS(DAIDS). Toxicity guideline for adults. http://rcc.tech-res.com/safetyand pharmacovigilance(accessed Apr 15, 2011)

Responsible Party:	Lin, Hsi-Hsun, M.D.
ClinicalTrials.gov Identifier:	NCT01679964 History of Changes
Other Study ID Numbers:	MISP40301; MISP 40301 ( Other Grant/Funding Number: MISP 40301 )
First Posted:	September 6, 2012
Last Update Posted:	September 15, 2016
Last Verified:	September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by Lin, Hsi-Hsun, M.D.:

HIV infection; Raltegravir; Adverse event; Life quality

Additional relevant MeSH terms:

HIV Infections; Drug-Related Side Effects and Adverse Reactions; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Chemically-Induced Disorders; Raltegravir Potassium	Protease Inhibitors; HIV Protease Inhibitors; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors