Neurological Monitoring in Patients Switching From Dolutegravir Based Regimen to Bictegravir Based Regimen

HIV-1-infection Clinical Trial

— DOBINeuro  

Official title:

The Effects of Switching From Dolutegravir/Lamivudine/Abacavir (d/l/a) to Bictegravir/Emtricitabine/Tenofovir Alafenamide (b/f/Taf) in Patients With Suppressed Viral Load on Neuropsychiatric Side Effects and Neurocognitive Function

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04155554
• Other study ID #: 2018-004885-32
• Status: Recruiting
• Phase: Phase 3
• Start date: January 29, 2020
• Est. completion date: July 2021

Study information

• Verified date: January 2020
• Source: Azienda Ospedaliera Universitaria Senese
• Contact: Barbara Rossetti, PhD
• Phone: +393201437658
• Email: barbara.rossetti[@]ao-siena.toscana.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Prospective, randomized study (1: 1), open-label, controlled, phase 3, multicenter, non-profit. The hypothesis of the present study is that bictegravir is associated with a lower incidence and severity of neuropsychiatric symptoms than dolutegravir.

Description:

Prospective, randomized study (1: 1), open-label, controlled, phase 3, multicenter, non-profit. The hypothesis of the present study is that bictegravir is associated with a lower incidence and severity of neuropsychiatric symptoms than dolutegravir. The main outcome measure will be a global severity index (GSI) of neuropsychiatric symptoms arising from 10 symptom domains, including somatization, obsessive-compulsiveness, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, psychoticism. The secondary outcomes are to compare, between arms and during follow up, neuropsychiatric symptoms severity, neurocognitive performance, changes in self-reported symptoms, adherence and HR-QoL, correlation between symptoms (neuropsychiatric and other), drug exposure and HR-QoL, proportion of adverse events, proportion of virological failures and antiretrovirals resistance at virological failure.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: July 2021
• Est. primary completion date: August 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age >18 years

• HIV-1 infection

• HIV RNA <50 copies/mL >12 months (including patients with 1 blip 50-200 cp/mL before screening, not confirmed)

• On treatment with dolutegravir/abacavir/lamivudine >6 months

Exclusion Criteria:

• Previous AIDS events

• Pregnancy or pregnancy plan

• Decompensated cirrhosis (B or C CPT status)

• Intake of alcohol, substances, other drugs that may affect neurocognitive performances

• Necessity to receive drugs that may require dosing adjustment of dolutegravir or bictegravir

• Certified diagnosis of major depression, psychosis, history of suicidal attempts

• Treatment with antidepressants or antipsychotic drugs

• History of virological failure with INSTIs

• Lack of knowledge of italian language

• Impossibility to obtain informed written consent

• HBsAg positivity

• Estimated glomerular filtration rate by CK-EPI <50 mL/min per 1.73 m2

Related Conditions & MeSH terms

• HIV-1-infection

Intervention

Drug:
• Bictegravir/emtricitabine/tenofovir alafenamide
Switch patients from dolutegravir/lamivudine/abacavir to bictegravir/emtricitabine/tenefovir alafenamide to study neuropsychiatric side effects and neurocognitive function
• Dolutegravir/lamivudine/abacavir
Continuing dolutegravir/lamivudine/abacavir to study neuropsychiatric side effects and neurocognitive function

Locations

Country	Name	City	State
Italy	Barbara Rossetti	Siena

Sponsors (5)

Lead Sponsor	Collaborator
Azienda Ospedaliera Universitaria Senese	Azienda Ospedaliera San Paolo, Catholic University of the Sacred Heart, Ospedale Amedeo di Savoia, Ospedale Policlinico San Martino

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	neuropsychiatric symptoms severity in 3 months	change in neuropsychiatric symptoms severity, using the Symptom Checklist-90-R, 3 months after switching to bictegravir or continuing dolutegravir (on treatment analysis).	3 months
Secondary	neuropsychiatric symptoms severity in 3 and 12 months	change in neuropsychiatric symptoms severity, each of the 10 symptoms analyzed separately using the Symptom Checklist-90-R, 3 and 12 months after switching to bictegravir or dolutegravir (on treatment analysis)	12 months
Secondary	Mini International Neuropsychiatric Interview Plus subscale for suicide risk	change in neuropsychiatric symptoms severity, using the Mini International Neuropsychiatric Interview Plus subscale for suicide risk, 3 and 12 months after switching to bictegravir or dolutegravir (on treatment analysis). Suicide risk (five questions, score range 0-33 points) in the last 30 days was classified as low (1-5), moderate (6-9), or high (10).	12 months
Secondary	neurocognitive performance	change in neurocognitive performance, using a comprehensive and validated neuropsychological battery, 12 months after switching to bictegravir or dolutegravir (on treatment analysis).; The neurocognitive performance is calculated by averaging the individual deficit scores from each neurocognitive test. Deficit scores for each test were calculated from age-, education-, -adjusted raw scores.	12 months
Secondary	neurocognitive impairment and neuropsychiatric symptoms	comparison of the inter-arm and intra-arm incidence of neurocognitive impairment (on the basis of Frascati criteria) at 12 months and neuropsychiatric symptoms (using the Symptom Checklist-90-R) at 3 (on treatment analysis) and 12 months (ITT-exposed, using LOCF)	12 months
Secondary	self-reported symptoms (21 items, 0-5 points for each), adherence (0-100%) and HR-QoL (9 items, 0-5 points for each)	changes in self-reported symptoms, adherence and HR-QoL (using validated questionnaires) during the first year of follow up (ITT-exposed, using LOCF).	12 months
Secondary	drug exposure	correlation between symptoms (neuropsychiatric and other), drug exposure and HR-QoL during the first year of follow up (ITT-exposed, using LOCF).	12 months
Secondary	adverse events	proportion of adverse events and serious adverse events and of patients discontinuing due to side effects in both arms	12 months
Secondary	virological failures	proportion of virological failures and antiretrovirals resistance at virological failure	12 months
Secondary	Treatment Satisfaction	change in Treatment Satisfaction between arms as per specific questionnaire (TSQM Version 1.4, 15 questions, from 0 to 79 points as maximum)	12 months