Back to resultsA Phase IV Study to Assess the Impact of the Change of Antiretroviral Treatment From Dual Therapy to Triple Therapy on Inflammation in Patients With HIV Infection (InSTINCT)
Primary Purpose
HIV Infections
Status
Recruiting
Phase
Phase 4
Locations
Spain
Study Type
Interventional
Intervention
Dual Therapy
Triple therapy
Sponsored by
About this trial
This is an interventional treatment trial for HIV Infections
Eligibility Criteria
Inclusion Criteria:
- Men and women ≥ 18 years
- Confirmed and documented diagnosis of HIV-1 infection
- Virological suppression of more than 48 weeks (confirmed with HIV RNA <50 copies / ml). The determination of the CV of a routine prior analysis of ≤ 12 weeks prior to signature of consent.
- ART in stable dual therapy (> 48 weeks) with DTG + 3TC
- Signed informed consent
- Negative pregnancy test in urine or blood
Exclusion Criteria:
- Inability to obtain written informed consent to participate in the study
- Pregnant or breastfeeding women or those who intend to become pregnant during the study period and do not undertake to use proven contraceptive methods.
- Any suspicion or confirmation of resistance to TAF, 3TC, FTC, DTG or BIC. In case of have a study of baseline resistance mutations prior to the start of ART has to rule out resistance to investigational drugs.
- Patients with hypersensitivity to any excipient used with TAF, FTC, DTG or BIC
- Any chronic autoimmune or inflammatory disease
- Use of immunomodulatory or immunosuppressive agents, including steroids Chronic treatment with aspirin, statins and other anti-inflammatory agents
- Any acute infection in the last 2 months
- Estimated glomerular filtration rate (TFGe) <30 mg / ml / m2 measured by any of the formulas available. The determination of the TFGe of a previous routine analysis of ≤ 12 weeks prior to signing the consent is allowed
- Contraindication for the use of TAF
- Clinical condition of the patient in rapid deterioration or the investigator considers that there is no reasonable hope that the patient will finish the study
- Simultaneous participation in another clinical trial or research study that requires the need of treatment with other drugs outside the study or interfere with the visits of the same.
- Any situation that, in the opinion of the investigator, may interfere with the patient's ability to meet the treatment schedule and protocol evaluations
Sites / Locations
- Hospital General de Alicante
- H. Clinic i Provincial
- Hospital de BellvitgeRecruiting
- Hospital Univ. Vall D'Hebron
- Hospital Reina Sofia
- Hospital Clínico San Carlos
- Hospital Fundación Jimenez Diaz
- Hospital Univ. de La Princesa
- Hospital Univ. La PazRecruiting
- Hospital Univ. Ramón y CajalRecruiting
- Hospital Virgen de las NievesRecruiting
- Hospital Regional Carlos Haya
- Hospital Virgen de la Victoria
- Hospital de Santiago
- Hospital Univ. Virgen del Rocio
- Hospital Univ. Clínico de Valencia
- Hospital Univ. Lozano Blesa
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Experimental arm:
Comparator arm
Arm Description
they will take 1 tablet (50 mg BIC + 200 mg FTC + 25 mg TAF), orally, once a day, from the moment of randomization.
they will take 1 tablet of 50 mg of DTG orally, once a day + 1 tablet of 300 mg of 3TC orally, once a day, from the randomization moment.
Outcomes
Primary Outcome Measures
sCD14
Changes in sCD14 concentration
Secondary Outcome Measures
Changes in PCR-us
Inflammation (IL-6 signaling pathways):
Changes in sCD163
Monocyte / macrophage activation
Changes in quinurenine / tryptophan ratio
IDO-1 induction
Changes in Dimer D
Coagulation
Changes in CD4/CD8 ratio
Inmunoactivation
Changes in CD4+
Changes in viral suppression rates
Longitudinal trajectories of plasma biomarkers
The differences in the trajectories of soluble inflammatory markers by comparing the slopes of each biomarker between treatment arms. Longitudinal changes in each biomarker will be compared using linear or non-linear mixed models with random intercepts, depending on the normality of the data.
Longitudinal trajectories of CD4/CD8 ratio
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04076423
Brief Title
A Phase IV Study to Assess the Impact of the Change of Antiretroviral Treatment From Dual Therapy to Triple Therapy on Inflammation in Patients With HIV Infection
Acronym
InSTINCT
Official Title
A Phase IV, Multicenter, Open and Randomized Study to Assess the Impact of the Change From Antiretroviral Treatment From Dual Therapy to Triple Therapy on Inflammation in Patients With Type 1 HIV Infection. InSTINCT Study
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 10, 2019 (Actual)
Primary Completion Date
June 15, 2023 (Actual)
Study Completion Date
June 15, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fundacion SEIMC-GESIDA
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
242 patients (121 patients in each of the two treatment arms) will be included with a confirmed diagnosis of HIV-1 infection and with a stable antiretroviral treatment during more than 48 weeks with dual therapy (DTG + 3TC)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Comparator: the patient will continue taking the dual therapy. Experimental: the patient Will beging to take triple therapy.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
242 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Experimental arm:
Arm Type
Experimental
Arm Description
they will take 1 tablet (50 mg BIC + 200 mg FTC + 25 mg TAF), orally, once a day, from the moment of randomization.
Arm Title
Comparator arm
Arm Type
Active Comparator
Arm Description
they will take 1 tablet of 50 mg of DTG orally, once a day + 1 tablet of 300 mg of 3TC orally, once a day, from the randomization moment.
Intervention Type
Drug
Intervention Name(s)
Dual Therapy
Intervention Description
DTG + 3TC
Intervention Type
Drug
Intervention Name(s)
Triple therapy
Intervention Description
BIC / FTC / TAF
Primary Outcome Measure Information:
Title
sCD14
Description
Changes in sCD14 concentration
Time Frame
Screening, basal, week 23, week 24, week 47, week 48, week 95 y week 96
Secondary Outcome Measure Information:
Title
Changes in PCR-us
Description
Inflammation (IL-6 signaling pathways):
Time Frame
Screening, basal, week 23, week 24, week 47, week 48, week 95 y week 96
Title
Changes in sCD163
Description
Monocyte / macrophage activation
Time Frame
Screening, basal, week 23, week 24, week 47, week 48, week 95 y week 96
Title
Changes in quinurenine / tryptophan ratio
Description
IDO-1 induction
Time Frame
Screening, basal, week 23, week 24, week 47, week 48, week 95 y week 96
Title
Changes in Dimer D
Description
Coagulation
Time Frame
Screening, basal, week 23, week 24, week 47, week 48, week 95 y week 96
Title
Changes in CD4/CD8 ratio
Description
Inmunoactivation
Time Frame
Screening, basal, week 23, week 24, week 47, week 48, week 95 y week 96
Title
Changes in CD4+
Time Frame
Throughout all the study, an average of 100 weeks
Title
Changes in viral suppression rates
Time Frame
Throughout all the study, an average of 100 weeks
Title
Longitudinal trajectories of plasma biomarkers
Description
The differences in the trajectories of soluble inflammatory markers by comparing the slopes of each biomarker between treatment arms. Longitudinal changes in each biomarker will be compared using linear or non-linear mixed models with random intercepts, depending on the normality of the data.
Time Frame
Throughout all the study, an average of 100 weeks
Title
Longitudinal trajectories of CD4/CD8 ratio
Time Frame
Throughout all the study, an average of 100 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Men and women ≥ 18 years
Confirmed and documented diagnosis of HIV-1 infection
Virological suppression of more than 48 weeks (confirmed with HIV RNA <50 copies / ml). The determination of the CV of a routine prior analysis of ≤ 12 weeks prior to signature of consent.
ART in stable dual therapy (> 48 weeks) with DTG + 3TC
Signed informed consent
Negative pregnancy test in urine or blood
Exclusion Criteria:
Inability to obtain written informed consent to participate in the study
Pregnant or breastfeeding women or those who intend to become pregnant during the study period and do not undertake to use proven contraceptive methods.
Any suspicion or confirmation of resistance to TAF, 3TC, FTC, DTG or BIC. In case of have a study of baseline resistance mutations prior to the start of ART has to rule out resistance to investigational drugs.
Patients with hypersensitivity to any excipient used with TAF, FTC, DTG or BIC
Any chronic autoimmune or inflammatory disease
Use of immunomodulatory or immunosuppressive agents, including steroids Chronic treatment with aspirin, statins and other anti-inflammatory agents
Any acute infection in the last 2 months
Estimated glomerular filtration rate (TFGe) <30 mg / ml / m2 measured by any of the formulas available. The determination of the TFGe of a previous routine analysis of ≤ 12 weeks prior to signing the consent is allowed
Contraindication for the use of TAF
Clinical condition of the patient in rapid deterioration or the investigator considers that there is no reasonable hope that the patient will finish the study
Simultaneous participation in another clinical trial or research study that requires the need of treatment with other drugs outside the study or interfere with the visits of the same.
Any situation that, in the opinion of the investigator, may interfere with the patient's ability to meet the treatment schedule and protocol evaluations
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Santiago Moreno, MD
Organizational Affiliation
Hospital Univ. Ramón y Cajal
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Sergio Serrano, MD
Organizational Affiliation
Hospital Univ. Ramón y Cajal
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital General de Alicante
City
Alicante
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joaquin Portilla, MD
Email
portilla_joa@gva.es
Facility Name
H. Clinic i Provincial
City
Barcelona
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Josep Mallolas, MD
Email
MALLOLAS@clinic.ub.es
Facility Name
Hospital de Bellvitge
City
Barcelona
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juan Tiraboschi, MD
Phone
+34 932607667
Ext
2886
Email
jmtiraboschi@bellvitgehospital.cat
Facility Name
Hospital Univ. Vall D'Hebron
City
Barcelona
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Josquín Burgos, MD
Email
jburgos@vhebron.net
Facility Name
Hospital Reina Sofia
City
Córdoba
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antonio Rivero, MD
Email
ariveror@gmail.com
Facility Name
Hospital Clínico San Carlos
City
Madrid
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vicente Estrada, MD
Email
vesda001@gmail.com
Facility Name
Hospital Fundación Jimenez Diaz
City
Madrid
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alfonso Cabello, MD
Email
ACabello@fjd.es
Facility Name
Hospital Univ. de La Princesa
City
Madrid
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ignacio De los Santos, MD
Email
isantosg@hotmail.com
Facility Name
Hospital Univ. La Paz
City
Madrid
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juan Gonzalez, MD
Phone
+34 91 727 70 99
Email
juangonzalezgar@gmail.com
Facility Name
Hospital Univ. Ramón y Cajal
City
Madrid
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Santiago Moreno, MD
Phone
+34 913369100
Email
smguillen@salud.madrid.org
Facility Name
Hospital Virgen de las Nieves
City
Malá
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juan Pasquau, MD
Phone
+34 958895414
Email
jpasquau@gmail.com
Facility Name
Hospital Regional Carlos Haya
City
Málaga
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Manuel A Castaño, MD
Email
med000849@gmail.com
Facility Name
Hospital Virgen de la Victoria
City
Málaga
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jesús Santos, MD
Email
med000854@gmail.com
Facility Name
Hospital de Santiago
City
Santiago De Compostela
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antonio Antela, MD
Email
antelacanary@gmail.com
Facility Name
Hospital Univ. Virgen del Rocio
City
Sevilla
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Luis F Lopez-Cortes, MD
Email
luisfernando@lopezcortes.net
Facility Name
Hospital Univ. Clínico de Valencia
City
Valencia
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mª José Galindo, MD
Email
galindo.pepa1@gmail.com
Facility Name
Hospital Univ. Lozano Blesa
City
Zaragoza
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mª Jose Crusells, MD
Email
pcrusells@gmail.com
12. IPD Sharing Statement
Learn more about this trial
A Phase IV Study to Assess the Impact of the Change of Antiretroviral Treatment From Dual Therapy to Triple Therapy on Inflammation in Patients With HIV Infection
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