Back to resultsEvaluation of a Simplified Strategy for the Long-term Management of HIV Infection (Simpl'HIV) (Simpl'HIV)
Primary Purpose
HIV-1-infection, Antiretroviral Therapy, Maintenance Therapy
Status
Completed
Phase
Phase 4
Locations
Switzerland
Study Type
Interventional
Intervention
Switch to DTG + FTC
Patient-centered monitoring
Sponsored by
About this trial
This is an interventional treatment trial for HIV-1-infection
Eligibility Criteria
Inclusion Criteria:
- Informed consent as documented by signature;
- Documented HIV-1 infection;
- Enrolled in the Swiss HIV Cohorte Study (SHCS) or receiving care from a medical doctor of the SHCS network;
- ≥ 18 years of age;
- HIV-RNA <50 copies/mL at screening and for at least 24 weeks before screening on effective suppressive cART, one blip with less than 200 copies/mL being allowed during this period if followed by at least 2 results < 50 copies/mL.
On standard cART at the time of inclusion, i.e.:
- 2 NRTIs + either 1 NNRTI, 1 boosted PI or 1 INSTI;
- NRTI-sparing triple ARV regimen (e.g. 1 NRTI + 1 NNRTI + 1 InSTI);
- Dual therapy with protease inhibitor.
Exclusion Criteria:
- HIV-2 infection;
Previous ART change for unsatisfactory virological response, i.e. slow initial virological suppression, incomplete suppression or rebound. Change of drug or drug class for convenience or toxic effect prevention or management is allowed.
Note: patients with documented genotype(s) presenting only a M184V mutation remain eligible;
- Creatinine clearance < 50ml/min;
- ASAT or ALAT >2.5x upper limit of the norm;
- Known hypersensitivity, intolerance or allergy to DTG or FTC;
- Known or suspected non-adherence (defined as <80% adherence, i.e. missed doses > 1x/week) to current treatment in the last 6 months;
- Concomitant use of drugs that decrease DTG blood concentrations including carbamazepine, oxcarbamazepine, phenytoin, phenobarbital, St John's wort and rifampicin;
- Women who are pregnant or breast-feeding;
a. Presence of any INSTI-resistance. Non-availability of INSTI resistance testing is NOT an exclusion criteria.
b. Non availability of previous routine resistance test, at least for reverse transcriptase and protease genes.
Note: Subjects remain eligible in the absence of any previous resistance test only if they are on their first-line antiretroviral regimen;
- Evidence of acute or chronic hepatitis B virus infection based on results of serology testing.
Sites / Locations
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Basel
- Departement of Infectious Disease, Bern University Hospital
- Infectious diseases consultation, University Hospitals of Geneva
- Infectious Diseases Service, Lausanne University Hospital
- Department of Infectious Diseases, Lugano Regional Hospital
- Division of Infectious Diseases and Hospital Epidemiology, Kantonspital St.Gallen
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
No Intervention
Experimental
Experimental
Experimental
Arm Label
Continuing cART + Standard monitoring
Continuing cART + Patient-centered monitoring
Switch to DTG+FTC + Standard monitoring
Switch to DTG+FTC + Patient-centered monitoring
Arm Description
Patients randomized to this arm will continue their current standard ART regimen (cART) and will continue a standard 3-monthly routine safety biological monitoring (including CD4 cell count, fasting lipids and glucose, renal and hepatic function tests) at their SHCS site.
Patients randomized to this arm will continue their current cART and will have immunological and safety blood examinations performed once per year and at least one options (decentralised venipuncture and blood tests, delivery of ARV drugs by mail and interview by phone or skype call) for weeks 6, 12 and 36
Patients randomized to this arm will be switched to DTG + FTC dual maintenance therapy and will have immunological and safety blood examinations performed once per year and at least one options (decentralised venipuncture and blood tests, delivery of ARV drugs by mail and interview by phone or skype call) for weeks 6, 12 and 36
Patients randomized to this arm will be switched to DTG + FTC dual maintenance therapy and will have immunological and safety blood examinations performed at screening and at week 48. In addition, patients will be ask to choose at least one of the following alternative options for weeks 6, 12 and 36: decentralised venipuncture and blood tests, delivery of ARV drugs by mail and Assessment and clinical interview by phone or skype call
Outcomes
Primary Outcome Measures
Efficacy of DTG-based maintenance therapy (< 100 copies/ml)
Proportion of patients maintaining HIV-RNA <100 copies/ml throughout 48 weeks
Costs of a patient-centered ART monitoring
Direct costs of the two study arms from the health care system perspective at week 48
Secondary Outcome Measures
Efficacy of DTG-based maintenance therapy (<50 copies/ml)
Proportion of patients maintaining HIV-RNA <50 copies/ml throughout 48 weeks
Efficacy of DTG-based therapy (<50 copies/ml) by FDA snapshot analysis
Proportion of patients with HIV-RNA < 50 cp/ml at week 48
HIV-RNA >100 copies/ml as time to loss of virological response (TLOVR)
defined as the first of the two-confirmed HIV-RNA >100 copies/ml (at least two weeks apart)
Change in CD4 cell count
from baseline to week 48
Change in HIV-DNA
from baseline to week 48
Change in lipidic profile
from baseline to week 48
Change in glucose profile
from baseline to week 48
Change in Framingham-calculated cardiovascular risk
from baseline to week 48
Change in glomerular function rate
from baseline to week 48
Proportion of patients with an adverse event
throughout week 48
Proportion of patients with a severe adverse event
throughout week 48
Proportion of patients with CNS adverse event
throughout week 48
Proportion of patients new to DTG with CNS symptoms
at 2 and 6 week
PROQOL questionnaire
from baseline to weeks 12 and 48
Patient's monitoring satisfaction for pts in the patient-centered monitoring arm
from baseline to weeks 24 and 48
Global satisfaction of the monitoring
at week 48
Proportion of patients in the patient-centered monitoring arm expressing willingness to change monitoring options
Monitoring satisfaction throughout 48 weeks
Patient's treatment satisfaction at week 48
at week 48
ARV treatment in the post study
ART decided to be used in the post study period
Study satisfaction
at week 48
Cost-effectiveness of study arms
at week 48
Change in patient weight
from baseline to week 48
Adherence questions
Patient adherence to treatment throughout 48 weeks of follow-up
Number of study-related extra clinical visits
performed outside trial scheduled throughout 48 weeks
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03160105
Brief Title
Evaluation of a Simplified Strategy for the Long-term Management of HIV Infection (Simpl'HIV)
Acronym
Simpl'HIV
Official Title
Evaluation of a Simplified Strategy for the Long-term Management of HIV Infection: a Non-inferiority, Randomized, Controlled, Open-label Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
May 19, 2017 (Actual)
Primary Completion Date
April 18, 2018 (Actual)
Study Completion Date
May 20, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Calmy Alexandra
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate whether maintenance antiretroviral therapy could be simplified to DTG + FTC dual therapy and/or patient-centered monitoring once virological suppression is achieved. Using a factorial design, the study aims to assess the efficacy of DTG + FTC dual therapy to maintain virological suppression through 48 weeks of follow-up as well as the costs of a patient-centered ART laboratory monitoring.
Detailed Description
This is a pragmatic multicentre, 2x2 factorial randomized controlled trial with 1:1:1:1 randomization to switching to DTG-based maintenance dual therapy in association with FTC or continuation of cART, and to patient-centered monitoring or continuation of standard monitoring.
Patients will be followed during 48 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV-1-infection, Antiretroviral Therapy, Maintenance Therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Factorial Assignment
Model Description
This is a pragmatic multicentre, 2x2 factorial randomized controlled trial with 1:1:1:1 randomization. A sample size of 92 patients in each group will be required to demonstrate non-inferiority with a non-inferiority (NI) margin of 12%.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
186 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Continuing cART + Standard monitoring
Arm Type
No Intervention
Arm Description
Patients randomized to this arm will continue their current standard ART regimen (cART) and will continue a standard 3-monthly routine safety biological monitoring (including CD4 cell count, fasting lipids and glucose, renal and hepatic function tests) at their SHCS site.
Arm Title
Continuing cART + Patient-centered monitoring
Arm Type
Experimental
Arm Description
Patients randomized to this arm will continue their current cART and will have immunological and safety blood examinations performed once per year and at least one options (decentralised venipuncture and blood tests, delivery of ARV drugs by mail and interview by phone or skype call) for weeks 6, 12 and 36
Arm Title
Switch to DTG+FTC + Standard monitoring
Arm Type
Experimental
Arm Description
Patients randomized to this arm will be switched to DTG + FTC dual maintenance therapy and will have immunological and safety blood examinations performed once per year and at least one options (decentralised venipuncture and blood tests, delivery of ARV drugs by mail and interview by phone or skype call) for weeks 6, 12 and 36
Arm Title
Switch to DTG+FTC + Patient-centered monitoring
Arm Type
Experimental
Arm Description
Patients randomized to this arm will be switched to DTG + FTC dual maintenance therapy and will have immunological and safety blood examinations performed at screening and at week 48. In addition, patients will be ask to choose at least one of the following alternative options for weeks 6, 12 and 36: decentralised venipuncture and blood tests, delivery of ARV drugs by mail and Assessment and clinical interview by phone or skype call
Intervention Type
Drug
Intervention Name(s)
Switch to DTG + FTC
Intervention Description
Switch from standard cART to DTG + FTC dual maintenance therapy.
Intervention Type
Other
Intervention Name(s)
Patient-centered monitoring
Intervention Description
Immunological and safety blood examinations performed only once per year at least one options (decentralised venipuncture and blood tests, delivery of ARV drugs by mail and interview by phone or skype call) for weeks 6, 12 and 36
Primary Outcome Measure Information:
Title
Efficacy of DTG-based maintenance therapy (< 100 copies/ml)
Description
Proportion of patients maintaining HIV-RNA <100 copies/ml throughout 48 weeks
Time Frame
48 weeks
Title
Costs of a patient-centered ART monitoring
Description
Direct costs of the two study arms from the health care system perspective at week 48
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
Efficacy of DTG-based maintenance therapy (<50 copies/ml)
Description
Proportion of patients maintaining HIV-RNA <50 copies/ml throughout 48 weeks
Time Frame
48 weeks
Title
Efficacy of DTG-based therapy (<50 copies/ml) by FDA snapshot analysis
Description
Proportion of patients with HIV-RNA < 50 cp/ml at week 48
Time Frame
48 weeks
Title
HIV-RNA >100 copies/ml as time to loss of virological response (TLOVR)
Description
defined as the first of the two-confirmed HIV-RNA >100 copies/ml (at least two weeks apart)
Time Frame
48 weeks
Title
Change in CD4 cell count
Description
from baseline to week 48
Time Frame
48 weeks
Title
Change in HIV-DNA
Description
from baseline to week 48
Time Frame
48 weeks
Title
Change in lipidic profile
Description
from baseline to week 48
Time Frame
48 weeks
Title
Change in glucose profile
Description
from baseline to week 48
Time Frame
48 weeks
Title
Change in Framingham-calculated cardiovascular risk
Description
from baseline to week 48
Time Frame
48 weeks
Title
Change in glomerular function rate
Description
from baseline to week 48
Time Frame
48 weeks
Title
Proportion of patients with an adverse event
Description
throughout week 48
Time Frame
48 weeks
Title
Proportion of patients with a severe adverse event
Description
throughout week 48
Time Frame
48 weeks
Title
Proportion of patients with CNS adverse event
Description
throughout week 48
Time Frame
48 weeks
Title
Proportion of patients new to DTG with CNS symptoms
Description
at 2 and 6 week
Time Frame
6 weeks
Title
PROQOL questionnaire
Description
from baseline to weeks 12 and 48
Time Frame
48 weeks
Title
Patient's monitoring satisfaction for pts in the patient-centered monitoring arm
Description
from baseline to weeks 24 and 48
Time Frame
48 weeks
Title
Global satisfaction of the monitoring
Description
at week 48
Time Frame
48 weeks
Title
Proportion of patients in the patient-centered monitoring arm expressing willingness to change monitoring options
Description
Monitoring satisfaction throughout 48 weeks
Time Frame
48 weeks
Title
Patient's treatment satisfaction at week 48
Description
at week 48
Time Frame
48 weeks
Title
ARV treatment in the post study
Description
ART decided to be used in the post study period
Time Frame
48 weeks
Title
Study satisfaction
Description
at week 48
Time Frame
48 weeks
Title
Cost-effectiveness of study arms
Description
at week 48
Time Frame
48 weeks
Title
Change in patient weight
Description
from baseline to week 48
Time Frame
48 weeks
Title
Adherence questions
Description
Patient adherence to treatment throughout 48 weeks of follow-up
Time Frame
48 weeks
Title
Number of study-related extra clinical visits
Description
performed outside trial scheduled throughout 48 weeks
Time Frame
48 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Informed consent as documented by signature;
Documented HIV-1 infection;
Enrolled in the Swiss HIV Cohorte Study (SHCS) or receiving care from a medical doctor of the SHCS network;
≥ 18 years of age;
HIV-RNA <50 copies/mL at screening and for at least 24 weeks before screening on effective suppressive cART, one blip with less than 200 copies/mL being allowed during this period if followed by at least 2 results < 50 copies/mL.
On standard cART at the time of inclusion, i.e.:
2 NRTIs + either 1 NNRTI, 1 boosted PI or 1 INSTI;
NRTI-sparing triple ARV regimen (e.g. 1 NRTI + 1 NNRTI + 1 InSTI);
Dual therapy with protease inhibitor.
Exclusion Criteria:
HIV-2 infection;
Previous ART change for unsatisfactory virological response, i.e. slow initial virological suppression, incomplete suppression or rebound. Change of drug or drug class for convenience or toxic effect prevention or management is allowed.
Note: patients with documented genotype(s) presenting only a M184V mutation remain eligible;
Creatinine clearance < 50ml/min;
ASAT or ALAT >2.5x upper limit of the norm;
Known hypersensitivity, intolerance or allergy to DTG or FTC;
Known or suspected non-adherence (defined as <80% adherence, i.e. missed doses > 1x/week) to current treatment in the last 6 months;
Concomitant use of drugs that decrease DTG blood concentrations including carbamazepine, oxcarbamazepine, phenytoin, phenobarbital, St John's wort and rifampicin;
Women who are pregnant or breast-feeding;
a. Presence of any INSTI-resistance. Non-availability of INSTI resistance testing is NOT an exclusion criteria.
b. Non availability of previous routine resistance test, at least for reverse transcriptase and protease genes.
Note: Subjects remain eligible in the absence of any previous resistance test only if they are on their first-line antiretroviral regimen;
Evidence of acute or chronic hepatitis B virus infection based on results of serology testing.
Facility Information:
Facility Name
Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Basel
City
Basel
Country
Switzerland
Facility Name
Departement of Infectious Disease, Bern University Hospital
City
Bern
Country
Switzerland
Facility Name
Infectious diseases consultation, University Hospitals of Geneva
City
Genève
Country
Switzerland
Facility Name
Infectious Diseases Service, Lausanne University Hospital
City
Lausanne
Country
Switzerland
Facility Name
Department of Infectious Diseases, Lugano Regional Hospital
City
Lugano
Country
Switzerland
Facility Name
Division of Infectious Diseases and Hospital Epidemiology, Kantonspital St.Gallen
City
St. Gallen
Country
Switzerland
Facility Name
Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich
City
Zürich
Country
Switzerland
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33170863
Citation
Sculier D, Wandeler G, Yerly S, Marinosci A, Stoeckle M, Bernasconi E, Braun DL, Vernazza P, Cavassini M, Buzzi M, Metzner KJ, Decosterd LA, Gunthard HF, Schmid P, Limacher A, Egger M, Calmy A; Swiss HIV Cohort Study (SHCS). Efficacy and safety of dolutegravir plus emtricitabine versus standard ART for the maintenance of HIV-1 suppression: 48-week results of the factorial, randomized, non-inferiority SIMPL'HIV trial. PLoS Med. 2020 Nov 10;17(11):e1003421. doi: 10.1371/journal.pmed.1003421. eCollection 2020 Nov.
Results Reference
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Evaluation of a Simplified Strategy for the Long-term Management of HIV Infection (Simpl'HIV)
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