MonotherapyPhase 2NCT02551523
Early Simplified: A Trial to Compare the Efficacy of Standard of Care Combination Antiretroviral Therapy With a Simplified Dolutegravir Monotherapy in Patients With a Primary HIV-1 Infection
A Phase 2 study testing Dolutegravir in people with Monotherapy and Dolutegravir, run by University of Zurich at 1 site in Switzerland.
Trial summary
Long term toxicity of combination antiretroviral therapy (cART) is a substantial contributor to morbidity and mortality in chronically infected HIV positive individuals. To date it is still debated, whether long term nucleoside reverse transcriptase inhibitors (NRTI's) -sparing regimens are practicable or even… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Monotherapy, Dolutegravir, Primary HIV Infection
- What is being tested?
- Dolutegravir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 101 participants
- Where
- 1 siteSwitzerland
- Study dates
- Nov 2016to Feb 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Informed Consent as documented by signature,
- All patients ≥18 years with a documented primary HIV-infection undergoing standard of care cART (i.e., one active drug from the class of either the PIs, or the NNRTIs, or the INSTIs, in combination with two active drugs from the class of NRTIs) with no previous structured treatment interruption and with a suppressed viral load (defined as 50 copies/ml) during the previous 48 weeks,
- Participant of the Swiss HIV Cohort Study
Who cannot join
- Patients not willing to sign the informed consent form,
- Presence of ≥1 major integrase inhibitor resistance associated mutation according to the Sanford algorithm1,
- History of ≥2 consecutive plasma viremia levels >400 copies/ml at least two weeks apart,
- Ongoing (i.e., replicating) hepatitis B virus infection,
- Hemoglobin < 10 g/dl (men) and < 9 g/dl (women) at the time of enrolment,
- Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product,
Show all 15Show fewer
- Women who are pregnant or breast feeding,
- Intention to become pregnant during the course of the study,
- Lack of safe contraception,
- Other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, etc.),
- Known or suspected non-compliance, drug or alcohol abuse,
- Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
- Participation in another study with investigational drug within the 30 days preceding and during the present study,
- Previous enrolment into the current study,
- Enrolment of the investigator, his/her family members, employees and other dependent persons.
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
University Hospital Zurich, University of Zurich
Zurich, 8091
About this study
Official title: A Prospective, Randomised, Controlled, Open-label, Non-inferiority Trial to Compare the Efficacy of Standard of Care Combination Antiretroviral Therapy With a Simplified Dolutegravir Monotherapy in Patients With a Primary HIV-1 Infection Under Suppressive Early Standard of Care Antiretroviral Therapy
Long term toxicity of combination antiretroviral therapy (cART) is a substantial contributor to morbidity and mortality in chronically infected HIV positive individuals. To date it is still debated, whether long term nucleoside reverse transcriptase inhibitors (NRTI's) -sparing regimens are practicable or even superior compared to standard of care cART in terms of efficacy, safety and tolerability. In addition, data about efficacy of integrase inhibitor (INSTI) based monotherapy is lacking. We aim at investigating the efficacy of standard of care combination antiretroviral therapy with a simplified dolutegravir monotherapy in patients with a primary HIV-1 infection under suppressive early standard of care antiretroviral therapy. Briefly, hundred-thirty-eight patients with a documented primary HIV1- infection (PHI) will be recruited from the Zurich Primary HIV-1 Infection Study (ZHPI), which is an open label, non-randomized, observational, single-center study (http://clinicaltrials.gov, ID 5 NCT00537966). All subjects formerly underwent early cART consisting of either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a INSTI in combination with two NRTIs at the time point of enrolment in the ZPHI and must be under a fully suppressive ART (i.e., <50 copies/ml) for at least 48 weeks at the time point of randomisation. The primary end point is the proportion of individuals with a viral failure at week 48 or before.
- Conditions
- Monotherapy, Dolutegravir, Primary HIV Infection, Treatment Efficacy
- Being tested
- Dolutegravir, Standard of care combinational antiretroviral therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DolutegravirDrug
92 patients will be simplified to once daily dolutegravir monotherapy
Standard of care combinational antiretroviral therapyDrug
| Study group | Role | What they receive |
|---|---|---|
| Dolutegravir monotherapy | Experimental | 92 patients will be simplified to once daily dolutegravir monotherapy. Receives: Drug: Dolutegravir |
| Standard of care combination antiretroviral therapy | Active comparator | 46 patients will go on with standard of care combination antiretroviral therapy consisting of either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor or a integrase inhibitor in combination with two nucleoside reverse transcriptase inhibitors. Receives: Drug: Standard of care combinational antiretroviral therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of individuals with a viral failure [defined as ≥2 plasma viremia levels >50copies/ml at least two weeks apart] at week 48 or before.
The study seeks primarily to determine the efficacy (i.e., proportion of patients with a viral failure [defined as ≥2 plasma viremia levels >50copies/ml at least two weeks apart] at week 48 or before) of a simplified monotherapy (i.e., DTG) compared to a standard of care HIV triple-therapy in patients with a PHI treated with early ART under long term suppressive ART for at least 48 weeks.
Measured: 48 weeks
Secondary outcomes (14)
Quantification of latent HIV-1 reservoir by measurement of proviral DNA and cell-associated RNA at baseline (time point of randomization), and at week 48
Measured: Week48
Proportion of individuals with a CSF HIV-1 RNA <50copies/ml in the CSF at week 48 after treatment simplification.
Measured: Week 48
Proportion of patients with an adverse event at week 48.
Measured: Week 48
Proportion of patients with a severe adverse event at week 48.
Measured: Week 48
Time to viral failure (defined as ≥2 plasma viremia levels >50copies/ml at least two weeks apart) at week 48.
Measured: Week 48
Proportion of individuals with blips (defined as one viral load >50 and <400 copies/ml with a next viral load <50 copies/ml) at week 48.
Measured: Week 48
Change from baseline CD4+ cell count from baseline at week 48.
Measured: Week 48
Proportion of individuals with new onset of proximal tubular renal dysfunction at week 48.
Measured: Week 48
Creatinine clearance change from baseline at week 48.
Measured: Week 48
Lipidic profile changes from baseline at week 48.
Measured: Week 48
Proportion of individuals developing a new CDC-event at week 48.
Measured: Week 48
Proportion of individuals withdrawing consent at week 48.
Measured: Week 48
Proportion of individuals being lost to follow-up at week 48.
Measured: Week 48
Proportion of individuals switching assigned treatment for any cause at week 48.
Measured: Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2015 (estimated)
- Study startNov 2016
- Primary completionOct 2018 (estimated)
- Study completionFeb 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MonotherapyStudies of the same condition, open and under way.
- More trials run by University of ZurichThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dominique L Braun, MD, Principal investigator, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02551523
- Sponsor's protocol ID
- KEK-ZH-Nr. 2015-0288
- Status last verified
- Oct 2018
- First submitted
- 15 Sep 2015
- Last updated
- 12 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Braun DL, Turk T, Tschumi F, Grube C, Hampel B, Depmeier C, Schreiber PW, Brugger SD, Greiner M, Steffens D, De Torrente-Bayard C, Courlet P, Neumann K, Kuster H, Flepp M, Bertisch B, Decosterd L, Boni J, Metzner KJ, Kouyos RD, Gunthard HF. Noninferiority of Simplified Dolutegravir Monotherapy Compared to Continued Combination Antiretroviral Therapy That Was Initiated During Primary Human Immunodeficiency Virus Infection: A Randomized, Controlled, Multisite, Open-label, Noninferiority Trial. Clin Infect Dis. 2019 Oct 15;69(9):1489-1497. doi: 10.1093/cid/ciy1131.
PubMed 30601950
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomised, Controlled, Open-label, Non-inferiority Trial to Compare the Efficacy of Standard of Care Combination Antiretroviral Therapy With a Simplified Dolutegravir Monotherapy in Patients With a Primary HIV-1 Infection Under Suppressive Early Standard of Care Antiretroviral Therapy
- ClinicalTrials.gov ID
- NCT02551523
- Acronym / sponsor ID
- KEK-ZH-Nr. 2015-0288
- Conditions
- Monotherapy, Dolutegravir, Primary HIV Infection, Treatment Efficacy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 101 participants (actual)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Study start
- Nov 2016
- Primary completion
- Oct 2018 (estimated)
- Study completion
- Feb 2021 (estimated)
- First posted
- 16 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Long term toxicity of combination antiretroviral therapy (cART) is a substantial contributor to morbidity and mortality in chronically infected HIV positive individuals. To date it is still debated, whether long term nucleoside reverse transcriptase inhibitors (NRTI's) -sparing regimens are practicable or even superior compared to standard of care cART in terms of efficacy, safety and tolerability. In addition, data about efficacy of integrase inhibitor (INSTI) based monotherapy is lacking. We aim at investigating the efficacy of standard of care combination antiretroviral therapy with a simplified dolutegravir monotherapy in patients with a primary HIV-1 infection under suppressive early standard of care antiretroviral therapy. Briefly, hundred-thirty-eight patients with a documented primary HIV1- infection (PHI) will be recruited from the Zurich Primary HIV-1 Infection Study (ZHPI), which is an open label, non-randomized, observational, single-center study (http://clinicaltrials.gov, ID 5 NCT00537966). All subjects formerly underwent early cART consisting of either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a INSTI in combination with two NRTIs at the time point of enrolment in the ZPHI and must be under a fully suppressive ART (i.e., <50 copies/ml) for at least 48 weeks at the time point of randomisation. The primary end point is the proportion of individuals with a viral failure at week 48 or before.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dolutegravir monotherapy | Experimental | Drug: Dolutegravir92 patients will be simplified to once daily dolutegravir monotherapy. |
| Standard of care combination antiretroviral therapy | Active comparator | Drug: Standard of care combinational antiretroviral therapy46 patients will go on with standard of care combination antiretroviral therapy consisting of either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor or a integrase inhibitor in combination with two nucleoside reverse transcriptase inhibitors. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Informed Consent as documented by signature,
- All patients ≥18 years with a documented primary HIV-infection undergoing standard of care cART (i.e., one active drug from the class of either the PIs, or the NNRTIs, or the INSTIs, in combination with two active drugs from the class of NRTIs) with no previous structured treatment interruption and with a suppressed viral load (defined as 50 copies/ml) during the previous 48 weeks,
- Participant of the Swiss HIV Cohort Study
Key exclusion criteria (15 listed)
- Patients not willing to sign the informed consent form,
- Presence of ≥1 major integrase inhibitor resistance associated mutation according to the Sanford algorithm1,
- History of ≥2 consecutive plasma viremia levels >400 copies/ml at least two weeks apart,
- Ongoing (i.e., replicating) hepatitis B virus infection,
- Hemoglobin < 10 g/dl (men) and < 9 g/dl (women) at the time of enrolment,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dolutegravir92 patients will be simplified to once daily dolutegravir monotherapy | Drug | Dolutegravir monotherapy |
| Standard of care combinational antiretroviral therapy | Drug | Standard of care combination antiretroviral therapy |
Primary outcome
Proportion of individuals with a viral failure [defined as ≥2 plasma viremia levels >50copies/ml at least two weeks apart] at week 48 or before.
Time frame: 48 weeks
The study seeks primarily to determine the efficacy (i.e., proportion of patients with a viral failure [defined as ≥2 plasma viremia levels >50copies/ml at least two weeks apart] at week 48 or before) of a simplified monotherapy (i.e., DTG) compared to a standard of care HIV triple-therapy in patients with a PHI treated with early ART under long term suppressive ART for at least 48 weeks.
14 secondary outcomes
Quantification of latent HIV-1 reservoir by measurement of proviral DNA and cell-associated RNA at baseline (time point of randomization), and at week 48
Time frame: Week48
Proportion of individuals with a CSF HIV-1 RNA <50copies/ml in the CSF at week 48 after treatment simplification.
Time frame: Week 48
Proportion of patients with an adverse event at week 48.
Time frame: Week 48
Proportion of patients with a severe adverse event at week 48.
Time frame: Week 48
Time to viral failure (defined as ≥2 plasma viremia levels >50copies/ml at least two weeks apart) at week 48.
Time frame: Week 48
Proportion of individuals with blips (defined as one viral load >50 and <400 copies/ml with a next viral load <50 copies/ml) at week 48.
Time frame: Week 48
Change from baseline CD4+ cell count from baseline at week 48.
Time frame: Week 48
Proportion of individuals with new onset of proximal tubular renal dysfunction at week 48.
Time frame: Week 48
Creatinine clearance change from baseline at week 48.
Time frame: Week 48
Lipidic profile changes from baseline at week 48.
Time frame: Week 48
Proportion of individuals developing a new CDC-event at week 48.
Time frame: Week 48
Proportion of individuals withdrawing consent at week 48.
Time frame: Week 48
Proportion of individuals being lost to follow-up at week 48.
Time frame: Week 48
Proportion of individuals switching assigned treatment for any cause at week 48.
Time frame: Week 48
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2018.
- Derived from this study: PubMed 30601950Braun DL, Turk T, Tschumi F, Grube C, Hampel B, Depmeier C, Schreiber PW, Brugger SD, Greiner M, Steffens D, De Torrente-Bayard C, Courlet P, Neumann K, Kuster H, Flepp M, Bertisch B, Decosterd L, Boni J, Metzner KJ, Kouyos RD, Gunthard HF. Noninferiority of Simplified Dolutegravir Monotherapy Compared to Continued Combination Antiretroviral Therapy That Was Initiated During Primary Human Immunodeficiency Virus Infection: A Randomized, Controlled, Multisite, Open-label, Noninferiority Trial. Clin Infect Dis. 2019 Oct 15;69(9):1489-1497. doi: 10.1093/cid/ciy1131.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dominique L Braun, MD principal investigator
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dolutegravir in people with Monotherapy and Dolutegravir, run by University of Zurich at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of individuals with a viral failure [defined as ≥2 plasma viremia levels >50copies/ml at least two weeks apart] at week 48 or before. (time frame: 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02551523, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2018.