HIV/AIDSPhase 2NCT03602690
Evaluation of Third-line cART Regimen in Cambodia (3DICAM)
A Phase 2 study testing Dolutegravir + Darunavir/ritonavir + optimized NRTI in people with HIV/AIDS, run by ANRS, Emerging Infectious Diseases at 1 site in Cambodia.
Trial summary
The study aims to evaluate the virological effectiveness of a third-line regimen combining dolutegravir (DTG), ritonavir-boosted darunavir (DRV/r) and optimized NRTI in Cambodian HIV-infected adults, who failed a protease inhibitors (PI)-based second-line regimen despite 3 months of boosted adherence counseling (BAC). Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- HIV/AIDS
- What is being tested?
- Dolutegravir + Darunavir/ritonavir + optimized NRTI
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteCambodia
- Study dates
- 4 Oct 2018to 11 Apr 2022
- 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 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Documented HIV-1 infection
- Failing a NNRTI-based first-line regimen
- Failing a PI-based second-line regimen after 3 months of adherence boosting (HIV RNA > 1000 copies/mL)
- HIV strain intermediate or fully resistant to ATV/r OR sensitive to ATV but both resistant to AZT, ABC and TDF
- For women of childbearing age: acceptance to use effective contraceptive methods
- Informed consent obtained with information sheet given and explained before the inclusion visit and the consent form signed by the participant and the parents or legal guardians for adolescents at the latest the day of the inclusion
Who cannot join
- History of antiretroviral treatment including darunavir and integrase inhibitor
- Active pregnancy < 12 weeks of amenorrhea and desire of pregnancy during the duration of the study
- Opportunistic infection in acute phase at inclusion including tuberculosis treated since less than one month and/or with no stable clinical condition
- Advanced cirrhosis (Child-Pugh score B or C)
- Creatinine clearance < 50 ml/mn
- Any concomitant medical condition that, according to the clinical site investigator would contraindicate participation in the study
- Concurrent participation in any other clinical study without written agreement of the two study teams
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Dolutegravir, Darunavir/Ritonavir and Optimized NRTI Recycling as a Third-line Antiretroviral Regimen in Cambodia
The study aims to evaluate the virological effectiveness of a third-line regimen combining dolutegravir (DTG), ritonavir-boosted darunavir (DRV/r) and optimized NRTI in Cambodian HIV-infected adults, who failed a protease inhibitors (PI)-based second-line regimen despite 3 months of boosted adherence counseling (BAC).
Read the detailed description
Each patient will be informed of the objectives and the total duration of the study as well as the benefits and risks to participate. After signature of consent form, Genotyping Resistance Test (GRT) and pre-inclusion samples will be done for all patients with HIV RNA > 1000 copies/mL after 3 months of boosted adherence counselling (BAC). After receiving results of the GRT and the pre-inclusion sample, the technical working group (TWG) of HIV national program will decide to switch the patient to third-line regimen or to continue second-line regimen with new BAC.
PI-based second-line regimen will be continue if 1/ GRT shows sensitivity to ATV 2/ GRT shows sensitivity to at least one of the 3 NRTI recommended in Cambodia (AZT, ABC and TDF). In that case, adherence counselling will be boosted according to the new national guidance and the patient will not be enrolled in the study.
In case of intermediate or fully resistance to ATV/r OR sensitivity to ATV but both resistances to AZT, ABC and TDF and after confirmation of eligibility criteria, patient could be enrolled in the study. A third-line regimen will be started including DRV/r 600/100 twice daily + DTG 50 mg once daily + 3TC 300 mg once daily +/- one fully or intermediate sensitive NRTI among TDF, ABC and AZT. The choice of the last NRTI will be discussed and decided by the TWG according to the HBsAg status, to the result of the GRT and to the medical history of the patient.
At 6 months, plasma HIV-1 RNA will be measured:
- HIV1-RNA < 40 copies/mL and no resistance to DRV at inclusion: a switch to DRV/r 800/100mg once daily will be done and adherence counseling provided to confirm the new dosing with the patient
- HIV1-RNA > 40 copies/mL and/or intermediate or fully resistance to DRV at inclusion: the same regimen will be continued and adherence counseling provided
For all patients, a new virological assessment will be done at 9 and 12 months.
DRV and DTG exposure and pharmacokinetic parameters (Cmax, Cmin and AUC) will be estimated for the 20 first enrolled patients, allowing an intra-patient comparison of the 2 dosing regimens of DRV/r for at least 15 patients.
- Conditions
- HIV/AIDS
- Being tested
- Dolutegravir + Darunavir/ritonavir + optimized NRTI
- Keywords
- Third-line regimen, Dolutegravir, Darunavir, Cambodia
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dolutegravir + Darunavir/ritonavir + optimized NRTIDrug
Dolutegravir 50mg once daily Darunavir/ritonavir 600/100 twice daily Optimized NRTI recycling with lamivudine and one other NRTI (zidovudine or tenofovir or abacavir)
| Study group | Role | What they receive |
|---|---|---|
| Dolutegravir + Darunavir/ritonavir + optimized NRTI | Experimental | All patients will receive ART regimen every day including:
Dolutegravir 50mg once daily Darunavir/ritonavir 600/100 twice daily Optimized NRTI recycling with lamivudine and one other NRTI (zidovudine or tenofovir or abacavir) Receives: Drug: Dolutegravir + Darunavir/ritonavir + optimized NRTI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Virological effectiveness at 6 months
Proportion of patients with plasma HIV-1 RNA < 40 copies/mL by FDA Snapshot analysis
Measured: Month 6
Secondary outcomes (6)
Virological effectiveness at 12 months
Proportion of patients with plasma HIV-1 RNA < 40 copies/mL by FDA Snapshot analysis at 12 months
Measured: Month 12
Incidence of adverse events (safety)
Incidence of grade 3-4 adverse events (ANRS grading table)
Measured: Month 12
Tolerance
Proportion of patients with permanent study treatment discontinuation during the first year
Measured: Month 12
Adherence to treatment strategy
Proportion of patients with adherence > 90%
Measured: Month 12
Plasmatic drug concentrations
Plasmatic dolutegravir concentrations
Measured: Month 1
Plasmatic drug concentrations
Plasmatic darunavir concentrations
Measured: Month 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2018
- Study start4 Oct 2018
- Primary completion11 Apr 2022 (estimated)
- Study completion11 Apr 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV/AIDSStudies of the same condition, open and under way.
- More trials run by ANRS, Emerging Infectious DiseasesThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ANRS, Emerging Infectious Diseases
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03602690
- Sponsor's protocol ID
- ANRS 12374 3DICAM
- Status last verified
- Aug 2021
- First submitted
- 6 Jul 2018
- Last updated
- 26 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dolutegravir, Darunavir/Ritonavir and Optimized NRTI Recycling as a Third-line Antiretroviral Regimen in Cambodia
- ClinicalTrials.gov ID
- NCT03602690
- Acronym / sponsor ID
- ANRS 12374 3DICAM
- Conditions
- HIV/AIDS
- Keywords
- Third-line regimen, Dolutegravir, Darunavir, Cambodia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- ANRS, Emerging Infectious DiseasesOther government
- Study start
- 4 Oct 2018 (actual)
- Primary completion
- 11 Apr 2022 (estimated)
- Study completion
- 11 Apr 2022 (estimated)
- First posted
- 27 Jul 2018 (actual)
- 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.
The study aims to evaluate the virological effectiveness of a third-line regimen combining dolutegravir (DTG), ritonavir-boosted darunavir (DRV/r) and optimized NRTI in Cambodian HIV-infected adults, who failed a protease inhibitors (PI)-based second-line regimen despite 3 months of boosted adherence counseling (BAC).
Detailed description
Each patient will be informed of the objectives and the total duration of the study as well as the benefits and risks to participate. After signature of consent form, Genotyping Resistance Test (GRT) and pre-inclusion samples will be done for all patients with HIV RNA > 1000 copies/mL after 3 months of boosted adherence counselling (BAC). After receiving results of the GRT and the pre-inclusion sample, the technical working group (TWG) of HIV national program will decide to switch the patient to third-line regimen or to continue second-line regimen with new BAC.
PI-based second-line regimen will be continue if 1/ GRT shows sensitivity to ATV 2/ GRT shows sensitivity to at least one of the 3 NRTI recommended in Cambodia (AZT, ABC and TDF). In that case, adherence counselling will be boosted according to the new national guidance and the patient will not be enrolled in the study.
In case of intermediate or fully resistance to ATV/r OR sensitivity to ATV but both resistances to AZT, ABC and TDF and after confirmation of eligibility criteria, patient could be enrolled in the study. A third-line regimen will be started including DRV/r 600/100 twice daily + DTG 50 mg once daily + 3TC 300 mg once daily +/- one fully or intermediate sensitive NRTI among TDF, ABC and AZT. The choice of the last NRTI will be discussed and decided by the TWG according to the HBsAg status, to the result of the GRT and to the medical history of the patient.
At 6 months, plasma HIV-1 RNA will be measured:
- HIV1-RNA < 40 copies/mL and no resistance to DRV at inclusion: a switch to DRV/r 800/100mg once daily will be done and adherence counseling provided to confirm the new dosing with the patient
- HIV1-RNA > 40 copies/mL and/or intermediate or fully resistance to DRV at inclusion: the same regimen will be continued and adherence counseling provided
For all patients, a new virological assessment will be done at 9 and 12 months.
DRV and DTG exposure and pharmacokinetic parameters (Cmax, Cmin and AUC) will be estimated for the 20 first enrolled patients, allowing an intra-patient comparison of the 2 dosing regimens of DRV/r for at least 15 patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dolutegravir + Darunavir/ritonavir + optimized NRTI | Experimental | Drug: Dolutegravir + Darunavir/ritonavir + optimized NRTIAll patients will receive ART regimen every day including: Dolutegravir 50mg once daily Darunavir/ritonavir 600/100 twice daily Optimized NRTI recycling with lamivudine and one other NRTI (zidovudine or tenofovir or abacavir) |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Documented HIV-1 infection
- Failing a NNRTI-based first-line regimen
- Failing a PI-based second-line regimen after 3 months of adherence boosting (HIV RNA > 1000 copies/mL)
- HIV strain intermediate or fully resistant to ATV/r OR sensitive to ATV but both resistant to AZT, ABC and TDF
- For women of childbearing age: acceptance to use effective contraceptive methods
Key exclusion criteria (7 listed)
- History of antiretroviral treatment including darunavir and integrase inhibitor
- Active pregnancy < 12 weeks of amenorrhea and desire of pregnancy during the duration of the study
- Opportunistic infection in acute phase at inclusion including tuberculosis treated since less than one month and/or with no stable clinical condition
- Advanced cirrhosis (Child-Pugh score B or C)
- Creatinine clearance < 50 ml/mn
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 |
|---|---|---|
| Dolutegravir + Darunavir/ritonavir + optimized NRTIDolutegravir 50mg once daily Darunavir/ritonavir 600/100 twice daily Optimized NRTI recycling with lamivudine and one other NRTI (zidovudine or tenofovir or abacavir) | Drug | Dolutegravir + Darunavir/ritonavir + optimized NRTI |
Primary outcome
Virological effectiveness at 6 months
Time frame: Month 6
Proportion of patients with plasma HIV-1 RNA < 40 copies/mL by FDA Snapshot analysis
6 secondary outcomes
Virological effectiveness at 12 months
Time frame: Month 12
Incidence of adverse events (safety)
Time frame: Month 12
Tolerance
Time frame: Month 12
Adherence to treatment strategy
Time frame: Month 12
Plasmatic drug concentrations
Time frame: Month 1
Plasmatic drug concentrations
Time frame: Month 1
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2021.
- Individual participant dataSharing planned: No
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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.
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 + Darunavir/ritonavir + optimized NRTI in people with HIV/AIDS, run by ANRS, Emerging Infectious Diseases at 1 site in Cambodia.
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 6 inclusion and 7 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 26 Aug 2021. 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 Cambodia. 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?
Contact Phearavin Pheng (+85512578726, phearavinpheng@uhs.edu.kh), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Virological effectiveness at 6 months (time frame: Month 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Aug 2021.