HIV-infection/AidsPhase 4i2-D²EFTNCT04183738
Inflammation and Co-Infections in D²EFT
A Phase 4 study testing NRTIs, Darunavir and Ritonavir in people with HIV-infection/Aids and Human Herpesvirus 4 Infections, run by Kirby Institute.
Trial summary
i2-D²EFT substudy is an observational cohort nested within the parent D²EFT study (NCT03017872). D²EFT goal is to compare the standard of care second-line antiretroviral therapy in people living with HIV whose first-line non nucleoside reverse transcriptase-based regimen failed, to two simpler regimens. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV-infection/Aids, Human Herpesvirus 4 Infections, Cytomegalovirus Infections
- What is being tested?
- NRTIs, Darunavir and Ritonavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Feb 2021to 19 Dec 2022
- Phase
- Phase 4
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Fulfil the eligibility criteria for D²EFT randomisation;
- Being able to give a written informed consent for the i2-D²EFT sub-study.
Who cannot join
- Unwilling to comply with the i2-D²EFT protocol requirements.
About this study
Official title: The Impact of Co-infections on Inflammation in Patients Commencing Second-line Antiretroviral Therapy. A Sub-study of D²EFT (Dolutegravir and Darunavir Evaluation in Adults Failing Therapy)
i2-D²EFT substudy is an observational cohort nested within the parent D²EFT study (NCT03017872). D²EFT goal is to compare the standard of care second-line antiretroviral therapy in people living with HIV whose first-line non nucleoside reverse transcriptase-based regimen failed, to two simpler regimens. Approximately 1,000 participants will be enrolled in D²EFT.
Commencing a second-line ART is an important moment when the level of inflammation in participants may be elevated due to first-line ART failure; this level of inflammation should then decrease with the commencement of a new second-line treatment and would be expected to normalise by 48 weeks of second-line treatment, if successful.
The investigators propose to study other factors which can influence the decrease of inflammation. The investigators hypothesise that co-infections may play a role in persistent inflammation. The key-infections of interest will be common frequent infections encounter throughout the world: Human Herpes virus 8, Epstein-Barr virus, Cytomegalovirus and Human papillomavirus, tuberculosis, malaria and other key opportunistic infections. Possible changes of level of inflammation (using the serum level of Interleukin 6) in approximately 200 participants of the D²EFT study will be investigated and measured. The hypothesis is that the presence of other infections than HIV may influence the level of inflammation in participants in therapeutic success.
Read the detailed description
i2-D²EFT substudy an observational cohort nested within the parent open label phase III/IV randomised controlled trial of simplified second-line therapy, D²EFT (NCT03017872). Participants consenting to D²EFT study will be randomised within the three arms: either ritonavir-boosted darunavir plus two nucleosides or dolutegravir plus two predetermined nucleosides (tenofovir disoproxil fumarate plus lamivudine or emtricitabine) or ritonavir-boosted darunavir plus dolutegravir. Enrolment into the i2-D²EFT substudy is voluntary and optional for participants in D²EFT. Parameters relevant to i2-D²EFT substudy including demographics, arm of randomised ART, HIV history, physical examination, immunological and virological results, episodes of co-infections and adverse events due to any infection or malignancies at required time points will be collected as part of D²EFT study. Substudy specific assessments performed at baseline and at weeks 48 include sample collection for IL-6 dosage plus EBV/CMV/HHV8 testing, and optional anal/cervical HPV screening.
- Conditions
- HIV-infection/Aids, Human Herpesvirus 4 Infections, Cytomegalovirus Infections, Human Herpesvirus 8 Infection, Human Papilloma Virus
- Being tested
- NRTIs, Darunavir, Ritonavir, Dolutegravir
- Keywords
- HIV, IL-6, EBV, CMV, HHV8, HPV, inflammation, co-infections, opportunistic infections, AIDS and non-AIDS defining cancers
- Medical subject headings
- Acquired Immunodeficiency Syndrome, Epstein-Barr Virus Infections, Cytomegalovirus Infections, Inflammation, Coinfection, Opportunistic Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NRTIsDrug
Also called Nucleoside/Nucleotide Reverse Transcription Inhibitors
In SOC arm, choice of NRTIs determined by clinician, guided by either genotypic resistance testing or use of a protocol-specified algorithm for N(t)RTI selection.
In D2N arm, NRTIs are predetermined.
DarunavirDrug
Also called Prezista
800mg tablet by mouth once daily for 96 weeks.
RitonavirDrug
Also called Norvir
100mg tablet by mouth once daily for 96 weeks.
DolutegravirDrug
Also called Tivicay
50mg tablet by mouth once daily for 96 weeks.
| Study group | Role | What they receive |
|---|---|---|
| SOC | Active comparator | darunavir/ritonavir 800/100mg + 2 NRTIs po od Receives: Drug: NRTIs; Drug: Darunavir; Drug: Ritonavir |
| DOL | Experimental | darunavir/ritonavir 800/100mg + dolutegravir 50mg po od Receives: Drug: Darunavir; Drug: Ritonavir; Drug: Dolutegravir |
| D2N | Experimental | dolutegravir 50mg + tenofovir + emtricitabine or lamivudine po od Receives: Drug: NRTIs; Drug: Dolutegravir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in IL-6 level at week 48
To compare the change of a biomarker of inflammation (IL-6) in participants who achieve HIV virological suppression (defined as peripheral blood viral load below 50 copies/mm3 at week 48) across the three study arms according to the presence (or not) of active key-co-infections (HHV8, EBV, CMV, HPV) at baseline and week 48, and the occurrence (or not) within these 48 weeks of any infection (co-infections or opportunistic infections).
Measured: At week 0 and week 48
Change from baseline of presence/absence of active key co-infections at week 48
Active key-co-infections (HHV8, EBV, CMV, HPV) at baseline and week 48, and the occurrence (or not) within these 48 weeks of any infection (co-infections or opportunistic infections).
Measured: At week 0 and week 48
Secondary outcomes (3)
Prevalence of HHV8, EBV and CMV and of cervical and anal HPV
To describe the prevalence of HHV8, EBV and CMV (defined by serological assays) and of cervical and anal HPV (defined by tissue HPV deoxyribonucleic acid (DNA) detection) at baseline, in the D2EFT cohort, by geographic region, route of HIV transmission, and other demographic and disease variables.
Measured: At week 0
Occurrence of active HHV8, EBV and CMV
To compare the occurrence of active HHV8, EBV and CMV (defined by a detectable peripheral blood viral load) in participants with and without HIV virological suppression at 48 weeks, across the three arms of D²EFT.
Measured: At week 48
Change from baseline in rates of detection of cervical and anal HPV infection at week 48
To compare rates of detection of cervical and anal HPV infection (defined by tissue HPV DNA detection) between baseline and week 48 in participants with and without HIV virological suppression at 48 weeks across the three arms of D²EFT.
Measured: At week 0 and week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2019
- Study start1 Feb 2021 (estimated)
- Primary completion19 Dec 2022 (estimated)
- Study completion19 Dec 2022 (estimated)
Why it stopped: In the context of COVID-19 pandemic.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV-infection/AidsStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Observational cohort nested within the parent open label phase III/IV randomised controlled trial of simplified second-line therapy, D²EFT.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kirby Institute
- Sponsor type
- Other government
- Collaborators
- Frederick National Laboratory for Cancer Research, UNITAID, National Institute of Allergy and Infectious Diseases (NIAID), ViiV Healthcare, Janssen Pharmaceutica
- Responsible party
- Sponsor
- Investigators
- Mark Polizzotto, MD, PhD, Principal investigator, Kirby Institute, UNSW Sydney, Australia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04183738
- Sponsor's protocol ID
- 2019-10-i2-DEFT
- Other IDs
- 18Q065
- Acronym
- i2-D²EFT
- Status last verified
- Nov 2020
- First submitted
- 28 Nov 2019
- Last updated
- 10 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- 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 10 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Co-infections on Inflammation in Patients Commencing Second-line Antiretroviral Therapy. A Sub-study of D²EFT (Dolutegravir and Darunavir Evaluation in Adults Failing Therapy)
- ClinicalTrials.gov ID
- NCT04183738
- Acronym / sponsor ID
- i2-D²EFT / 2019-10-i2-DEFT
- Conditions
- HIV-infection/Aids, Human Herpesvirus 4 Infections, Cytomegalovirus Infections, Human Herpesvirus 8 Infection, Human Papilloma Virus
- Keywords
- HIV, IL-6, EBV, CMV, HHV8, HPV, inflammation, co-infections
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: In the context of COVID-19 pandemic.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Kirby InstituteOther government
- Collaborators
- Frederick National Laboratory for Cancer Research, UNITAID, National Institute of Allergy and Infectious Diseases (NIAID), ViiV Healthcare, Janssen Pharmaceutica
- Study start
- 1 Feb 2021 (estimated)
- Primary completion
- 19 Dec 2022 (estimated)
- Study completion
- 19 Dec 2022 (estimated)
- First posted
- 3 Dec 2019 (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.
i2-D²EFT substudy is an observational cohort nested within the parent D²EFT study (NCT03017872). D²EFT goal is to compare the standard of care second-line antiretroviral therapy in people living with HIV whose first-line non nucleoside reverse transcriptase-based regimen failed, to two simpler regimens. Approximately 1,000 participants will be enrolled in D²EFT.
Commencing a second-line ART is an important moment when the level of inflammation in participants may be elevated due to first-line ART failure; this level of inflammation should then decrease with the commencement of a new second-line treatment and would be expected to normalise by 48 weeks of second-line treatment, if successful.
The investigators propose to study other factors which can influence the decrease of inflammation. The investigators hypothesise that co-infections may play a role in persistent inflammation. The key-infections of interest will be common frequent infections encounter throughout the world: Human Herpes virus 8, Epstein-Barr virus, Cytomegalovirus and Human papillomavirus, tuberculosis, malaria and other key opportunistic infections. Possible changes of level of inflammation (using the serum level of Interleukin 6) in approximately 200 participants of the D²EFT study will be investigated and measured. The hypothesis is that the presence of other infections than HIV may influence the level of inflammation in participants in therapeutic success.
Detailed description
i2-D²EFT substudy an observational cohort nested within the parent open label phase III/IV randomised controlled trial of simplified second-line therapy, D²EFT (NCT03017872). Participants consenting to D²EFT study will be randomised within the three arms: either ritonavir-boosted darunavir plus two nucleosides or dolutegravir plus two predetermined nucleosides (tenofovir disoproxil fumarate plus lamivudine or emtricitabine) or ritonavir-boosted darunavir plus dolutegravir. Enrolment into the i2-D²EFT substudy is voluntary and optional for participants in D²EFT. Parameters relevant to i2-D²EFT substudy including demographics, arm of randomised ART, HIV history, physical examination, immunological and virological results, episodes of co-infections and adverse events due to any infection or malignancies at required time points will be collected as part of D²EFT study. Substudy specific assessments performed at baseline and at weeks 48 include sample collection for IL-6 dosage plus EBV/CMV/HHV8 testing, and optional anal/cervical HPV screening.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Observational cohort nested within the parent open label phase III/IV randomised controlled trial of simplified second-line therapy, D²EFT.
| Arm | Type | Receives |
|---|---|---|
| SOC | Active comparator | Drug: NRTIs, Drug: Darunavir, Drug: Ritonavirdarunavir/ritonavir 800/100mg + 2 NRTIs po od |
| DOL | Experimental | Drug: Darunavir, Drug: Ritonavir, Drug: Dolutegravirdarunavir/ritonavir 800/100mg + dolutegravir 50mg po od |
| D2N | Experimental | Drug: NRTIs, Drug: Dolutegravirdolutegravir 50mg + tenofovir + emtricitabine or lamivudine po od |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Fulfil the eligibility criteria for D²EFT randomisation;
- Being able to give a written informed consent for the i2-D²EFT sub-study.
Key exclusion criteria (1 listed)
- Unwilling to comply with the i2-D²EFT protocol requirements.
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 |
|---|---|---|
| NRTIsAlso: Nucleoside/Nucleotide Reverse Transcription InhibitorsIn SOC arm, choice of NRTIs determined by clinician, guided by either genotypic resistance testing or use of a protocol-specified algorithm for N(t)RTI selection. In D2N arm, NRTIs are predetermined. | Drug | D2N, SOC |
| DarunavirAlso: Prezista800mg tablet by mouth once daily for 96 weeks. | Drug | DOL, SOC |
| RitonavirAlso: Norvir100mg tablet by mouth once daily for 96 weeks. | Drug | DOL, SOC |
| DolutegravirAlso: Tivicay50mg tablet by mouth once daily for 96 weeks. | Drug | D2N, DOL |
Primary outcome
Change from baseline in IL-6 level at week 48
Time frame: At week 0 and week 48
To compare the change of a biomarker of inflammation (IL-6) in participants who achieve HIV virological suppression (defined as peripheral blood viral load below 50 copies/mm3 at week 48) across the three study arms according to the presence (or not) of active key-co-infections (HHV8, EBV, CMV, HPV) at baseline and week 48, and the occurrence (or not) within these 48 weeks of any infection (co-infections or opportunistic infections).
Change from baseline of presence/absence of active key co-infections at week 48
Time frame: At week 0 and week 48
Active key-co-infections (HHV8, EBV, CMV, HPV) at baseline and week 48, and the occurrence (or not) within these 48 weeks of any infection (co-infections or opportunistic infections).
3 secondary outcomes
Prevalence of HHV8, EBV and CMV and of cervical and anal HPV
Time frame: At week 0
Occurrence of active HHV8, EBV and CMV
Time frame: At week 48
Change from baseline in rates of detection of cervical and anal HPV infection at week 48
Time frame: At week 0 and week 48
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2020.
- 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.
Mark Polizzotto, MD, PhD principal investigator
Kirby Institute, UNSW Sydney, Australia
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing NRTIs, Darunavir and Ritonavir in people with HIV-infection/Aids and Human Herpesvirus 4 Infections, run by Kirby Institute.
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 2 inclusion and 1 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: withdrawn, as of the sponsor's last update on 10 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Change from baseline in IL-6 level at week 48 (time frame: At week 0 and week 48). The study lists 2 primary outcomes in all. 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 10 Nov 2020.