Dolutegravir and Darunavir Evaluation in Adults Failing Therapy (D²EFT)
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ClinicalTrials.gov Identifier: NCT03017872 |
Recruitment Status
:
Recruiting
First Posted
: January 11, 2017
Last Update Posted
: January 12, 2018
|
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
HIV Infections | Drug: N(t)RTIs Drug: Dolutegravir Drug: Darunavir Drug: Ritonavir | Phase 4 |
Consenting participants will be screened and within 45 days randomly allocated to receive either dolutegravir and darunavir/ritonavir or the SOC regimen. Participants will be seen four weeks after their randomisation (week 0) visit and then at weeks 24, 48 and 96. Consenting participants will have storage samples collected and cryopreserved at their week 0, 48 & 96 visits. This repository will be used in future for central baseline resistance testing, pharmacogenomic testing (separate consent required) and has inherent value for later studies of HIV pathogenesis. A 1-time PK sample will be collected at week four for future testing and any participants failing therapy at 24 weeks will have a plasma sample stored for future genotypic resistance testing.
A number of secondary outcomes will be considered in order to compare the performance of the two study treatment regimens. Secondary analyses will focus on virological, immunological, safety, antiretroviral treatment change and medication adherence. A comparison of costs and estimates of cost-effectiveness for the randomised comparison will be a critical component of this study. ART costs will be assessed across study arms. Health-care utilisation will be self-reported and then used to estimate costs. Safety data, viral loads and quality of life data will also be analysed.
The open label nature of the study allows routine care to be undertaken and the use of objective endpoints limit potential bias. The study has well defined and integrated clinical data collection and patient management systems that have been shown to be effective in a wide range of clinical settings.
The choice of N(t)RTIs in the SoC regimen is based on clinical judgement and may be guided by resistance testing if locally available. The NRTIs are not provided via the study. At the end of 96 weeks (completion of the protocol) study drug can be offered to all participants for a further 48 weeks as informed by the 48-week study results and clinical judgement. After 144 weeks study drug will no longer be available and composition of the participant's post-study regimen will be the clinician's decision.'
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 610 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase IIIB/IV Randomised Open-label Trial to Compare Dolutegravir + Pharmaco-enhanced Darunavir Versus Recommended Standard of Care Antiretroviral Regimens in Patients With HIV Infection Who Have Failed Recommended First Line Therapy. |
Actual Study Start Date : | November 1, 2017 |
Estimated Primary Completion Date : | September 30, 2019 |
Estimated Study Completion Date : | December 30, 2020 |

Arm | Intervention/treatment |
---|---|
Active Comparator: Standard of Care (SoC) arm
2 x NRTIs + darunavir/ritonavir 800mg/100mg po od
|
Drug: N(t)RTIs
Choice of N(t)RTI determined by clinician, guided by either genotypic resistance testing or use of a protocol-specified algorithm for N(t)RTI selection.
Other Name: Nucleoside/Nucleotide Reverse Transcription Inhibitors
Drug: Darunavir
800mg tablet by mouth once daily for 96 weeks.
Other Name: Prezista
Drug: Ritonavir
100mg tablet by mouth once daily for 96 weeks.
Other Name: Norvir
|
Experimental: Dolutegravir arm
Dolutegravir 50mg + darunavir/ritonavir 800mg/100mg po od
|
Drug: Dolutegravir
50mg tablet by mouth once daily for 96 weeks.
Other Name: Tivicay
Drug: Darunavir
800mg tablet by mouth once daily for 96 weeks.
Other Name: Prezista
Drug: Ritonavir
100mg tablet by mouth once daily for 96 weeks.
Other Name: Norvir
|
- The proportion of participants in each arm whose plasma viral load is <50 copies/mL at 48 weeks by intention to treat. [ Time Frame: At 48 weeks ]
- Proportion with plasma viral load <200 copies/mL [ Time Frame: At 48 and 96 weeks ]
- Proportion with plasma viral load <50 copies/mL where those stopping randomised therapy for any reason are classified as plasma viral load >50 copies/mL [ Time Frame: At 48 and 96 weeks ]
- Mean change in CD4+ cell count from baseline [ Time Frame: At 48 and 96 weeks ]
- Mean/median changes from baseline in fasted lipids (Total cholesterol, LDL-c, HDL-c, and triglycerides) [ Time Frame: At 48 and 96 weeks ]
- Total number of participants with any serious adverse events (SAEs), and the cumulative incidence of SAEs [ Time Frame: At 48 and 96 weeks ]
- Total number of opportunistic diseases (AIDS events), deaths and serious non-AIDS defining events and the cumulative incidence of these [ Time Frame: At 48 and 96 weeks ]
- Adverse events associated with cessation of randomly assigned therapy [ Time Frame: At 48 and 96 weeks ]
- Categorisation of neuropsychological adverse events [ Time Frame: At 48 and 96 weeks ]
- Proportion who stopped randomised therapy by reason for stopping [ Time Frame: At 48 and 96 weeks ]
- Patterns of genotypic HIV resistance associated with virological failure [ Time Frame: At 48 and 96 weeks ]
- Adherence assessment using participant 7-day recall self-report questionnaire [ Time Frame: At week 4 ]
- Quality of life and anxiety & depression assessed by participant questionnaire [ Time Frame: At 48 and 96 weeks ]
- Health care utilisation assessed by participant questionnaire [ Time Frame: At 48 and 96 weeks ]
- Cost of care assessment [ Time Frame: At 48 and 96 weeks ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- HIV-1 positive by licensed diagnostic test
- Aged ≥16 years of age (or minimum age as determined by local regulations or as legal requirements dictate)
- Failed first-line non-nucleoside reverse transcriptase inhibitor (NNRTI) + 2N(t)RTI combination therapy according to virological criteria, defined as at least two consecutive (≥7 days apart) pVL results >500 copies/mL after a minimum period of exposure to continuous NNRTI + 2N(t)RTI first-line therapy of 24 weeks (only the second pVL result needs to be within 45 days of randomisation)
- Able to provide written informed consent
Exclusion Criteria:
-
The following laboratory variables:
- absolute neutrophil count (ANC) <500 cells/µL
- haemoglobin <7.0 g/dL
- platelet count <50,000 cells/µL
- AST and/or ALT ≥5xULN OR ALT ≥3xULN and bilirubin ≥1.5xULN (with >35% direct bilirubin)
- Change in antiretroviral therapy within 12 weeks prior to randomisation
- Prior exposure to HIV protease inhibitors and/or HIV integrase inhibitors
- Patients with chronic viral hepatitis B infection defined by positive serum hepatitis B surface antigen
- Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy (INR >2.3), hypoalbuminemia (serum albumin <2.8g/dL), esophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- Anticipated need for Hepatitis C virus (HCV) therapy with interferon during the study
- Subject has creatinine clearance of <50 mL/min via CKD-EPI equation
- Current use of rifabutin or rifampicin
- Use of any contraindicated medications (as specified by product information sheets)
- Intercurrent illness requiring hospitalization
- An active opportunistic disease not under adequate control in the opinion of the investigator
- Pregnant or nursing mothers
- Patients with current alcohol or illicit substance use that in the opinion of the investigator might adversely affect participation in the study
- Patients deemed unlikely by the investigator to be able to remain in follow-up for the protocol-defined period

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03017872
Contact: Simone S Jacoby | +61 2 9385 0900 ext 50919 | sjacoby@kirby.unsw.edu.au |
Argentina | |
Hospital G de Agudos JM Ramos Mejia | Not yet recruiting |
Buenos Aires, Ciudad De Buenos Aires, Argentina, C1221ADC | |
Contact: Marcelo Losso 5411 4127 0276 mlosso@hivramos.org.ar | |
Contact: Guillermo Viloria 5411 4931 5252 gviloria@hivramos.org.ar | |
Principal Investigator: Marcelo Losso, M.D. | |
Hospital Nacional Prof Alejandro Posadas | Not yet recruiting |
El Palomar, Provincia De Buenos Aires, Argentina, 1684 | |
Contact: Lucia Esther Daciuk, M.D. 54 11 1544962605 luciadaciuk@yahoo.com.ar | |
Contact: Hector Laplume, M.D. 54 11 1560426461 hectorlaplume@gmail.com | |
Principal Investigator: Lucia Esther Daciuk, M.D. | |
Hospital Dr Diego Paroissien | Not yet recruiting |
Isidro Casanova, Provincia De Buenos Aires, Argentina, 1765 | |
Contact: Eduardo Warley 5411 1541 897 181 eduwarley@yahoo.com.ar | |
Contact: Maria Ines Vieni 5411 1136 877 377 ext 3340 inesvieni@gmail.com | |
Principal Investigator: Eduardo Warley, M.D. | |
CAICI | Not yet recruiting |
Rosario, Provincia De Santa Fe, Argentina, S2000PBJ | |
Contact: Sergio Lupo 54 9 341 515 7704 drsergiolupo@gmail.com | |
Contact: Luciana Peroni 54 341 424 8045 administracioncaici@gmail.com | |
Principal Investigator: Sergio Lupo, M.D. | |
Hospital Interzonal de Agudos San Juan de Dios | Not yet recruiting |
La Plata, Argentina, 1900 | |
Contact: Martha Michaan +54 9221 5765 131 mgmichaan@yahoo.com.ar | |
Principal Investigator: Martha Michaan, M.D. | |
Chile | |
Hospital San Borja-Arriaran | Not yet recruiting |
Santiago, Chile, 8360159 | |
Contact: Marcelo Wolff 562- 555 6206 marcewolff@yahoo.com | |
Contact: Gladys Allendes 562-555-6206 gladys_allendes@yahoo.es | |
Principal Investigator: Marcelo Wolff, MD | |
Colombia | |
ASISTENCIA Cientifica De Alta Complejidad S.A.S. | Not yet recruiting |
Bogota, Colombia, 110010 | |
Contact: Otto Sussmann 57-1- 5107600 ext 104 osussmann@gmail.com | |
Contact: Ana Julia Rojas 57-1-5107600 ext 128 coord.investigaciones@asistenciacientifica.com | |
Principal Investigator: Otto Sussmann, M.D. | |
India | |
YRG Care | Not yet recruiting |
Chennai, Tamil Nadu, India, 600113 | |
Contact: Nagalingeswaran Kumarasamy 91 917 691 2007 kumarasamy@yrgcare.org | |
Contact: Faith Beulah 91 44 39106811 beulah@yrgcare.org | |
Principal Investigator: Nagalingeswaran Kumarasamy, MD | |
Malaysia | |
University of Malaya Medical Centre | Not yet recruiting |
Kuala Lumpur, Malaysia, 59100 | |
Contact: Raja Iskandar Shah Raja Azwa 603-79493834 iskandar.azwa@gmail.com | |
Contact: Margaret Tan 603-79492622 margarettan455@gmail.com | |
Principal Investigator: Raja Iskandar Shah Raja Azwa, MBChB, MRCP | |
Mexico | |
Morales Vargas Centro de Investigacion SC | Not yet recruiting |
León, Guanajuato, Mexico, 37000 | |
Contact: Juan Luis Mosqueda Gomez +52 (477) 1310037 luis_mosqueda@yahoo.com | |
Contact: Jorge Morales Vargas +52 (477) 7160714 mnc.jorge@hotmail.com | |
Hospital Civil de Guadalajara | Not yet recruiting |
Guadalajara, Jalisco, Mexico, 44280 | |
Contact: Jaime Andrade-Villanueva jandradev@msn.com | |
Contact: Angeles González-Hernández 5233 3614 7586 angelesghdez1@gmail.com | |
Principal Investigator: Jaime Andrade-Villanueva, M.D. | |
Instituto Nacional de Ciencias Medicas y Nutriciòn Salvador Zubiran | Not yet recruiting |
Mexico City, Mexico, 14080 | |
Contact: Juan Sierra Madero 52 5556559675 jsmadero@yahoo.com | |
Contact: Izchel Loyo iz.inncm@outlook.com | |
Principal Investigator: Juan Sierra Madero, M.D. | |
South Africa | |
Desmond Tutu HIV Foundation | Recruiting |
Cape Town, South Africa, 7925 | |
Contact: Richard Kaplan Richard.Kaplan@hiv-research.org.za | |
Contact: Christie Heiberg 27 21 406 3621 Christie.Heiberg@hiv-research.org.za | |
Principal Investigator: Richard Kaplan, M.D. | |
Clinical HIV Research Unit (CHRU), Wits Health Consotium (Pty) Ltd | Recruiting |
Johannesburg, South Africa, 2041 | |
Contact: Noluthando Mwelase tmwelase@witshealth.co.za | |
Contact: Pauline Vunandala 27 11 276 8800 pvunandlala@witshealth.co.za | |
Principal Investigator: Noluthando Mwelase, MBCHB | |
Perinatal HIV Research Unit (PHRU), Chris Hani Baragwanath Hospital | Recruiting |
Soweto, South Africa, 1864 | |
Contact: Lerato Mohapi mohapil@hivsa.com | |
Contact: Debra Peters 27 11 989 9700 petersd@phru.co.za | |
Principal Investigator: Lerato Mohapi, BSc, MBBCh | |
Thailand | |
HIV-NAT (The HIV Netherlands Australia Thailand Research Collaboration), Thai Red Cross AIDS Research Centre | Recruiting |
Bangkok, Thailand, 10330 | |
Contact: Anchalee Avihingsanon +662 652 3040 ext 107 anchaleea2009@gmail.com | |
Contact: Kanitta Pussadee +662 652 3040 ext 202 kanitta.p@hivnat.org | |
Principal Investigator: Anchalee Avihingsanon, M.D. | |
Chiangrai Prachanukroh Hospital | Not yet recruiting |
Chiang Rai, Thailand, 57000 | |
Contact: Pacharee Kantipong 66818859195 pachareek@hotmail.com | |
Contact: Supawadee Pongprapass 66819616900 npudit@hotmail.com | |
Principal Investigator: Pacharee Kantipong, M.D. | |
Srinagarind Hospital, Khon Kaen University | Not yet recruiting |
Khon Kaen, Thailand, 40002 | |
Contact: Ploenchan Chetchotisakd 6643363168 ploencha@kku.ac.th | |
Contact: Anchalee Tiyabut 6643363169 atiyabut@yahoo.com | |
Principal Investigator: Ploenchan Chetchotisakd, M.D. | |
Bamrasnaradura Infectious Diseases Institute | Not yet recruiting |
Nonthaburi, Thailand, 11000 | |
Contact: Weerawat Manosuthi drweerawat@hotmail.com | |
Contact: Supeda Thongyen 6625903631 supeda_t@yahoo.com | |
Principal Investigator: Weerawat Manosuthi, M.D. | |
Zimbabwe | |
University of Zimbabwe Clinical Research Centre | Recruiting |
Harare, Zimbabwe, +263 | |
Contact: James G Hakim 263 772225489 Jhakim@mweb.co.zw | |
Contact: Shepherd Mudzingwa 263 4 701717 smudzingwa@yahoo.com | |
Principal Investigator: James G Hakim, M.D. |
Study Director: | David A Cooper | Kirby Institute |
Responsible Party: | Kirby Institute |
ClinicalTrials.gov Identifier: | NCT03017872 History of Changes |
Other Study ID Numbers: |
D2EFT |
First Posted: | January 11, 2017 Key Record Dates |
Last Update Posted: | January 12, 2018 |
Last Verified: | October 2017 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
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 |
Keywords provided by Kirby Institute:
HIV, second-line |
Additional relevant MeSH terms:
HIV Infections Acquired Immunodeficiency Syndrome Infection Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Slow Virus Diseases Ritonavir Darunavir |
Dolutegravir HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors HIV Integrase Inhibitors Integrase Inhibitors |