Clinical trial NCT04090151: The RESPOND Outcomes Study
Official title: The RESPOND Outcomes Study - A Study in the RESPOND Consortium (RESPOND: International Cohort Consortium of Infectious Diseases)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: HIV
Keywords: HIV
Prospective
Cohort
HCV
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
name: ViiV Healthcare
First posted: 2019-09-16
Enrollment: 37853
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participating clinics will enrol eligible persons living with HIV. Some clinics will enrol all their eligible persons living with HIV, and others will enrol a random sample.

Brief summary: The RESPOND Outcomes study is a research study around use of antiretroviral and other relevant drugs and long-term clinical outcomes in patients living with HIV. Data collected in this study will be used to answer key unanswered questions regarding treatment of people living with HIV.

Detailed description: The specific objectives, falling into three main categories, are as follows:

1. Monitor the uptake of newer antiretroviral treatment (ART) drugs and drugs for treatment of co-infections and co-morbidities;
2. To evaluate the safety profiles of the newer individual ART drugs when used in routine clinical practice as part of either first-line or subsequent treatment regimens.
3. Investigate long term outcomes and clinical disease progression overall and in specific sub-groups

The Outcomes study is a collaboration between investigators from clinics and cohorts across Europe, Australia and South America with a willingness to share data and to use a common follow-up schedule and assessment. Participating sites have a commitment to continue to follow this large cohort that is heterogeneous in both its demographic profile and in ART prescribing patterns thus resulting in enough power to answer many key clinical questions.

The Outcomes study is a study in the RESPOND International Cohort Consortium of Infectious Diseases. RESPOND is an innovative, flexible and dynamic cohort consortium for the study of infectious diseases, including HIV, built as a generic structure for facilitating multi stakeholder involvement. In RESPOND all collected data is part of a common data repository or 'data lake', which is stored in a database located at CHIP, Rigshospitalet, Copenhagen, Denmark. Data collection in RESPOND is modular with a core data collection module onto which additional modules/studies can be added. Pseudonymised patient data can be entered manually via an online secure platform or be electronically transferred from existing local, regional or national data structures to the data lake.

In the Outcomes study data will be collected at enrolment and at annual follow-up (FU) visits. For patients living with HIV-1 enrolled and under FU, demographic, laboratory, therapeutic and clinical data on HIV and viral hepatitis will be collected once a year. Clinical event data (except AIDS other than AIDS defining malignancies) will be collected in real-time on RESPOND event forms.

Eligibility criteria: Inclusion Criteria:

1. Signed Informed consent for the Outcomes study, if required by local/national legislation
2. Signed informed consent for the RESPOND consortium and data repository, if required by local/national legislation
3. Age ≥ 18 years of age
4. Confirmed HIV-1 infection
5. Persons receiving integrase inhibitor (INSTI) based antiretroviral therapy if have started after the later of 1/1/2012 and local cohort enrolment (i.e., during prospective follow-up in the cohort and after 1/1/2012) and have a CD4 and HIV viral load in the 12 months prior to starting INSTI or within 3 months after starting INSTI.
6. ART experienced and ART naïve persons not receiving INSTI if have a CD4 and HIV viral load in the 12 months prior to baseline or within 3 months after baseline (here, the latest of 1/1/2012 or cohort enrolment).
7. Persons lost to follow-up or who died before RESPOND enrolment should therefore still be included in the Outcomes study, provided they satisfy the other inclusion criteria.

Exclusion Criteria:

1. Persons receiving INSTI before 1/1/2012 are excluded from the Outcome study
2. Persons aged \< 18 at baseline are excluded from the Outcome study

Primary outcomes:
measure: Proportion of HIV positive persons who initiate treatment with newer antiretroviral drugs
timeFrame: From date of enrolment until the date of progression, lost to follow-up or death, whichever comes first, assessed up to 6 years
measure: Proportion of HIV positive persons who initiate treatment of co-infections
timeFrame: From date of enrolment until the date of progression, lost to follow-up or death, whichever comes first, assessed up to 6 years
measure: Proportion of HIV positive persons who initiate treatment of co-morbidities
timeFrame: From date of enrolment until the date of progression, lost to follow-up or death, whichever comes first, assessed up to 6 years
measure: Monitor changes in plasma CD4+ T-lymphocyte counts among persons exposed to newer individual ARVs
timeFrame: From date of enrolment until the date of progression, lost to follow-up or death, whichever comes first, assessed up to 6 years
measure: Monitor plasma HIV-RNA responses among persons exposed to newer individual ARVs
timeFrame: From date of enrolment until the date of progression, lost to follow-up or death, whichever comes first, assessed up to 6 years
measure: Evaluate the short- and long-term adverse effects of the newer ARVs when used in routine clinical practice
timeFrame: From date of enrolment until the date of progression, lost to follow-up or death, whichever comes first, assessed up to 6 years
measure: Investigate if adverse effects are increased in some patient sub-groups in order to build clinical risk prediction scores to aid effective strategies for risk reduction
timeFrame: From date of enrolment until the date of progression, lost to follow-up or death, whichever comes first, assessed up to 6 years
measure: Investigate if adverse effects are increased in some patient sub-groups in order to assess the risk and benefit for the individual
timeFrame: From date of enrolment until the date of progression, lost to follow-up or death, whichever comes first, assessed up to 6 years
measure: Investigate long term clinical outcomes and clinical disease progression overall and in specific sub-groups
timeFrame: From date of enrolment until the date of progression, lost to follow-up or death, whichever comes first, assessed up to 6 years
measure: Develop predictive risk-scores for the development of clinical outcomes to enable personalized decisions regarding risk and benefit of specific treatments in different demographic groups
timeFrame: From date of enrolment until the date of progression, lost to follow-up or death, whichever comes first, assessed up to 6 years
Secondary outcomes:
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: The Australian HIV Observational Database (AHOD)
state: New South Wales
city: Innsbruck
country: Austria
facility: Austrian HIV Cohort Study (AHIVCOS), Medizinische Universität Innsbruch
city: Brussels
country: Belgium
facility: CHU Saint-Pierre Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Copenhagen
country: Denmark
facility: The EuroSIDA Study, CHIP, Rigshospitalet
city: Nice
country: France
facility: Nice HIV Cohort, Centre Hospitalier Universitaire de Nice
city: Tbilisi
country: Georgia
facility: Georgian National AIDS Health Information System (AIDS HIS), IDACIRC
city: Bonn
country: Germany
facility: University Hospital Bonn
city: Cologne
country: Germany
facility: University Hospital Cologne
city: Frankfurt
country: Germany
facility: Frankfurt HIV Cohort Study, Goethe-University Frankfurt
city: Milano
country: Italy
facility: Italian Cohort Naive Antiretrovirals (ICONA)
city: Milan
country: Italy
facility: San Raffaele Scientific Institute, Ospedale San Raffaele
city: Modena
country: Italy
facility: Modena HIV Cohort, Università degli Studi di Modena
city: Amsterdam
country: Netherlands
facility: The ATHENA (AIDS Therapy Evaluation in the Netherlands) national observational HIV cohort, Stichting HIV Monitorin, AMC, University of Amsterdam
city: Badalona
country: Spain
facility: PISCIS Cohort Study, Germans Trias i Pujol University Hospital
city: Stockholm
country: Sweden
facility: Swedish InfCare HIV Cohort, Karolinska University Hospital
city: Zurich
country: Switzerland
facility: Swiss HIV Cohort Study (SHCS), University Hospital Zurich
city: London
country: United Kingdom
facility: Royal Free HIV Cohort Study, Royal Free Hospital
Study officials:
References:
citation: Obel N, Omland LH, Kronborg G, Larsen CS, Pedersen C, Pedersen G, Sorensen HT, Gerstoft J. Impact of non-HIV and HIV risk factors on survival in HIV-infected patients on HAART: a population-based nationwide cohort study. PLoS One. 2011;6(7):e22698. doi: 10.1371/journal.pone.0022698. Epub 2011 Jul 25.
citation: Smith CJ, Ryom L, Weber R, Morlat P, Pradier C, Reiss P, Kowalska JD, de Wit S, Law M, el Sadr W, Kirk O, Friis-Moller N, Monforte Ad, Phillips AN, Sabin CA, Lundgren JD; D:A:D Study Group. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet. 2014 Jul 19;384(9939):241-8. doi: 10.1016/S0140-6736(14)60604-8.
citation: Schouten J, Wit FW, Stolte IG, Kootstra NA, van der Valk M, Geerlings SE, Prins M, Reiss P; AGEhIV Cohort Study Group. Cross-sectional comparison of the prevalence of age-associated comorbidities and their risk factors between HIV-infected and uninfected individuals: the AGEhIV cohort study. Clin Infect Dis. 2014 Dec 15;59(12):1787-97. doi: 10.1093/cid/ciu701. Epub 2014 Sep 2.
citation: Chary A, Nguyen NN, Maiton K, Holodniy M. A review of drug-drug interactions in older HIV-infected patients. Expert Rev Clin Pharmacol. 2017 Dec;10(12):1329-1352. doi: 10.1080/17512433.2017.1377610. Epub 2017 Sep 19.
citation: Weber R, Sabin CA, Friis-Moller N, Reiss P, El-Sadr WM, Kirk O, Dabis F, Law MG, Pradier C, De Wit S, Akerlund B, Calvo G, Monforte Ad, Rickenbach M, Ledergerber B, Phillips AN, Lundgren JD. Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study. Arch Intern Med. 2006 Aug 14-28;166(15):1632-41. doi: 10.1001/archinte.166.15.1632.
citation: Kattakuzhy S, Gross C, Emmanuel B, Teferi G, Jenkins V, Silk R, Akoth E, Thomas A, Ahmed C, Espinosa M, Price A, Rosenthal E, Tang L, Wilson E, Bentzen S, Masur H, Kottilil S; ASCEND Providers. Expansion of Treatment for Hepatitis C Virus Infection by Task Shifting to Community-Based Nonspecialist Providers: A Nonrandomized Clinical Trial. Ann Intern Med. 2017 Sep 5;167(5):311-318. doi: 10.7326/M17-0118. Epub 2017 Aug 8.
citation: Falade-Nwulia O, Suarez-Cuervo C, Nelson DR, Fried MW, Segal JB, Sulkowski MS. Oral Direct-Acting Agent Therapy for Hepatitis C Virus Infection: A Systematic Review. Ann Intern Med. 2017 May 2;166(9):637-648. doi: 10.7326/M16-2575. Epub 2017 Mar 21.
citation: van der Meer AJ, Veldt BJ, Feld JJ, Wedemeyer H, Dufour JF, Lammert F, Duarte-Rojo A, Heathcote EJ, Manns MP, Kuske L, Zeuzem S, Hofmann WP, de Knegt RJ, Hansen BE, Janssen HL. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA. 2012 Dec 26;308(24):2584-93. doi: 10.1001/jama.2012.144878.
citation: Friis-Moller N, Ryom L, Smith C, Weber R, Reiss P, Dabis F, De Wit S, Monforte AD, Kirk O, Fontas E, Sabin C, Phillips A, Lundgren J, Law M; D:A:D study group. An updated prediction model of the global risk of cardiovascular disease in HIV-positive persons: The Data-collection on Adverse Effects of Anti-HIV Drugs (D:A:D) study. Eur J Prev Cardiol. 2016 Jan;23(2):214-23. doi: 10.1177/2047487315579291. Epub 2015 Apr 16.
citation: Mocroft A, Lundgren JD, Ross M, Fux CA, Reiss P, Moranne O, Morlat P, Monforte Ad, Kirk O, Ryom L; Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) Study. Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate: a prospective international cohort study. Lancet HIV. 2016 Jan;3(1):e23-32. doi: 10.1016/S2352-3018(15)00211-8. Epub 2015 Nov 17.
citation: Bruyand M, Ryom L, Shepherd L, Fatkenheuer G, Grulich A, Reiss P, de Wit S, D Arminio Monforte A, Furrer H, Pradier C, Lundgren J, Sabin C; D:A:D study group. Cancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy: the D: A: D study. J Acquir Immune Defic Syndr. 2015 Apr 15;68(5):568-77. doi: 10.1097/QAI.0000000000000523.
citation: Neesgaard B, Greenberg L, Miro JM, Grabmeier-Pfistershammer K, Wandeler G, Smith C, De Wit S, Wit F, Pelchen-Matthews A, Mussini C, Castagna A, Pradier C, d'Arminio Monforte A, Vehreschild JJ, Sonnerborg A, Anne AV, Carr A, Bansi-Matharu L, Lundgren JD, Garges H, Rogatto F, Zangerle R, Gunthard HF, Rasmussen LD, Necsoi C, van der Valk M, Menozzi M, Muccini C, Peters L, Mocroft A, Ryom L. Associations between integrase strand-transfer inhibitors and cardiovascular disease in people living with HIV: a multicentre prospective study from the RESPOND cohort consortium. Lancet HIV. 2022 Jul;9(7):e474-e485. doi: 10.1016/S2352-3018(22)00094-7. Epub 2022 Jun 7.