HIV/AIDSIMPACNEONCT04735445
IMPACt of an Enhanced Screening Program on the Detection of Non-AIDS NEOplasms in HIV Patients
A study testing Digital rectal exam and / or anal cytology (day 1 and after 36 months), Semestral digital rectal exam and / or anal cytology if abnormal → ANOSCOPY with biopsy and Cervical cytology and cervical sample for HPV detection (day 1 and after 36 months) in people with HIV/AIDS and Cancer, run by Felix Gutierrez at 1 site in Spain.
Trial summary
Introduction: The incidence of malignancies is higher in the HIV-infected population than in the general population, and it is already one of the leading causes of death in people living with the virus. It is estimated that the situation will be aggravated by the progressive aging of the HIV-infected population. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- Digital rectal exam and / or anal cytology (day 1 and after 36 months), Semestral digital rectal exam and / or anal cytology if abnormal → ANOSCOPY with biopsy and Cervical cytology and cervical sample for HPV detection (day 1 and after 36 months)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4,638 participants
- Where
- 1 siteSpain
- Study dates
- 11 Nov 2019to 30 Jun 2023
- Phase
- Interventional
- 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
- Male ≥40 years or woman ≥18 years
- Informed Consent signed
Who cannot join
- Active AIDS defining disease
- Antecedent of cancer
- Terminal disease
- Pregnancy or breastfeeding
- Patient rejection
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
Elche, Alicante, 03203
About this study
Official title: IMPACt of an Enhanced Screening Program on the Detection of Non-AIDS NEOplasms in Patients With Human Immunodeficiency Virus (HIV) Infection
Introduction: The incidence of malignancies is higher in the HIV-infected population than in the general population, and it is already one of the leading causes of death in people living with the virus. It is estimated that the situation will be aggravated by the progressive aging of the HIV-infected population. Early diagnosis through enhanced cancer screening can be critical in reducing mortality, but may increase expenditure and harms associated with adverse events. This strategy should then be considered only when the benefits clearly outweigh the harms. There are currently no studies on expanded cancer screening in patients with HIV, and available information from the point of view of costeffectiveness or cost-utility is scarce.
Hypothesis: An enhanced program for non-aids cancer screening in patients with HIV can lead to early diagnosis and improve the prognosis of these patients, with an acceptable rate of unnecessary interventions and being cost-effective.
Read more
Objectives: To evaluate the efficacy, safety and efficiency of an enhanced screening program for the early diagnosis of cancer in HIV patients compared to standard practice within the cohort of the National AIDS Research Network (CoRIS).
Specific objectives: 1) To compare the incidence of early diagnosed cancer with enhanced screening versus conventional screening; 2) To assess the incidence of early diagnosed cancer and its overall incidence in the CoRIS cohort; 3) To analyze safety of the program: adverse events and unnecessary interventions; 4) To compare the obtained data stratifying by gender and 5) To analyze the cost-utility of the program.
Expected results: 1) To generate scientific evidence to inform decision makers on the advisability of implementing an enhanced screening program of cancer in HIV-infected patients; 2) To broaden knowledge about the programs of early detection of cancer in vulnerable populations and their economic evaluation from the perspective of the National Health Service.
Read the detailed description
Non-AIDS-Defining Cancers (NADCs) are an important cause of morbidity and mortality in the population living with the human immunodeficiency virus (PLHIV), being currently one of the most frequent causes of death. Due to several reasons, the incidence of this type of tumors in PLHIV has increased 2-3 times with respect to the general population (GP). In a recent systematic review, with more than 600,000 PLHIV and 10,891 new cases of cancer, it is demonstrated how the incidence of NADCs has progressively increased since the introduction of combined antiretroviral therapy (ART), probably reflecting better viral-immune control and aging associated with the increase in overall survival of patients living with the virus. The most frequent cancers are lung cancer, hepatocellular carcinoma, anal carcinoma and cervical carcinoma, although some studies have suggested that there could also be a higher incidence and / or severity of other malignant tumors, such as breast cancer, prostate, colorectal or skin, including melanomas. In the era of ART, lung cancer has become the most frequent and deadliest cause of non-AIDS-associated cancer in PLHIV, and greater lethality has been documented in PLHIV than in GP.
The causes of this increased incidence of NADCs are not well known and there are several factors that could influence, including the oncogenic effects of the virus, immunosuppression, chronic inflammation and immune activation, ART exposure, higher rates of coinfection with other oncogenic viruses and traditional cancer risk factors such as smoking. It is estimated that at least 1 in 3 PLHIV will die due to malignant neoplasms in the coming years. There is currently no consensus on the best screening strategies in this population, strategies that seem increasingly necessary considering the progressive aging of the infected population and the increase in the incidence of these neoplasms.
In some of the clinical practice guidelines in PLHIV, such as the Spanish Gesida or other European ones, the screening strategies for neoplasms recommended in GP have been incorporated, in which they have shown benefit in terms of mortality or greater probabilities of therapeutic success. However, these benefits have not been confirmed in PLHIV, in which this type of strategy could be insufficient.
Moreover, there are currently no established recommendations for GP screening on two of the main neoplasms of PLHIV, such as lung and anal. For this reason, it is necessary to generate scientific evidence that determines which is the most convenient strategy to reduce the morbidity and mortality associated with NADCs in PLHIV. Then, the evaluation of an enhanced program of screening by conducting a clinical trial, in which patients are randomized to one of the two strategies (enhanced screening versus standard of care practice), is the ideal design to generate scientific evidence. This knowledge could be useful to determine if the benefits of the enhanced screening outweighs the harms and if it is cost-effective for the National Health Service.
Objectives:
General objectives: To evaluate the efficacy, safety and efficiency of an expanded screening program for the early diagnosis of cancer in patients with HIV compared to usual practice, within the framework of the Spanish AIDS Research Network (RIS).
Specific objectives: 1) To compare the incidence of early diagnosed cancer with extended screening versus usual practice; 2) To estimate the incidence of early diagnosed cancer and its overall incidence in the CoRIS cohort; 3) To analyze safety of the program: adverse events and unnecessary interventions; 4) To compare the incidence data described above stratifying by gender and 5) To analyze the cost-utility of the extended screening.
Early detection of cancer would entail clinical benefits, both in terms of survival and quality of life, for the population with HIV. The evaluation of the cost-utility of the program is also a main objective, since the benefits of therapy for cancer in the earliest stages should compensate for the use of the additional resources of the National Health System.
Methodology: Research project that includes randomization by patient, stratified according to sex, to one of the following groups:
- Enhanced intervention group: expanded screening for early detection of lung, liver, anal, cervical, breast, prostate, colorectal and skin cancer.
- Conventional intervention group: standard screening in the participating centers, adjusted to the recommendations of the European AIDS Society (EACS).
Work plan and timeline
This project is based on a collaborative methodology in which all groups work in a coordinated manner, under the direction of the Principal Investigator, Dr. Félix Gutiérrez. The tasks that make up this project are broken down below:
- Recruitment of patients and randomization according to the sex of each patient to a conventional intervention or an extended intervention. This phase is already started in some of the centers that make up the consortium, but it must continue to reach the desired sample size. Depending on whether the patients are assigned to the conventional screening group or the extended screening group, their inclusion in the following tasks will be different.
- Completion of the questionnaires (annual) on sociodemographic and toxic data in each of the participating centers.
- Blood samples withdrawal and storage of plasma for ulterior determination of biomarkers annually.
- The digital examination and anal (semi-annual) cytology, cervical cytology (semi-annual) will be performed in the HIV Units of the participating centers.
- The General Inspection in search of skin lesions suggestive of malignancy on an annual basis will be carried out in the HIV Units of the participating centers that will be previously trained for it. In case of suspicion, it will be referred to the specialist of each center.
- The semi-annual monitoring of the clinical trial will be carried out by the CRO contracted for that purpose.
- At 30 months, the telematic session for closing the trial will be held.
- Statistical analysis of the data. The analysis of the data will be carried out transversely after the first year, after the second and after the third year, where the final conclusions of the study can be established.
- Dissemination of the results during the last 3 months: communications to congresses and writing of articles. Proposal for inclusion in Clinical Guidelines.
- Being tested
- Digital rectal exam and / or anal cytology (day 1 and after 36 months), Semestral digital rectal exam and / or anal cytology if abnormal → ANOSCOPY with biopsy, Cervical cytology and cervical sample for HPV detection (day 1 and after 36 months), Semestral cervical cytology and cervical sample for HPV detection, Appointment for mammography (day 1 and after 36 months)
- Keywords
- HIV, Neoplasm, Screening, Early diagnosis
- Medical subject headings
- Acquired Immunodeficiency Syndrome, Neoplasms, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Digital rectal exam and / or anal cytology (day 1 and after 36 months)Diagnostic test
For anal screening in MSM man or woman with abnormal cervical cytology, genital warts or having anal sex (day 1 and after 36 months)
Semestral digital rectal exam and / or anal cytology if abnormal → ANOSCOPY with biopsyDiagnostic test
For anal screening in MSM man or woman with abnormal cervical cytology, genital warts or having anal sex (semestral)
Cervical cytology and cervical sample for HPV detection (day 1 and after 36 months)Diagnostic test
For Cervix Screening in sexually active woman (day 1 and after 36 months)
Semestral cervical cytology and cervical sample for HPV detectionDiagnostic test
For Cervix Screening in sexually active woman (semestral)
Appointment for mammography (day 1 and after 36 months)Diagnostic test
For Breast Screening in woman between 50-70 years old (day 1 and after 36 months)
Annual appointment for mammographyDiagnostic test
For Breast Screening in woman between 45-70 years old (annual)
Semestral appointment for liver ultrasoundDiagnostic test
For Hepatic Screening:
Cirrhosis or Chronic HBV, and meet any of the following risk factors:
- Asian male> 40 years old
- Asian woman> 50 years old
- African man or woman
- HCC family history
Semestral appointment for liver ultrasoundDiagnostic test
Having chronic liver disease with fibrosis ≥ F3 or Presents chronic HBV
Semestral blood collection for alpha-fetoprotein and others hepatic biomarkers determinationDiagnostic test
Having chronic liver disease with fibrosis ≥ F3 or Presents chronic HBV
Fecal occult blood test (day 1 and after 36 months)Diagnostic test
For Colon Screening:
Age between 50-70 years old
Annual fecal occult blood testDiagnostic test
For Colon Screening:
Age older than 40 years
Digital rectal exam and PSA determination (day 1 and after 36 months)Diagnostic test
For Prostate Screening:
Man older than 50 years
Annual digital rectal exam and PSA determinationDiagnostic test
For Prostate Screening:
Man older than 50 years
Annual appointment for low dose computed tomography for lung screeningDiagnostic test
For Lung Screening: should accomplish
ALL the following criteria:
- Age > 40 years
- Active smoker or former smoker<3 years, with IPY ≥20. IPY: index of packages-year: nº packages that smoke per day x nº years smoking
- No contraindications for thoracic surgery
- No lung infection in the last 2 months
Annual general inspection for skin lesions suggestive of malignancyDiagnostic test
For Skin Screening:
Woman ≥18 years Man ≥40 years
| Study group | Role | What they receive |
|---|---|---|
| Conventional screening | Active comparator | Standard screening in the participating centers, adjusted to the recommendations of the European AIDS Society (EACS). Receives: Diagnostic Test: Digital rectal exam and / or anal cytology (day 1 and after 36 months); Diagnostic Test: Cervical cytology and cervical sample for HPV detection (day 1 and after 36 months); Diagnostic Test: Appointment for mammography (day 1 and after 36 months); Diagnostic Test: Semestral appointment for liver ultrasound; Diagnostic Test: Fecal occult blood test (day 1 and after 36 months); Diagnostic Test: Digital rectal exam and PSA determination (day 1 and after 36 months) |
| Enhanced screening | Experimental | Expanded screening for early detection of lung, liver, anal, cervical, breast, prostate, colorectal and skin cancer. Receives: Diagnostic Test: Semestral digital rectal exam and / or anal cytology if abnormal → ANOSCOPY with biopsy; Diagnostic Test: Semestral cervical cytology and cervical sample for HPV detection; Diagnostic Test: Annual appointment for mammography; Diagnostic Test: Semestral appointment for liver ultrasound; Diagnostic Test: Semestral blood collection for alpha-fetoprotein and others hepatic biomarkers determination; Diagnostic Test: Annual fecal occult blood test; Diagnostic Test: Annual digital rectal exam and PSA determination; Diagnostic Test: Annual appointment for low dose computed tomography for lung screening; Diagnostic Test: Annual general inspection for skin lesions suggestive of malignancy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Non-AIDS defining cancers incidence
The incidence of different neoplasms not considered as AIDS defining cancers compared between two arms
Measured: through study completion, an average of 1 year
Survival rate
Comparison in survival terms between conventional and enhanced screening arms
Measured: through study completion, an average of 1 year
Secondary outcomes (2)
Safety of the screening: adverse events
Analyze the safety of the screening program, analyzing its adverse events, including those unnecessary interventions
Measured: through study completion, an average of 1 year
Cost-efectiveness
Analyze the cost-utility ratio of the extended screening program.
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2021
- Study start11 Nov 2019
- Primary completion31 Dec 2022 (estimated)
- Study completion30 Jun 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for HIV/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 N/A
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 4,638 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Felix Gutierrez
- Sponsor type
- University, hospital or other
- Collaborators
- Instituto de Salud Carlos III, Hospital General Universitario Reina Sofía de Murcia, Hospital Universitario Reina Sofia de Cordoba, Hospital General Universitario de Alicante, Hospital Clinic of Barcelona, Hospital Universitario Ramon y Cajal, Hospital General Universitario Santa Lucia, Fundación de Investigación Biomédica - Hospital Universitario de La Princesa, University of Guadalajara, Hospital Universitario Virgen de la Arrixaca, Parc Taulí Hospital Universitari, Hospital Universitario La Fe, Germans Trias i Pujol Hospital, Complejo Hospitalario Universitario de Albacete, Hospital Universitario Fundación Alcorcón, Hospital General Universitario Elche
- Responsible party
- Sponsor-investigator, Felix Gutierrez, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
- Investigators
- Félix Gutiérrez-Rodero, PhD, Principal investigator, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04735445
- Sponsor's protocol ID
- IMPACNEO
- Acronym
- IMPACNEO
- Status last verified
- Feb 2021
- First submitted
- 27 Jan 2021
- Last updated
- 3 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Lopez C, Masia M, Padilla S, Aquilino A, Bas C, Gutierrez F. [Deaths due to non-AIDS diseases among HIV infected patients: A 14-year study (1998-2011)]. Enferm Infecc Microbiol Clin. 2016 Apr;34(4):222-7. doi: 10.1016/j.eimc.2015.04.010. Epub 2015 Jun 18. Spanish.
PubMed 26093959Garcia-Abellan J, Del Rio L, Garcia JA, Padilla S, Vivancos MJ, Del Romero J, Asensi V, Hernando A, Garcia-Fraile L, Masia M, Gutierrez F; la Cohorte de la Red Nacional de Sida (CoRIS). Risk of cancer in HIV-infected patients in Spain, 2004-2015. The CoRIS cohort study. Enferm Infecc Microbiol Clin (Engl Ed). 2019 Oct;37(8):502-508. doi: 10.1016/j.eimc.2018.11.011. Epub 2019 Jan 22. English, Spanish.
PubMed 30679001Smith 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.
PubMed 25042234Shiels MS, Cole SR, Kirk GD, Poole C. A meta-analysis of the incidence of non-AIDS cancers in HIV-infected individuals. J Acquir Immune Defic Syndr. 2009 Dec;52(5):611-22. doi: 10.1097/QAI.0b013e3181b327ca.
PubMed 19770804Grulich AE, van Leeuwen MT, Falster MO, Vajdic CM. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet. 2007 Jul 7;370(9581):59-67. doi: 10.1016/S0140-6736(07)61050-2.
PubMed 17617273Althoff KN, McGinnis KA, Wyatt CM, Freiberg MS, Gilbert C, Oursler KK, Rimland D, Rodriguez-Barradas MC, Dubrow R, Park LS, Skanderson M, Shiels MS, Gange SJ, Gebo KA, Justice AC; Veterans Aging Cohort Study (VACS). Comparison of risk and age at diagnosis of myocardial infarction, end-stage renal disease, and non-AIDS-defining cancer in HIV-infected versus uninfected adults. Clin Infect Dis. 2015 Feb 15;60(4):627-38. doi: 10.1093/cid/ciu869. Epub 2014 Oct 30.
PubMed 25362204Cobucci RN, Lima PH, de Souza PC, Costa VV, Cornetta Mda C, Fernandes JV, Goncalves AK. Assessing the impact of HAART on the incidence of defining and non-defining AIDS cancers among patients with HIV/AIDS: a systematic review. J Infect Public Health. 2015 Jan-Feb;8(1):1-10. doi: 10.1016/j.jiph.2014.08.003. Epub 2014 Oct 5.
PubMed 25294086Masia M, Padilla S, Alvarez D, Lopez JC, Santos I, Soriano V, Hernandez-Quero J, Santos J, Tural C, del Amo J, Gutierrez F; CoRIS. Risk, predictors, and mortality associated with non-AIDS events in newly diagnosed HIV-infected patients: role of antiretroviral therapy. AIDS. 2013 Jan 14;27(2):181-9. doi: 10.1097/QAD.0b013e32835a1156.
PubMed 23018442Patel P, Hanson DL, Sullivan PS, Novak RM, Moorman AC, Tong TC, Holmberg SD, Brooks JT; Adult and Adolescent Spectrum of Disease Project and HIV Outpatient Study Investigators. Incidence of types of cancer among HIV-infected persons compared with the general population in the United States, 1992-2003. Ann Intern Med. 2008 May 20;148(10):728-36. doi: 10.7326/0003-4819-148-10-200805200-00005.
PubMed 18490686Shiels MS, Engels EA. Evolving epidemiology of HIV-associated malignancies. Curr Opin HIV AIDS. 2017 Jan;12(1):6-11. doi: 10.1097/COH.0000000000000327.
PubMed 27749369Croxford S, Kitching A, Desai S, Kall M, Edelstein M, Skingsley A, Burns F, Copas A, Brown AE, Sullivan AK, Delpech V. Mortality and causes of death in people diagnosed with HIV in the era of highly active antiretroviral therapy compared with the general population: an analysis of a national observational cohort. Lancet Public Health. 2017 Jan;2(1):e35-e46. doi: 10.1016/S2468-2667(16)30020-2. Epub 2016 Dec 15.
PubMed 29249478Wang YH, Shen XD. Human immunodeficiency virus infection and mortality risk among lung cancer patients: A systematic review and meta-analysis. Medicine (Baltimore). 2018 Apr;97(15):e0361. doi: 10.1097/MD.0000000000010361.
PubMed 29642182Trickey A, May MT, Gill MJ, Grabar S, Vehreschild J, Wit FWNM, Bonnet F, Cavassini M, Abgrall S, Berenguer J, Wyen C, Reiss P, Grabmeier-Pfistershammer K, Guest JL, Shepherd L, Teira R, d'Arminio Monforte A, Del Amo J, Justice A, Costagliola D, Sterne JAC. Cause-specific mortality after diagnosis of cancer among HIV-positive patients: A collaborative analysis of cohort studies. Int J Cancer. 2020 Jun 1;146(11):3134-3146. doi: 10.1002/ijc.32895. Epub 2020 Mar 12.
PubMed 32003460Santos J, Valencia E; Panel de Expertos de GeSIDA. [Consensus statement on the clinical management of non-AIDS defining malignancies. GeSIDA expert panel]. Enferm Infecc Microbiol Clin. 2014 Oct;32(8):515-22. doi: 10.1016/j.eimc.2014.04.008. Epub 2014 Jun 20. Spanish.
PubMed 24953385GBD 2015 HIV Collaborators. Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015: the Global Burden of Disease Study 2015. Lancet HIV. 2016 Aug;3(8):e361-e387. doi: 10.1016/S2352-3018(16)30087-X. Epub 2016 Jul 19.
PubMed 27470028
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- IMPACt of an Enhanced Screening Program on the Detection of Non-AIDS NEOplasms in Patients With Human Immunodeficiency Virus (HIV) Infection
- ClinicalTrials.gov ID
- NCT04735445
- Acronym / sponsor ID
- IMPACNEO / IMPACNEO
- Keywords
- HIV, Neoplasm, Screening, Early diagnosis
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 4,638 participants (estimated)
- Lead sponsor
- Felix GutierrezUniversity, hospital or other
- Collaborators
- Instituto de Salud Carlos III, Hospital General Universitario Reina Sofía de Murcia, Hospital Universitario Reina Sofia de Cordoba, Hospital General Universitario de Alicante, Hospital Clinic of Barcelona, Hospital Universitario Ramon y Cajal, Hospital General Universitario Santa Lucia, Fundación de Investigación Biomédica - Hospital Universitario de La Princesa, University of Guadalajara, Hospital Universitario Virgen de la Arrixaca, Parc Taulí Hospital Universitari, Hospital Universitario La Fe, Germans Trias i Pujol Hospital, Complejo Hospitalario Universitario de Albacete, Hospital Universitario Fundación Alcorcón, Hospital General Universitario Elche
- Study start
- 11 Nov 2019 (actual)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 30 Jun 2023 (estimated)
- First posted
- 3 Feb 2021 (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.
Introduction: The incidence of malignancies is higher in the HIV-infected population than in the general population, and it is already one of the leading causes of death in people living with the virus. It is estimated that the situation will be aggravated by the progressive aging of the HIV-infected population. Early diagnosis through enhanced cancer screening can be critical in reducing mortality, but may increase expenditure and harms associated with adverse events. This strategy should then be considered only when the benefits clearly outweigh the harms. There are currently no studies on expanded cancer screening in patients with HIV, and available information from the point of view of costeffectiveness or cost-utility is scarce.
Hypothesis: An enhanced program for non-aids cancer screening in patients with HIV can lead to early diagnosis and improve the prognosis of these patients, with an acceptable rate of unnecessary interventions and being cost-effective.
Objectives: To evaluate the efficacy, safety and efficiency of an enhanced screening program for the early diagnosis of cancer in HIV patients compared to standard practice within the cohort of the National AIDS Research Network (CoRIS).
Specific objectives: 1) To compare the incidence of early diagnosed cancer with enhanced screening versus conventional screening; 2) To assess the incidence of early diagnosed cancer and its overall incidence in the CoRIS cohort; 3) To analyze safety of the program: adverse events and unnecessary interventions; 4) To compare the obtained data stratifying by gender and 5) To analyze the cost-utility of the program.
Expected results: 1) To generate scientific evidence to inform decision makers on the advisability of implementing an enhanced screening program of cancer in HIV-infected patients; 2) To broaden knowledge about the programs of early detection of cancer in vulnerable populations and their economic evaluation from the perspective of the National Health Service.
Detailed description
Non-AIDS-Defining Cancers (NADCs) are an important cause of morbidity and mortality in the population living with the human immunodeficiency virus (PLHIV), being currently one of the most frequent causes of death. Due to several reasons, the incidence of this type of tumors in PLHIV has increased 2-3 times with respect to the general population (GP). In a recent systematic review, with more than 600,000 PLHIV and 10,891 new cases of cancer, it is demonstrated how the incidence of NADCs has progressively increased since the introduction of combined antiretroviral therapy (ART), probably reflecting better viral-immune control and aging associated with the increase in overall survival of patients living with the virus. The most frequent cancers are lung cancer, hepatocellular carcinoma, anal carcinoma and cervical carcinoma, although some studies have suggested that there could also be a higher incidence and / or severity of other malignant tumors, such as breast cancer, prostate, colorectal or skin, including melanomas. In the era of ART, lung cancer has become the most frequent and deadliest cause of non-AIDS-associated cancer in PLHIV, and greater lethality has been documented in PLHIV than in GP.
The causes of this increased incidence of NADCs are not well known and there are several factors that could influence, including the oncogenic effects of the virus, immunosuppression, chronic inflammation and immune activation, ART exposure, higher rates of coinfection with other oncogenic viruses and traditional cancer risk factors such as smoking. It is estimated that at least 1 in 3 PLHIV will die due to malignant neoplasms in the coming years. There is currently no consensus on the best screening strategies in this population, strategies that seem increasingly necessary considering the progressive aging of the infected population and the increase in the incidence of these neoplasms.
In some of the clinical practice guidelines in PLHIV, such as the Spanish Gesida or other European ones, the screening strategies for neoplasms recommended in GP have been incorporated, in which they have shown benefit in terms of mortality or greater probabilities of therapeutic success. However, these benefits have not been confirmed in PLHIV, in which this type of strategy could be insufficient.
Moreover, there are currently no established recommendations for GP screening on two of the main neoplasms of PLHIV, such as lung and anal. For this reason, it is necessary to generate scientific evidence that determines which is the most convenient strategy to reduce the morbidity and mortality associated with NADCs in PLHIV. Then, the evaluation of an enhanced program of screening by conducting a clinical trial, in which patients are randomized to one of the two strategies (enhanced screening versus standard of care practice), is the ideal design to generate scientific evidence. This knowledge could be useful to determine if the benefits of the enhanced screening outweighs the harms and if it is cost-effective for the National Health Service.
Objectives:
General objectives: To evaluate the efficacy, safety and efficiency of an expanded screening program for the early diagnosis of cancer in patients with HIV compared to usual practice, within the framework of the Spanish AIDS Research Network (RIS).
Specific objectives: 1) To compare the incidence of early diagnosed cancer with extended screening versus usual practice; 2) To estimate the incidence of early diagnosed cancer and its overall incidence in the CoRIS cohort; 3) To analyze safety of the program: adverse events and unnecessary interventions; 4) To compare the incidence data described above stratifying by gender and 5) To analyze the cost-utility of the extended screening.
Early detection of cancer would entail clinical benefits, both in terms of survival and quality of life, for the population with HIV. The evaluation of the cost-utility of the program is also a main objective, since the benefits of therapy for cancer in the earliest stages should compensate for the use of the additional resources of the National Health System.
Methodology: Research project that includes randomization by patient, stratified according to sex, to one of the following groups:
- Enhanced intervention group: expanded screening for early detection of lung, liver, anal, cervical, breast, prostate, colorectal and skin cancer.
- Conventional intervention group: standard screening in the participating centers, adjusted to the recommendations of the European AIDS Society (EACS).
Work plan and timeline
This project is based on a collaborative methodology in which all groups work in a coordinated manner, under the direction of the Principal Investigator, Dr. Félix Gutiérrez. The tasks that make up this project are broken down below:
- Recruitment of patients and randomization according to the sex of each patient to a conventional intervention or an extended intervention. This phase is already started in some of the centers that make up the consortium, but it must continue to reach the desired sample size. Depending on whether the patients are assigned to the conventional screening group or the extended screening group, their inclusion in the following tasks will be different.
- Completion of the questionnaires (annual) on sociodemographic and toxic data in each of the participating centers.
- Blood samples withdrawal and storage of plasma for ulterior determination of biomarkers annually.
- The digital examination and anal (semi-annual) cytology, cervical cytology (semi-annual) will be performed in the HIV Units of the participating centers.
- The General Inspection in search of skin lesions suggestive of malignancy on an annual basis will be carried out in the HIV Units of the participating centers that will be previously trained for it. In case of suspicion, it will be referred to the specialist of each center.
- The semi-annual monitoring of the clinical trial will be carried out by the CRO contracted for that purpose.
- At 30 months, the telematic session for closing the trial will be held.
- Statistical analysis of the data. The analysis of the data will be carried out transversely after the first year, after the second and after the third year, where the final conclusions of the study can be established.
- Dissemination of the results during the last 3 months: communications to congresses and writing of articles. Proposal for inclusion in Clinical Guidelines.
Study design
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Conventional screening | Active comparator | Diagnostic Test: Digital rectal exam and / or anal cytology (day 1 and after 36 months), Diagnostic Test: Cervical cytology and cervical sample for HPV detection (day 1 and after 36 months), Diagnostic Test: Appointment for mammography (day 1 and after 36 months), Diagnostic Test: Semestral appointment for liver ultrasound, Diagnostic Test: Fecal occult blood test (day 1 and after 36 months), Diagnostic Test: Digital rectal exam and PSA determination (day 1 and after 36 months)Standard screening in the participating centers, adjusted to the recommendations of the European AIDS Society (EACS). |
| Enhanced screening | Experimental | Diagnostic Test: Semestral digital rectal exam and / or anal cytology if abnormal → ANOSCOPY with biopsy, Diagnostic Test: Semestral cervical cytology and cervical sample for HPV detection, Diagnostic Test: Annual appointment for mammography, Diagnostic Test: Semestral appointment for liver ultrasound, Diagnostic Test: Semestral blood collection for alpha-fetoprotein and others hepatic biomarkers determination, Diagnostic Test: Annual fecal occult blood test, Diagnostic Test: Annual digital rectal exam and PSA determination, Diagnostic Test: Annual appointment for low dose computed tomography for lung screening, Diagnostic Test: Annual general inspection for skin lesions suggestive of malignancyExpanded screening for early detection of lung, liver, anal, cervical, breast, prostate, colorectal and skin cancer. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Male ≥40 years or woman ≥18 years
- Informed Consent signed
Key exclusion criteria (5 listed)
- Active AIDS defining disease
- Antecedent of cancer
- Terminal disease
- Pregnancy or breastfeeding
- Patient rejection
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 |
|---|---|---|
| Digital rectal exam and / or anal cytology (day 1 and after 36 months)For anal screening in MSM man or woman with abnormal cervical cytology, genital warts or having anal sex (day 1 and after 36 months) | Diagnostic test | Conventional screening |
| Semestral digital rectal exam and / or anal cytology if abnormal → ANOSCOPY with biopsyFor anal screening in MSM man or woman with abnormal cervical cytology, genital warts or having anal sex (semestral) | Diagnostic test | Enhanced screening |
| Cervical cytology and cervical sample for HPV detection (day 1 and after 36 months)For Cervix Screening in sexually active woman (day 1 and after 36 months) | Diagnostic test | Conventional screening |
| Semestral cervical cytology and cervical sample for HPV detectionFor Cervix Screening in sexually active woman (semestral) | Diagnostic test | Enhanced screening |
| Appointment for mammography (day 1 and after 36 months)For Breast Screening in woman between 50-70 years old (day 1 and after 36 months) | Diagnostic test | Conventional screening |
| Annual appointment for mammographyFor Breast Screening in woman between 45-70 years old (annual) | Diagnostic test | Enhanced screening |
| Semestral appointment for liver ultrasoundFor Hepatic Screening: Cirrhosis or Chronic HBV, and meet any of the following risk factors: * Asian male> 40 years old * Asian woman> 50 years old * African man or woman * HCC family history | Diagnostic test | Conventional screening |
| Semestral appointment for liver ultrasoundHaving chronic liver disease with fibrosis ≥ F3 or Presents chronic HBV | Diagnostic test | Enhanced screening |
| Semestral blood collection for alpha-fetoprotein and others hepatic biomarkers determinationHaving chronic liver disease with fibrosis ≥ F3 or Presents chronic HBV | Diagnostic test | Enhanced screening |
| Fecal occult blood test (day 1 and after 36 months)For Colon Screening: Age between 50-70 years old | Diagnostic test | Conventional screening |
| Annual fecal occult blood testFor Colon Screening: Age older than 40 years | Diagnostic test | Enhanced screening |
| Digital rectal exam and PSA determination (day 1 and after 36 months)For Prostate Screening: Man older than 50 years | Diagnostic test | Conventional screening |
| Annual digital rectal exam and PSA determinationFor Prostate Screening: Man older than 50 years | Diagnostic test | Enhanced screening |
| Annual appointment for low dose computed tomography for lung screeningFor Lung Screening: should accomplish ALL the following criteria: * Age > 40 years * Active smoker or former smoker<3 years, with IPY ≥20. IPY: index of packages-year: nº packages that smoke per day x nº years smoking * No contraindications for thoracic surgery * No lung infection in the last 2 months | Diagnostic test | Enhanced screening |
| Annual general inspection for skin lesions suggestive of malignancyFor Skin Screening: Woman ≥18 years Man ≥40 years | Diagnostic test | Enhanced screening |
Primary outcome
Non-AIDS defining cancers incidence
Time frame: through study completion, an average of 1 year
The incidence of different neoplasms not considered as AIDS defining cancers compared between two arms
Survival rate
Time frame: through study completion, an average of 1 year
Comparison in survival terms between conventional and enhanced screening arms
2 secondary outcomes
Safety of the screening: adverse events
Time frame: through study completion, an average of 1 year
Cost-efectiveness
Time frame: through study completion, an average of 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2021.
- Results publication: PubMed 26093959Lopez C, Masia M, Padilla S, Aquilino A, Bas C, Gutierrez F. [Deaths due to non-AIDS diseases among HIV infected patients: A 14-year study (1998-2011)]. Enferm Infecc Microbiol Clin. 2016 Apr;34(4):222-7. doi: 10.1016/j.eimc.2015.04.010. Epub 2015 Jun 18. Spanish.
- Results publication: PubMed 30679001Garcia-Abellan J, Del Rio L, Garcia JA, Padilla S, Vivancos MJ, Del Romero J, Asensi V, Hernando A, Garcia-Fraile L, Masia M, Gutierrez F; la Cohorte de la Red Nacional de Sida (CoRIS). Risk of cancer in HIV-infected patients in Spain, 2004-2015. The CoRIS cohort study. Enferm Infecc Microbiol Clin (Engl Ed). 2019 Oct;37(8):502-508. doi: 10.1016/j.eimc.2018.11.011. Epub 2019 Jan 22. English, Spanish.
- Results publication: PubMed 25042234Smith 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.
- Results publication: PubMed 19770804Shiels MS, Cole SR, Kirk GD, Poole C. A meta-analysis of the incidence of non-AIDS cancers in HIV-infected individuals. J Acquir Immune Defic Syndr. 2009 Dec;52(5):611-22. doi: 10.1097/QAI.0b013e3181b327ca.
- Results publication: PubMed 17617273Grulich AE, van Leeuwen MT, Falster MO, Vajdic CM. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet. 2007 Jul 7;370(9581):59-67. doi: 10.1016/S0140-6736(07)61050-2.
- Results publication: PubMed 25362204Althoff KN, McGinnis KA, Wyatt CM, Freiberg MS, Gilbert C, Oursler KK, Rimland D, Rodriguez-Barradas MC, Dubrow R, Park LS, Skanderson M, Shiels MS, Gange SJ, Gebo KA, Justice AC; Veterans Aging Cohort Study (VACS). Comparison of risk and age at diagnosis of myocardial infarction, end-stage renal disease, and non-AIDS-defining cancer in HIV-infected versus uninfected adults. Clin Infect Dis. 2015 Feb 15;60(4):627-38. doi: 10.1093/cid/ciu869. Epub 2014 Oct 30.
- Results publication: PubMed 25294086Cobucci RN, Lima PH, de Souza PC, Costa VV, Cornetta Mda C, Fernandes JV, Goncalves AK. Assessing the impact of HAART on the incidence of defining and non-defining AIDS cancers among patients with HIV/AIDS: a systematic review. J Infect Public Health. 2015 Jan-Feb;8(1):1-10. doi: 10.1016/j.jiph.2014.08.003. Epub 2014 Oct 5.
- Results publication: PubMed 23018442Masia M, Padilla S, Alvarez D, Lopez JC, Santos I, Soriano V, Hernandez-Quero J, Santos J, Tural C, del Amo J, Gutierrez F; CoRIS. Risk, predictors, and mortality associated with non-AIDS events in newly diagnosed HIV-infected patients: role of antiretroviral therapy. AIDS. 2013 Jan 14;27(2):181-9. doi: 10.1097/QAD.0b013e32835a1156.
- Results publication: PubMed 18490686Patel P, Hanson DL, Sullivan PS, Novak RM, Moorman AC, Tong TC, Holmberg SD, Brooks JT; Adult and Adolescent Spectrum of Disease Project and HIV Outpatient Study Investigators. Incidence of types of cancer among HIV-infected persons compared with the general population in the United States, 1992-2003. Ann Intern Med. 2008 May 20;148(10):728-36. doi: 10.7326/0003-4819-148-10-200805200-00005.
- Results publication: PubMed 27749369Shiels MS, Engels EA. Evolving epidemiology of HIV-associated malignancies. Curr Opin HIV AIDS. 2017 Jan;12(1):6-11. doi: 10.1097/COH.0000000000000327.
- Results publication: PubMed 29249478Croxford S, Kitching A, Desai S, Kall M, Edelstein M, Skingsley A, Burns F, Copas A, Brown AE, Sullivan AK, Delpech V. Mortality and causes of death in people diagnosed with HIV in the era of highly active antiretroviral therapy compared with the general population: an analysis of a national observational cohort. Lancet Public Health. 2017 Jan;2(1):e35-e46. doi: 10.1016/S2468-2667(16)30020-2. Epub 2016 Dec 15.
- Results publication: PubMed 29642182Wang YH, Shen XD. Human immunodeficiency virus infection and mortality risk among lung cancer patients: A systematic review and meta-analysis. Medicine (Baltimore). 2018 Apr;97(15):e0361. doi: 10.1097/MD.0000000000010361.
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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.
Félix Gutiérrez-Rodero, PhD principal investigator
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Digital rectal exam and / or anal cytology (day 1 and after 36 months), Semestral digital rectal exam and / or anal cytology if abnormal → ANOSCOPY with biopsy and Cervical cytology and cervical sample for HPV detection (day 1 and after 36 months) in people with HIV/AIDS and Cancer, run by Felix Gutierrez at 1 site in Spain.
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 5 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 3 Feb 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 Spain. 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.
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 Sergio Padilla-Urrea, PhD (+34 966616234, padilla_ser@gva.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Non-AIDS defining cancers incidence (time frame: through study completion, an average of 1 year). 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?
On the ClinicalTrials.gov record for NCT04735445, which also lists 19 linked publications.
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 3 Feb 2021.