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Trial record 2 of 3 for:    17135583 [PUBMED-IDS]

Monitored Antiretroviral Pause in Chronic HIV-Infected Subjects With Long-Lasting Suppressed Viremia (APACHE)

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ClinicalTrials.gov Identifier: NCT03198325
Recruitment Status : Recruiting
First Posted : June 26, 2017
Last Update Posted : June 26, 2017
Sponsor:
Information provided by (Responsible Party):
Castagna Antonella, Ospedale San Raffaele

Brief Summary:

Prospective, open-label, single arm, non-randomized, proof-of-concept study. Eligible patients will sign a written informed consent and will be followed-up at screening, baseline (ART interruption) and at 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption.

The study visits will include: general clinical assessment, routine laboratory tests including: creatinine, phosphorus, calcium, alkaline phosphatase, AST, ALT, fasting glucose, total cholesterol, HDL- and LDL-cholesterol, triglycerides, CD4+ cell count and CD4+/CD8+ ratio.

Additional 30 mL of peripheral blood will be withdrawn at study visits for further virological, and immunological investigations and for bio-banking purposes.

During follow-up, the occurrence of two consecutive HIV-1 RNA values >50 copies/mL or the occurrence of stage B or C AIDS-defining events or any serious non-AIDS clinical event at least potentially related to treatment interruption will be criteria for ART resumption.

All patients with HIV-RNA<50 copies/mL at week 48 (end of the study) will resume their baseline ART regimen.

The main demographic, clinical and therapy information will be accurately recorded at the study visits in an electronic Case Report Form.


Condition or disease Intervention/treatment Phase
HIV Seropositivity Other: Stop of ART Not Applicable

Detailed Description:

The aim of this proof-of-concept study on adult (>18 and <65 years old), chronically HIV-1 infected individuals with undetectable viremia for ≥10 years, undetectable HIV-DNA, CD4+≥500 cells/µL and no evidence of detectable residual viremia for ≥5 years is to evaluate the frequency of spontaneous control of virus replication after ART pausing for up to 12 months and to identify the virological and immunological markers associated with spontaneous control of viral replication.

Prospective, open-label, single arm, non-randomized, proof-of-concept study.

Eligible patients will sign a written informed consent and will be followed-up at screening, baseline (ART interruption) and at 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption.

The clinical assessment (study visit) will include: the evaluation of CDC stage, height, weight, systolic and diastolic blood pressure and smoking status, routine laboratory tests [including creatinine, phosphorus, calcium, alkaline phosphatase, AST, ALT, fasting glucose, total cholesterol, HDL- and LDL-cholesterol, triglycerides, CD4+ cell count and CD4+/CD8+ ratio, urine analysis].

Additional 30 mL of peripheral blood will be withdrawn at study visits and stored in a biobank for further investigations.

During follow-up, the occurrence of two consecutive HIV-1 RNA values >50 copies/mL or the occurrence of stage B or C AIDS-defining events will be criteria for ART resumption or any serious non-AIDS clinical event at least potentially related to treatment interruption.

All patients with HIV-RNA<50 copies/mL at week 48 (end of the study) will resume their baseline ART regimen.

The main demographic, clinical and therapy information will be accurately recorded at the study visits in an electronic Case Report Form (eCRF).


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Monitored Antiretroviral Pause in Chronic HIV-Infected Subjects With Long-Lasting Suppressed Viremia (APACHE Study)
Actual Study Start Date : July 27, 2016
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : April 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Interruption of antiretroviral therapy
Patients willing to stop antiretroviral therapy will stop ART.The occurrence of two consecutive HIV-1 RNA values >50 copies/mL or the occurrence of stage B or C AIDS-defining events will be criteria for ART resumption or any serious non-AIDS clinical event at least potentially related to treatment interruption.
Other: Stop of ART
Patients willing to stop antiretroviral therapy will stop ART.The occurrence of two consecutive HIV-1 RNA values >50 copies/mL or the occurrence of stage B or C AIDS-defining events will be criteria for ART resumption or any serious non-AIDS clinical event at least potentially related to treatment interruption.




Primary Outcome Measures :
  1. Patients who will not resume antiretroviral regimen [ Time Frame: 12 month ]
    Cumulative proportion of patients who will not resume ART 12 months after IMAP (Monitored Antiretroviral Pause) due to the occurrence of two consecutive HIV-1 RNA values >50 copies/mL or the occurrence of stage B or C AIDS-defining events or any serious non-AIDS clinical event at least potentially related to treatment interruption.


Secondary Outcome Measures :
  1. Change in plasma viremia [ Time Frame: 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption. ]
    Change in plasma viremia

  2. Change in plasma HIV-DNA [ Time Frame: 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption. ]
    Change in plasma HIV-DNA

  3. Change in CD4+ [ Time Frame: 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption. ]
    Change in CD4+

  4. Change in CD4+/CD8+ ratio [ Time Frame: 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption. ]
    Change in CD4+/CD8+ ratio

  5. Change in virological biomarkers [ Time Frame: 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption. ]
    Change in virological biomarkers prior to ART interruption and/or at ART resumption

  6. Change in immunological biomarkers [ Time Frame: 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption. ]
    Change in immunological biomarkers prior to ART interruption and/or at ART resumption



Information from the National Library of Medicine

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 to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

The study will include HIV-1 infected:

  • men and non-pregnant women,
  • ≥18 and <65 years-old,
  • asking to stop therapy,
  • with HIV-1 RNA<50 copies/mL for ≥10 years,
  • current CD4+≥500 cells/µL,
  • HIV-DNA<100 copies/106PBMCs,
  • no evidence of detectable residual viremia for ≥5 years .

Exclusion Criteria:

The study will exclude HIV-1 infected subjects:

  • significant risk of HIV transmission during IMAP (including evidence of not adopting effective contraception methods and women who wish to be pregnant) in the opinion of the investigator,
  • pregnancy and breastfeeding,
  • a documented pre-ART HIV-1 RNA<200 copies/mL,
  • reactive Hepatitis B virus (HBV) surface antigen,
  • positive HCV-RNA at the time of screening,
  • current AIDS defining event as defined in category C of the 'Centers for disease control and prevention (CDC)' clinical classification,
  • previous diagnosis of diabetes,
  • a previous diagnosis of cancer or major adverse cardiac events (MACE) and currently receiving chemotherapy or immuno-modulating agents at the time of screening,
  • history of HIV-related thrombocytopenia,
  • active renal disease defined as a glomerular filtration rate (calculated by MDRD equation) below 50 mL/min or the presence of HIV associated nephropathy in the past medical history,
  • any condition, including psychiatric or psychological disorders that might interfere with adherence to study requirements or safety of the participant,
  • prior use of any HIV vaccine and/or non-established experimental therapy,
  • active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.

Information from the National Library of Medicine

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): NCT03198325


Contacts
Contact: Antonella Castagna, Professor 00390226437934 castagna.antonella1@hsr.it
Contact: Elisabetta Carini, MD 00390226437934 carini.elisabetta@hsr.it

Locations
Italy
Ospedale San Raffaele Scientific Institute Recruiting
Milan, Italy, 20127
Contact: Elisabetta Carini    0039022643 ext 7934    carini.elisabetta@hsr.it   
Sponsors and Collaborators
Ospedale San Raffaele

Publications:

Responsible Party: Castagna Antonella, Professor, Ospedale San Raffaele
ClinicalTrials.gov Identifier: NCT03198325     History of Changes
Other Study ID Numbers: APACHE Study
First Posted: June 26, 2017    Key Record Dates
Last Update Posted: June 26, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Congress and scientific pubblications

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Castagna Antonella, Ospedale San Raffaele:
HIV-1

Additional relevant MeSH terms:
Viremia
HIV Seropositivity
Virus Diseases
Sepsis
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases