HIV-1 InfectionPhase 2NCT02155985

Modulation of Immune Activation by Aspirin

A Phase 2 study testing Aspirin in people with HIV-1 Infection, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 15 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: HIV-1 Infection
What is being tested?: Aspirin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 121 participants
Where: 15 sitesUnited States
Study dates: Aug 2014to Jul 2015
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

HIV-1 infection.
Currently on continuous ART for ≥48 weeks prior to study entry. NOTE: This is defined as continuous active therapy with no treatment interruption longer than 7 consecutive days and a total duration off-treatment of no more than 14 days during the 48 weeks prior to entry.
No change in ART regimen within the 12 weeks prior to study entry (except as noted below).
NOTE: Modifications of ART dosing during within the 12 weeks prior to entry are permitted. In addition, the change in formulation (eg, from standard formulation to fixed dose combination or single tablet regimen) or dosing (eg, from once a day to twice a day) is allowed within 12 weeks prior to entry. Within-class single drug substitution (eg, switch from nevirapine to efavirenz or from atazanavir to darunavir), are not allowed within 12 weeks prior to entry. No other changes in ART in the 12 weeks prior to entry are permitted.
Screening HIV-1 RNA must be <50 copies/mL and performed by any FDA-approved assay at any US laboratory that has a CLIA certification or its equivalent within 45 days prior to study entry.
Maintain ART-mediated viral suppression for at least 48 weeks prior to study entry defined as:

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At least one HIV-1 RNA test result obtained at any time point greater than 48 weeks prior to study entry must be BLQ and must be performed by any FDA-approved assay at a CLIA-certified laboratory or its equivalent.
AND
All HIV-1 RNA tests reported during the 48 weeks prior to study entry must be BLQ and must be performed by any FDA-approved assay at a CLIA-certified laboratory or its equivalent.
NOTE: A single RNA "blip" of ≤500 copies/mL is permissible if RNA levels most recent before and after (may include the screening HIV-1 RNA test) are below the level of quantification (BLQ) for the assay. If the RNA level after the blip is the screening HIV-1 RNA test, the result must be <50 copies/mL.
The following laboratory values obtained within 45 days prior to study entry by any US laboratory that has a CLIA certification or its equivalent.
Absolute neutrophil count (ANC) ≥750/mm^3
Hemoglobin ≥9.0 g/dL for female subjects and ≥10.0 g/dL for male subjects
Platelet count >100,000/mm^3
Prothrombin time (PT) <1.2 x upper limit normal (ULN)
Partial thromboplastin time (PTT) <1.5 x ULN
Calculated creatinine clearance (CrCl) ≥30 mL/min, as estimated by the Cockroft-Gault formula NOTE: Calculation for the Cockcroft-Gault equation is available at https://www.fstrf.org/apps/cfmx/apps/common/Portal/index.cfm
Aspartate aminotransferase (AST) (SGOT) ≤2 x ULN.
Alanine aminotransferase (ALT) (SGPT) ≤2 x ULN.
Alkaline phosphatase ≤2 x ULN.
Total bilirubin ≤2.5 x ULN. If the subject if taking an indinavir- or atazanavir-containing regimen at the time of screening, a total bilirubin of ≤5 x ULN is acceptable.
Female study volunteers of reproductive potential (pre-menopausal women who have not had a sterilization procedure (eg, hysterectomy, bilateral oophorectomy, tubal ligation, or salpingectomy) must have a negative serum or urine pregnancy test performed within 24 hours prior to study entry. Women are considered menopausal if they have not had a menses for at least 12 months and have a FSH (follicle stimulating hormone) of greater than 40 IU/L or, if FSH testing is not available, they have had amenorrhea for 24 consecutive months.
If the female volunteer is not of reproductive potential (women who are menopausal, defined as not having had a menses for at least 12 months with an FSH of greater than 40 IU/L, or if FSH testing is not available, have had amenorrhea for 24 consecutive months, or women who have undergone surgical sterilization, (eg, hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy)), she is eligible without requiring the use of a contraceptive method. Acceptable documentation of sterilization is subject reported history of hysterectomy, bilateral oophorectomy, tubal ligation, tubal micro-insert, menopause, or the partner with vasectomy/azoospermia.
If participating in sexual activity that could lead to pregnancy, the female study volunteer must be willing to use contraception while receiving protocol-specified medication(s) and for the washout period of 4 weeks. At least one of the following methods MUST be used:
Condoms (male or female), with or without a spermicidal agent
Diaphragm or cervical cap with spermicide
Intrauterine device (IUD)
Hormone-based contraceptive
As hormone-based contraceptives (oral, transdermal, or subdermal) can affect coagulopathy biomarkers, subjects who plan on using such a contraceptive during the study must be taking the same product for ≥4 weeks prior to screening and be encouraged to continue throughout the duration of the study, if medically feasible.
No documented opportunistic infections within 24 weeks prior to study entry
Karnofsky performance score >/= 70 within 45 days prior to study entry
Ability and willingness of subject or legal guardian/representative to provide written informed consent.
Willingness to refrain from the use of aspirin or any aspirin-related product (other than the study drug), including NSAIDs, from time of screening visit through the end of the 16 week trial.
NOTE: Acetaminophen-based products may be used before and during the trial when analgesics are required.
Completion of the pre-entry FMD assessment NOTE: The FMD must be performed at the site and confirmed as acceptable by the University of Wisconsin Atherosclerosis Imaging Research Program (UW AIRP) core lab prior to study entry.
Confirmation of the availability of the stored pre-entry fasting specimens (plasma and serum); the site must confirm that these specimens have been entered into the Laboratory Data Management System (LDMS).

Who cannot join

Current malignancy (except non-melanoma cancer of the skin not requiring systemic chemotherapy or radiation therapy).
NOTE: Carcinoma in situ of the cervix or anus is not considered exclusionary.
Prior history of malignancy if the subject is not disease free for 24 or more weeks prior to study entry.
Current use or indication for use of non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin that cannot be interrupted for clinical reasons. Examples of clinical reasons include, but are not limited to, known and documented cardiovascular disease (history of MI, coronary artery bypass graft surgery, percutaneous coronary intervention, stroke, transient ischemic attack, peripheral arterial disease with ABI <0.9 or claudication).
Current diagnosis of diabetes with HbA1c ≥8% within 24 weeks prior to screening.
Changes in lipid-lowering or antihypertensive medication within 90 days prior to study entry or expected need to modify these medications during the study.

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NOTE: Lipid-lowering medication includes: statins, fibrates, niacin (dose ≥250 mg daily), and fish-oil/omega 3 fatty acids (dose >1000 mg of marine oils daily).
Known cirrhosis
Known chronic active hepatitis B NOTE: Active hepatitis B is defined as hepatitis B surface antigen positive and hepatitis B DNA positive within 24 weeks prior to study entry; subjects with hepatitis B virus (HBV) DNA BLQ for greater than 24 weeks prior to study entry are eligible.
Known chronic active hepatitis C NOTE: Active hepatitis C is defined as a detectable plasma HCV RNA level within 24 weeks prior to study entry; subjects with HCV RNA BLQ for greater than 24 weeks prior to study entry are eligible.
Known inflammatory conditions, such as, but not limited to, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), sarcoidosis, inflammatory bowel disease (IBD), chronic pancreatitis, autoimmune hepatitis, Adult Stills disease, Rheumatic heart disease, bursitis.
Breastfeeding or pregnant
Previous intolerance or allergy to aspirin or any aspirin products.
Frequent use of aspirin or aspirin products (NSAIDs), defined as an average of 2 or more times per week in the last 12 weeks prior to study entry.
Immunosuppressant use, such as, but not limited to, systemic or potentially systemic glucocorticoids (including injected, ie, intra-articular, nasal or inhaled steroids), azathioprine, tacrolimus, mycophenolate, sirolimus, rapamycin, methotrexate, or cyclosporine within 45 days prior to study entry.
Use of any systemic antineoplastic or immunomodulatory treatment, investigational vaccines, interleukins, interferons, growth factors, or intravenous immunoglobulin (IVIG) within 45 days prior to study entry.
NOTE: Routine standard of care, including hepatitis A and/or B, human papilloma virus, influenza, pneumococcal, and tetanus vaccines are permitted if administered at least 7 days before study entry and before biomarker/peripheral blood mononuclear cell (PBMC) blood collections.
Concurrent use of prohibited medications as per section 5.4
Heavy alcohol use as defined by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) http://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/moderate-binge-drinking
Alcohol or drug use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
Current use of anticoagulation therapy or conditions requiring use of anticoagulants, use such as, but not limited to warfarin (Coumadin), rivaroxaban (Xarelto), clopidogrel (Plavix), dabigatran (Pradaxa), apixaban (Eliquis), heparin, ticlopidine (Ticlid), Presugrel (Effient).
History of coagulopathy, deep venous thrombosis, pulmonary embolism.
Known active or recent (not fully resolved within 4 weeks prior to study entry) invasive bacterial, fungal, parasitic, or viral infections.
NOTE: Recurrent herpes simplex virus (HSV) is not exclusionary. Subjects on antiviral prophylaxis for HSV or VZV are encouraged to remain on treatment for the duration of the study if medically feasible.
Serious illness or trauma requiring systemic treatment and/or hospitalization within 4 weeks prior to study entry.
History of bleeding conditions such as peptic ulcer disease, hemophilia, von Willebrand disease, idiopathic thrombocytopenic purpura.
History of thrombotic disorders such as protein C or S deficiency.
History of gastrointestinal (GI) bleeding within the past 6 months prior to study entry.
History of intracranial hemorrhage.

Trial locations and contacts

15 sites in 1 country.

City, postcode or hospital

15 sites in 1 country

United States15 sites

University of Colorado Hospital CRS (6101)
Aurora, Colorado, 80045
Massachusetts General Hospital ACTG CRS (101)
Boston, Massachusetts, 02114
Brigham and Women's Hosp. ACTG CRS (107)
Boston, Massachusetts, 02115
3201 Chapel Hill CRS
Chapel Hill, North Carolina, 27516
2701 Northwestern University CRS
Chicago, Illinois, 60611
Rush Univ. Med. Ctr. ACTG CRS (2702)
Chicago, Illinois, 60612
Univ. of Cincinnati CRS (2401)
Cincinnati, Ohio, 45267
Case CRS (2501)
Cleveland, Ohio, 44106
Greensboro CRS (3203)
Greensboro, North Carolina, 27401
Houston AIDS Research Team CRS (31473)
Houston, Texas, 77030
601 University of California, Los Angeles CARE Center CRS
Los Angeles, California, 90035
3652 Vanderbilt Therapeutics (VT) CRS
Nashville, Tennessee, 37204
701 University of California, San Diego AntiViral Research Center CRS
San Diego, California, 92103
Ucsf Aids Crs (801)
San Francisco, California, 94110
Harbor-UCLA Med. Ctr. CRS (603)
Torrance, California, 90502

Other trials in United States

About this study

Since people started taking HIV medications, illness from AIDS has decreased, but other serious diseases like heart disease, cancer, and kidney, and liver disease have increased. HIV causes inflammation (irritation) inside the body that cannot be felt but can be measured by blood. Inflammation can lead to diseases that have become some of the leading causes of death in people with HIV. HIV therapy can partially lower levels of inflammation measured in blood, however, levels of inflammation in people who have HIV may remain high compared with people not infected with HIV.

Aspirin is a drug that is commonly used for pain relief but is also approved by the Food and Drug Administration (FDA) for preventing heart attacks and stroke in those who are at increased risk for heart attack and stroke. Aspirin also is used (but is not approved by the FDA) to decrease the risk of some cancers in people who are at increased risk. Aspirin is thought to decrease risk of heart attack and stroke because it blocks the activation of platelets and prevents blood clots from clogging narrowed blood vessels, a disease called atherosclerosis. It is unknown how aspirin might decrease the chance of developing cancer in some people at higher risk, but aspirin has been shown to modulate (or change) the immune system. In HIV-infected people who have been taking antiretroviral therapy and have an undetectable HIV viral load it was recently shown that low-dose aspirin 81 mg (baby aspirin), given for one week, lowers platelet activation and reduces blood markers of inflammation which may improve the function of the immune system.

The purpose of this study was to evaluate whether aspirin improves inflammation and immune activation when compared to a placebo (inactive medication like a dummy pill) and to determine if 12 weeks of aspirin 300 mg and aspirin 100 mg is safe for HIV-infected persons on antiretroviral therapy. Additionally, it studied whether a higher dose and longer duration of aspirin provides further anti-inflammatory and immune-modulating benefit. This was done using blood and urine tests that measure inflammation and also with a test that uses ultrasound to measure the flow of blood in your arm, called flow-mediated vasodilation (FMD) of the brachial artery (BART). This is a painless test that bounces sound waves off of a blood vessel in your arm.

Read the detailed description

This was a phase II prospective, double-blind, randomized, placebo-controlled 3-arm clinical trial to study whether aspirin improves inflammation and immune activation. At study entry, participants were randomized between the three study arms: aspirin 300 mg, aspirin 100 mg and placebo. The study treatment duration was 12 weeks, followed by a 4 week washout period. The study duration was 16 weeks.

The study clinic visits included pre-entry (within 7 days prior to entry), entry, on treatment visits at weeks 2, 11 and 12, and final study visit at the end of the wash-out period at week 16. The samples for the primary and secondary outcomes were collected at pre-entry, entry, and weeks 2, 11 and 12. The evaluations of safety (clinical assessment for signs and symptoms, diagnoses, laboratory tests) were done at entry and weeks 2, 11, 12 and 16.

The co-primary objectives used pair-wise comparisons to assess the effects of 300 mg and 100 mg of daily aspirin for 12 weeks on plasma sCD14 levels.

Conditions: HIV-1 Infection
Being tested: Aspirin, Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AspirinDrug
Aspirin is a nonsteroidal antiinflammatory drug (NSAID) effective in treating fever, pain, and inflammation in the body.
PlaceboDrug
Placebo for aspirin

Study groups in NCT02155985
Study group	Role	What they receive
Aspirin 300 mg + aspirin 100 mg placebo	Active comparator	At week 0, participants were prescribed aspirin 300 mg (one tablet) and placebo for aspirin 100 mg (one tablet) once daily. At week 12, participants were to stop both study product tablets to allow for a 4-week washout period. Receives: Drug: Aspirin; Drug: Placebo
Aspirin 100 mg + aspirin 300 mg placebo	Active comparator	At week 0, participants were prescribed a placebo for aspirin 300 mg (one tablet) and aspirin 100 mg (one tablet) once daily. At week 12, participants were to stop both study product tablets to allow for a 4-week washout period. Receives: Drug: Aspirin; Drug: Placebo
Aspirin 300 mg + aspirin 100 mg placebos	Placebo comparator	At week 0, participants were prescribed a placebo for aspirin 300 mg (one tablet) and placebo for aspirin 100 mg (one tablet) once daily. At week 12, participants were to stop both study products tablets to allow for a 4-week washout period. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in sCD14 From Baseline to Week 11/12
Baseline is defined as the average of the Pre-Entry and Entry values. Week 11/12 is defined as the average of the Week 11 and Week 12 values. All values were log10 transformed prior to calculating change and conducting analyses. Values obtained within 6 days after the influenza vaccination were excluded.
Absolute change was calculated as the value at week 11/12 minus the value at baseline. Mean changes were exponentiated to be back on the untransformed scale and corresponds to a mean fold change. Differences between arms are expressed as the percent difference between mean fold changes.
Measured: Pre-entry and entry to weeks 11 and 12

Secondary outcomes (19)

Safety
Safety was summarized as the highest grade sign/symptom, laboratory event, or diagnosis per participant.
Grading (Grade 0: normal, Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening) was done by site clinicians using DAIDS AE Grading table.
Measured: After study entry to Week 16
Tolerability
Tolerability was summarized as the number of participants successfully completing the protocol-defined treatment period.
Measured: Treatment dispensation to Week 12
Change in sCD163 From Baseline to Week 11/12
Baseline is defined as the average of the Pre-Entry and Entry values. Week 11/12 is defined as the average of the Week 11 and Week 12 values. All values were log10 transformed prior to calculating change and conducting analyses. Values obtained within 6 days after the influenza vaccination were excluded.
Absolute change was calculated as the value at week 11/12 minus the value at baseline. Mean changes were exponentiated to be back on the untransformed scale and corresponds to a mean fold change.
Measured: Pre-entry and entry to weeks 11 and 12
Change in Expression of CD14dimCD16+ From Entry to Week 12
Absolute change was calculated as the value at week 12 minus the value at entry.
Measured: Entry to Week 12
Change in Expression of CD69+ on CD14dimCD16+ From Entry to Week 12
Absolute change was calculated as the value at week 12 minus the value at entry.
Measured: Entry to Week 12
Change in Expression of CD14+CD16- From Entry to Week 12
Absolute change was calculated as the value at week 12 minus the value at entry.
Measured: Entry to Week 12
Change in Expression of CD69+ on CD14+CD16- From Entry to Week 12
Absolute change was calculated as the value at week 12 minus the value at entry.
Measured: Entry to Week 12
Change in Expression of CD14+CD16+ From Entry to Week 12
Absolute change was calculated as the value at week 12 minus the value at entry.
Measured: Entry to Week 12
Change in Expression of CD69+ on CD14+CD16+ From Entry to Week 12
Absolute change was calculated as the value at week 12 minus the value at entry.
Measured: Entry to Week 12
Change in Expression of CD38+HLA-DR+ on CD4+ From Entry to Week 12
Absolute change was calculated as the value at week 12 minus the value at entry.
Measured: Entry to Week 12
Change in Expression of CD38+HLA-DR+ on CD8+ From Entry to Week 12
Absolute change was calculated as the value at week 12 minus the value at entry.
Measured: Entry to Week 12
Change in Expression of PD-1+ on CD4+ From Entry to Week 12
Absolute change was calculated as the value at week 12 minus the value at entry.
Measured: Entry to Week 12
Change in Expression of PD-1+ on CD8+ From Entry to Week 12
Absolute change was calculated as the value at week 12 minus the value at entry.
Measured: Entry to Week 12
Change in IL-6 From Baseline to Week 11/12
Baseline is defined as the average of the Pre-Entry and Entry values. Week 11/12 is defined as the average of the Week 11 and Week 12 values. All values were log10 transformed prior to calculating change and conducting analyses. Values obtained within 6 days after the influenza vaccination were excluded.
Absolute change was calculated as the value at week 11/12 minus the value at baseline. Mean changes were exponentiated to be back on the untransformed scale and corresponds to a mean fold change.
Measured: Pre-entry and entry to weeks 11 and 12
Change in D-dimer From Baseline to Week 11/12
Baseline is defined as the average of the Pre-Entry and Entry values. Week 11/12 is defined as the average of the Week 11 and Week 12 values. All values were log10 transformed prior to calculating change and conducting analyses. Values obtained within 6 days after the influenza vaccination were excluded.
Absolute change was calculated as the value at week 11/12 minus the value at baseline. Mean changes were exponentiated to be back on the untransformed scale and corresponds to a mean fold change.
Measured: Pre-entry and entry to weeks 11 and 12
Change in Kynurenine to Tryptophan Ratio From Entry to Week 12
Absolute change was calculated as the value at week 12 minus the value at entry.
Measured: Entry to Week 12
Change in Serum Thromboxane B2 From Entry to Week 12
Absolute change was calculated as the value at week 12 minus the value at entry.
Measured: Entry to Week 12
Change in Urine Thromboxane Per Creatinine From Entry to Week 12
Absolute change was calculated as the value at week 12 minus the value at entry.
Measured: Entry to Week 12
Change in Brachial Artery Flow-mediated Dilation (FMD) From Entry to Week 12
Absolute change was calculated as the value at week 12 minus the value at entry.
Measured: Entry to Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2014Jul 2015

First posted4 Jun 2014 (estimated)
Study startAug 2014
Primary completionJun 2015
Study completionJul 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HIV-1 InfectionStudies 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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Care provider
Enrolment: 121 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02155985
Sponsor's protocol ID: ACTG A5331
Other IDs: UM1AI068636
Status last verified: May 2017
First submitted: 3 Jun 2014
Last updated: 12 Jun 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 12 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Modulation of Immune Activation by Aspirin
ClinicalTrials.gov ID: NCT02155985
Acronym / sponsor ID: ACTG A5331
Conditions: HIV-1 Infection
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 121 participants (actual)
Lead sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other InfectionsResearch network
Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
Study start: Aug 2014
Primary completion: Jun 2015 (actual)
Study completion: Jul 2015 (actual)
First posted: 4 Jun 2014 (estimated)
Results: Posted 7 Jul 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

The co-primary objectives used pair-wise comparisons to assess the effects of 300 mg and 100 mg of daily aspirin for 12 weeks on plasma sCD14 levels.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, care provider)
Number of arms: 3

Arm	Type	Receives
Aspirin 300 mg + aspirin 100 mg placebo	Active comparator	Drug: Aspirin, Drug: PlaceboAt week 0, participants were prescribed aspirin 300 mg (one tablet) and placebo for aspirin 100 mg (one tablet) once daily. At week 12, participants were to stop both study product tablets to allow for a 4-week washout period.
Aspirin 100 mg + aspirin 300 mg placebo	Active comparator	Drug: Aspirin, Drug: PlaceboAt week 0, participants were prescribed a placebo for aspirin 300 mg (one tablet) and aspirin 100 mg (one tablet) once daily. At week 12, participants were to stop both study product tablets to allow for a 4-week washout period.
Aspirin 300 mg + aspirin 100 mg placebos	Placebo comparator	Drug: PlaceboAt week 0, participants were prescribed a placebo for aspirin 300 mg (one tablet) and placebo for aspirin 100 mg (one tablet) once daily. At week 12, participants were to stop both study products tablets to allow for a 4-week washout period.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (36 listed)

HIV-1 infection.
Currently on continuous ART for ≥48 weeks prior to study entry. NOTE: This is defined as continuous active therapy with no treatment interruption longer than 7 consecutive days and a total duration off-treatment of no more than 14 days during the 48 weeks prior to entry.
No change in ART regimen within the 12 weeks prior to study entry (except as noted below).
NOTE: Modifications of ART dosing during within the 12 weeks prior to entry are permitted. In addition, the change in formulation (eg, from standard formulation to fixed dose combination or single tablet regimen) or dosing (eg, from once a day to twice a day) is allowed within 12 weeks prior to entry. Within-class single drug substitution (eg, switch from nevirapine to efavirenz or from atazanavir to darunavir), are not allowed within 12 weeks prior to entry. No other changes in ART in the 12 weeks prior to entry are permitted.
Screening HIV-1 RNA must be <50 copies/mL and performed by any FDA-approved assay at any US laboratory that has a CLIA certification or its equivalent within 45 days prior to study entry.

Key exclusion criteria (29 listed)

Current malignancy (except non-melanoma cancer of the skin not requiring systemic chemotherapy or radiation therapy).
NOTE: Carcinoma in situ of the cervix or anus is not considered exclusionary.
Prior history of malignancy if the subject is not disease free for 24 or more weeks prior to study entry.
Current use or indication for use of non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin that cannot be interrupted for clinical reasons. Examples of clinical reasons include, but are not limited to, known and documented cardiovascular disease (history of MI, coronary artery bypass graft surgery, percutaneous coronary intervention, stroke, transient ischemic attack, peripheral arterial disease with ABI <0.9 or claudication).
Current diagnosis of diabetes with HbA1c ≥8% within 24 weeks prior to screening.

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
AspirinAspirin is a nonsteroidal antiinflammatory drug (NSAID) effective in treating fever, pain, and inflammation in the body.	Drug	Aspirin 100 mg + aspirin 300 mg placebo, Aspirin 300 mg + aspirin 100 mg placebo
PlaceboPlacebo for aspirin	Drug	Aspirin 100 mg + aspirin 300 mg placebo, Aspirin 300 mg + aspirin 100 mg placebo, Aspirin 300 mg + aspirin 100 mg placebos

Primary outcome

Change in sCD14 From Baseline to Week 11/12
Time frame: Pre-entry and entry to weeks 11 and 12
Baseline is defined as the average of the Pre-Entry and Entry values. Week 11/12 is defined as the average of the Week 11 and Week 12 values. All values were log10 transformed prior to calculating change and conducting analyses. Values obtained within 6 days after the influenza vaccination were excluded. Absolute change was calculated as the value at week 11/12 minus the value at baseline. Mean changes were exponentiated to be back on the untransformed scale and corresponds to a mean fold change. Differences between arms are expressed as the percent difference between mean fold changes.

19 secondary outcomes

Safety
Time frame: After study entry to Week 16
Tolerability
Time frame: Treatment dispensation to Week 12
Change in sCD163 From Baseline to Week 11/12
Time frame: Pre-entry and entry to weeks 11 and 12
Change in Expression of CD14dimCD16+ From Entry to Week 12
Time frame: Entry to Week 12
Change in Expression of CD69+ on CD14dimCD16+ From Entry to Week 12
Time frame: Entry to Week 12
Change in Expression of CD14+CD16- From Entry to Week 12
Time frame: Entry to Week 12
Change in Expression of CD69+ on CD14+CD16- From Entry to Week 12
Time frame: Entry to Week 12
Change in Expression of CD14+CD16+ From Entry to Week 12
Time frame: Entry to Week 12
Change in Expression of CD69+ on CD14+CD16+ From Entry to Week 12
Time frame: Entry to Week 12
Change in Expression of CD38+HLA-DR+ on CD4+ From Entry to Week 12
Time frame: Entry to Week 12
Change in Expression of CD38+HLA-DR+ on CD8+ From Entry to Week 12
Time frame: Entry to Week 12
Change in Expression of PD-1+ on CD4+ From Entry to Week 12
Time frame: Entry to Week 12
Change in Expression of PD-1+ on CD8+ From Entry to Week 12
Time frame: Entry to Week 12
Change in IL-6 From Baseline to Week 11/12
Time frame: Pre-entry and entry to weeks 11 and 12
Change in D-dimer From Baseline to Week 11/12
Time frame: Pre-entry and entry to weeks 11 and 12
Change in Kynurenine to Tryptophan Ratio From Entry to Week 12
Time frame: Entry to Week 12
Change in Serum Thromboxane B2 From Entry to Week 12
Time frame: Entry to Week 12
Change in Urine Thromboxane Per Creatinine From Entry to Week 12
Time frame: Entry to Week 12
Change in Brachial Artery Flow-mediated Dilation (FMD) From Entry to Week 12
Time frame: Entry to Week 12

Results and safety

Results posted to the registry on 7 Jul 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Aspirin 300 mg + Aspirin 100 mg Placebo	40	39
Aspirin 100 mg + Aspirin 300 mg Placebo	41	41
Aspirin 300 mg + Aspirin 100 mg Placebos	40	39

Primary outcome: Change in sCD14 From Baseline to Week 11/12

Time frame: Pre-entry and entry to weeks 11 and 12. Mean (95% Confidence Interval). Unit: fold change

Measure	Aspirin 300 mg + Aspirin 100 mg Placebo n = 38	Aspirin 100 mg + Aspirin 300 mg Placebo n = 38	Aspirin 300 mg + Aspirin 100 mg Placebos n = 36
Value	0.99 (0.94 to 1.04)	1.03 (0.98 to 1.08)	0.97 (0.93 to 1.02)

Aspirin 300 mg + Aspirin 100 mg Placebo vs Aspirin 300 mg + Aspirin 100 mg Placebos: Mean Difference (Net): 1.4 (95% CI -5.5 to 8.8), p = 0.70, t-test, 2 sided
Aspirin 100 mg + Aspirin 300 mg Placebo vs Aspirin 300 mg + Aspirin 100 mg Placebos: Mean Difference (Net): 5.5 (95% CI -1.7 to 13.3), p = 0.14, t-test, 2 sided

Population analysed: Analysis used the per-protocol population. Participants 1) without baseline AND week 11/12 sCD14 values, or 2) with premature discontinuation of study treatment, or 3) with a serious bacterial infection while on treatment, or 4) with \<70% self-reported adherence (based on all available days of recall) to study treatment were excluded.

19 secondary outcomes are reported in the full results.

Adverse events

Time frame: From baseline to Week 16.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Aspirin 300 mg + Aspirin 100 mg Placebo	0 of 40 (0%)	0 of 40 (0%)	0 of 40
Aspirin 100 mg + Aspirin 300 mg Placebo	0 of 41 (0%)	1 of 41 (2.4%)	0 of 41
Aspirin 300 mg + Aspirin 100 mg Placebos	0 of 40 (0%)	6 of 40 (15%)	0 of 40

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Version 2.0 of the DAIDS EAE ManualLink provided by the sponsor.
DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009),Link provided by the sponsor.

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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.

Judith A Aberg, MD study chair

Icahn School of Medicine at Mount Sinai

Meagan O'Brien, MD study chair

Icahn School of Medicine at Mount Sinai

15 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Aspirin in people with HIV-1 Infection, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 15 sites in United States.

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 36 inclusion and 29 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: finished, as of the sponsor's last update on 12 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 in sCD14 From Baseline to Week 11/12 (time frame: Pre-entry and entry to weeks 11 and 12). 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 NCT02155985.

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 12 Jun 2017.