Table 1. Clinical trials to reduce immune activation and vascular risk.
This table of completed and ongoing trials of immunomodulatory therapies or cardiovascular risk modifying drugs with anti-inflammatory effects includes only trials with subclinical vascular outcome measures. Trials of anti-inflammatory and anti-fibrotic drugs without vascular outcome measures are not included in this table but are discussed in the text.
| Intervention | Identifier | Population | Design | Size | Subclinical Vascular Outcome(s) | Status |
|---|---|---|---|---|---|---|
| Immunomodulatory Therapies | ||||||
| Methotrexate | NCT01949116 | >40yrs on ART with mod-high CVD risk | Placebo RCT | 200 | FMD | Recruiting |
| Tocilizumab (IL-6 receptor Ab) | NCT02049437 | 18-60yrs on ART with CD4 200-500 | Placebo crossover RCT | 36 | FMD; hyperemic VTI | Recruiting |
| Canakinumab (IL-1β Ab) | NCT02272946 | >40yrs on ART with high CVD risk | Placebo RCT | 110 | FMD; Aortic TBR | Not yet open |
| Pentoxifylline | NCT00864916 | >18yrs; all started ART at study entry | Placebo RCT | 26 | FMD | Completed[68] |
| Salsalate 4gm | NCT01046682 | >18yrs; on ART | Open label RCT | 40 | FMD | Completed[69] |
| Salsalate 3gm | N/A | >18yrs: NOT on ART | Single arm Open label | 11 | FMD | Completed[70] |
| CVD Risk Modifying Drugs with Anti-Inflammatory Effects | ||||||
| Rosuvastatin 10mg | NCT01218802 | >18yrs; on ART with LDL<130 and elevated hsCRP or CD8+ activation | Placebo RCT | 147 | Carotid IMT; FMD; CAC | Completed |
| Rosuvastatin 10mg | NCT02234492 | >40yrs; On ART with 10-yr CVD risk 10-20% and LDL <155 | Open-label RCT | 82 | Coronary flow reserve; Aortic TBR | Recruiting |
| Rosuvastatin 20mg | NCT01813357 | >18yrs; On ART with 10-15% 10-yr CVD risk | Placebo RCT | 102 | Carotid IMT; FMD | Recruiting |
| Rosuvastatin | NCT01881971 | 18-80yrs; On ART with COPD | Placebo RCT | 30 | Carotid IMT; FMD | Ongoing; not recruiting |
| Atorvastatin 20/40mg | NCT00965185 | 18-60; on ART with coronary plaque and high aortic TBR | Placebo RCT | 40 | Coronary plaque volume and high risk features by CT; Aortic TBR | Completed |
| Pitavastatin 4mg | NCT02344290 | 40-75yrs; on ART with <7.5% 10-yr ASCVD risk | Placebo RCT | 6500 | MACE; Coronary plaque volume and high risk features | Recruiting |
| ASA 81mg vs. Atorvastatin 40mg | NCT02081638 | >18yrs; elite controller compared to persons with >4yrs of ART | RCT | 80 | Carotid MRI | Recruiting |
| ASA 325mg | NCT02401269 | 18-70yrs; on ART without diabetes or heart disease | Placebo RCT | 100 | RHI and FMD | Recruiting |
| ASA 100 or 300mg | NCT02155985 | >18yrs; on ART | Placebo RCT | 121 | FMD | Ongoing; not recruiting |
| Telmisartan 80mg | NCT01578772 | >50yrs; on ART with one or more risk factors for CVD | Placebo RCT | 17 | FMD | Completed; not published |
| Losartan 100mg +/− switch to RAL | NCT01529749 | >18yrs; on ART as tenofovir DF, emtricitabine, and efavirenz | Placebo RCT; 2×2 factorial | 48 | Carotid IMT | Recruiting |
| Metformin 1000mg | NCT02383563 | >45yrs; on ART | Open label RCT | 12 | Total coronary plaques by CT | Recruiting |
| Lovaza (OM-3 FA) 2gm | NCT01001767 | 18-70yrs; on ART | Placebo RCT | 35 | FMD | Completed[71] |
CVD, cardiovascular disease; yrs, years; ART, antiretroviral therapy; RCT, randomized controlled trial; FMD, flow-mediated dilation of the brachial artery; IL, interleukin; Ab, antibody; VTI, velocity time integral; TBR, target to background ratio; LDL, low-density lipoprotein; hsCRP, high-sensitivity C-reactive protein; IMT, intima-media thickness; CAC, coronary artery calcium; COPD, chronic obstructive pulmonary disease; ASCVD, atherosclerotic cardiovascular disease; MACE, major adverse cardiovascular events; ASA, aspirin; MRI, magnetic resonance imaging; RHI, reactive hyperemic index; RAL, raltegravir; DF, disoproxil fumarate; OM-3 FA, omega-3 fatty acids.