Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05251129 |
| Other study ID # |
2021-13700 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 2025 |
| Est. completion date |
June 2030 |
Study information
| Verified date |
December 2023 |
| Source |
Montefiore Medical Center |
| Contact |
Omar Saeed, MD, MS |
| Phone |
718-920-2626 |
| Email |
osaeed[@]montefiore.org |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The investigator's propose to conduct an open-label randomized controlled trial to determine
if higher intensity statin (HS) can reduce CAV in comparison to lower intensity statin (LS)
after HT. All consecutive patients that meet eligibility criteria will be approached for
participation. After heart transplantation, participants (n=70) will be randomized in a 1:1
manner to either HS (Atorvastatin 80 mg daily) or LS (Pravastatin 40 mg daily). Study
participation will be for 2 years from the time of randomization.
Description:
Outcomes after heart transplantation (HT) are limited by development of coronary allograft
vasculopathy (CAV). CAV comprises of macro- and microvascular coronary disease and is the
third leading cause of graft dysfunction and late mortality following HT. The pathophysiology
of CAV is multifactorial and major pathways that are implicated include inflammation and
dyslipidemia. These pathways are inhibited by statins which serve as the mainstay of CAV
prevention.
The International Society of Heart and Lung Transplantation (ISHLT) guidelines recommend
administration of low intensity statins (LS) due to a potential drug-drug interaction (DDI)
with calcineurin inhibition (CNI) therapy. This DDI is related to concurrent use of an older
generation CNI, cyclosporin A (CsA). CsA inhibits intestinal P-glycoprotein to reduce the
efflux of statin into the gastrointestinal tract, thereby increasing statin levels in the
blood and risk of myopathy. However, the current generation of CNI being utilized in most
patients, Tacrolimus, does not inhibit P glycoprotein and may not impact statin levels after
HT.
Despite use of LS, the residual risk of CAV development is elevated with nearly half of the
patients having angiographic detection 5 years after HT. However, angiography is limited by
its inability to detect microvascular disease and invasiveness. Early CAV is also detectable
by non-invasive imaging with cardiac positron emission tomography (cPET) through measurement
of myocardial flow reserve (MFR). MFR assesses total burden of macro- and microvascular
disease and is well correlated with invasive measures of CAV and prognosis.
The protective and inhibitory effects of statins are proportional to their intensity with
higher intensity statins (HS) leading to a greater reduction in low density lipoprotein (LDL)
and inflammatory markers such as C-reactive protein (CRP) in comparison to LS. Despite these
potentially beneficial effects of HS, LS remains the agent of choice for primary prevention
of CAV after HT in the absence of a randomized controlled trial (RCT).
The investigator's propose to conduct an open-label RCT to determine if HS can reduce CAV in
comparison to LS after HT. All consecutive HT candidates that meet eligibility criteria will
be approached for participation. After HT, participants (n=70) will be randomized in a 1:1
manner to either HS (Atorvastatin 80 mg daily) or LS (Pravastatin 40 mg daily). Study
participation will be for 2 years from the time of randomization. Study outcomes will be
compared by research staff blinded to statin group assignment.
