Clinical trial NCT06286059: Efficacy of Phentolamine in Prevention of Contrast-Associated Acute Kidney Injury After Complex PCI
Official title: Protective Efficacy of Phentolamine in Patients at High Risk of Contrast-Associated Acute Kidney Injury After Complex Percutaneous Coronary Intervention
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: CA-AKI - Contrast-Associated Acute Kidney Injury
Coronary Artery Disease
Acute Coronary Syndrome
Adrenergic Receptor Antagonist Adverse Reaction
Lead sponsor: Helwan University
Sponsor class: OTHER
First posted: 2024-02-29
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised controlled clinical trial
Primary purpose: PREVENTION

Brief summary: To evaluate the efficacy and safety of phentolamine in prevention of CA-AKI following complex PCI in patients at high risk of CA-AKI.

Detailed description: Coronary angiography is accepted as the gold standard diagnostic procedure in the management of coronary artery disease (CAD). It involves the visualization of the coronary arteries using contrast dye and dynamic X-ray imaging and allows for the identification of suitable lesions for percutaneous coronary intervention (PCI). PCI has more importance when performed as an emergency procedure during acute coronary syndromes (ACS) providing immediate relief of symptoms, preventing myocardial damage and reducing mortality rates despite its potential complications. These complications varies in its incidence including arrhythmias, coronary dissection, bleeding at the access site, allergy to contrast agent and kidney injury with varying risk on patient condition.

Contrast-associate acute kidney injury (CA-AKI), formerly termed contrast-induced nephropathy (CIN), is a significant complication of PCI and the third most common cause of renal failure in hospitalized patients. It is defined as a rise in creatinine of ≥ 50% of baseline or 0.3 mg/dL from the pre-contrast value within 48-72 hours of intravascular administration of a contrast medium, which is usually reversible acute kidney injury. The development of CA-AKI despite successful percutaneous coronary procedures is associated with prolonged hospitalization, an increase in health expenditure, and increased short and long-term mortality for most patients. Therefore, early risk prediction and management is crucial.

Over the past few decades, a number of risk scores have been introduced to predict contrast-associated acute kidney injury after PCI. The most commonly used is Mehran score that was introduced in 2004 for its simplicity and availability but it excluded patients with acute myocardial infarction. However, it recently updated with larger population and more emphasis on patient's ACS presentation and procedural features and reintroduced in 2021 as Mehran 2 CA-AKI Risk Score.

Exact pathophysiological mechanism of CA-AKI is not known and includes complex cascades of events. The most important elements of pathophysiological mechanism of CA-AKI seem to be the medullary hypoxia due to contrast-induced medullary vasoconstriction and direct renal tubular cytotoxicity, in addition to oxidative stress and the increase in blood and renal tubular viscosity which are complementary events that further exacerbates CA-AKI.

Several clinical interventions aimed to reduce the incidence of CA-AKI targeting various aspects of the pathophysiology including volume expansion with intravenous fluid, administration of N-acetylcysteine, sodium bicarbonate, vitamin E, statins and vasodilator agents with different protective efficacy but only few of them had been approved for clinical practice.

Vasodilators agents like nicorandil showed a statistically significant lower odds of developing CA-AKI with periprocedural hydration and the vasodilator agent nicorandil versus periprocedural hydration only (OR: 0.173). Also, a recent clinical trial has demonstrated encouraging results regarding the renoprotective effects of phentolamine in chronic coronary syndrome following PCI with odds ratio 0.04 of CA-AKI in phentolamine group in comparison to control group.

Phentolamine, a non-selective alpha-adrenergic antagonist, is primarily used for the treatment of conditions involving excessive sympathetic activity. While it is not a commonly used medication in the management of CAD, it used in various cardiovascular urgent conditions as in hypertensive crisis and in the treatment of cocaine-induced ACS which counteract the excessive sympathetic stimulation and reduce peripheral vascular resistance in conjunction with other treatments to alleviate symptoms and improve hemodynamics with less incidence of tachycardia associated with other vasodilators e.g. nitroglycerin.

This clinical trial will investigate the potential of phentolamine as a renoprotective agent following complex PCI by evaluating the impact of phentolamine on renal outcomes and its safety which may significantly impact clinical practice by guiding the use of phentolamine as an adjuvant therapy, ultimately improving patient outcomes and reducing the burden of CA-AKI in high-risk population.

Eligibility criteria: Inclusion Criteria:

* Patients admitted to CCU with CAD.
* Patients underwent successful complex PCI defined as multivessel disease, more than two lesions, high coronary lesion complexity, chronic total occlusion, lesion length \>30 mm, or bifurcation.
* Patients at high or very high risk for CA-AKI based on Mehran-2 CA-AKI Risk Score (Model 2).

Exclusion Criteria:

* Patients with end stage renal disease on regular dialysis.
* Patients with failed PCI revascularization.
* Patients presented with STEMI and underwent primary PCI.
* Patients presented with high risk NSTEMI defined as elevated cardiac enzymes with chest pain refractory to medications and/or dynamic ST changes.
* Patients presented with cardiogenic shock.
* Patients presented with any degree of heart block.
* Patients with of history of asthma or hypersensitive for phentolamine.
* Patients on α-blockers, barbiturates or antipsychotic treatment.
* Patients intolerant to phentolamin with significant hemodynamic changes defined as \>20% drop of systolic blood pressure (SBP) or \>20% increase of heart rate (HR) after loading dose of phentolamine.

Primary outcomes:
measure: Rate of CA-AKI
timeFrame: 3 days post-PCI
Secondary outcomes:
measure: Peak of serum creatinine elevation
timeFrame: 7 days
measure: Duration of CA-AKI
timeFrame: 14 days
measure: Change in HR
timeFrame: 12 hours post-PCI
measure: Change in SBP
timeFrame: 12 hours post-PCI
measure: Change in DBP
timeFrame: 12 hours post-PCI
measure: Urine output
timeFrame: 12 hours post-PCI
measure: Rate of RRT
timeFrame: 7 days
measure: Rate of MACE
timeFrame: 30 days post-PCI
measure: Rate of rehospitalization
timeFrame: 30 days post-PCI
measure: Duration of hospitalization
timeFrame: 14 days
Other outcomes:
Locations:
city: Badr
country: Egypt
facility: Badr university hospital
state: Cairo
Study officials:
affiliation: Helwan University
name: Yasser Sadek, Professor
role: STUDY_CHAIR
affiliation: Helwan University
name: Arafa Gomaa, MD
role: STUDY_DIRECTOR
References:
citation: Hamila MA, El Ghawaby H, Zaki M, Soliman M, Gabr K. Association of periprocedural phentolamine infusion with favorable outcome in patients with chronic kidney disease and chronic coronary syndrome undergoing coronary catheterization: a prospective randomized controlled pilot study. BMC Nephrol. 2022 Dec 31;23(1):416. doi: 10.1186/s12882-022-03050-9.
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citation: Ozkok S, Ozkok A. Contrast-induced acute kidney injury: A review of practical points. World J Nephrol. 2017 May 6;6(3):86-99. doi: 10.5527/wjn.v6.i3.86.
citation: Walker H, Guthrie GD, Lambourg E, Traill P, Zealley I, Plumb A, Bell S. Systematic review and meta-analysis of prophylaxis use with intravenous contrast exposure to prevent contrast-induced nephropathy. Eur J Radiol. 2022 Aug;153:110368. doi: 10.1016/j.ejrad.2022.110368. Epub 2022 May 23.