Upfront Premedication For Reduction of Microvascular Obstruction and No-reflow in Treating ST-segment Elevation Myocardial Infarction

NCT05393557 | Not Yet Recruiting DMC

• 1 other identifier: 20220204MYFAHC
• Study Type: interventional
• Target: 626
• Locations: 0 countries
• Sites: N/A

Brief Summary

Angiographic no-reflow during primary PCI procedures occurs at relatively high rate (25%) and is associated with worsening of long term morbidity and mortality. The exact mechanism of no-reflow is not fully understood, yet it is believed to be multifactorial including microvascular plugging with activated platelets and thrombotic debris in addition to the microvascular dysfunction from the ischaemia-reperfusion injury. Despite a theoretical advantage of glycoprotein IIb/IIIa inhibitors (GPi) (like; Tirofiban) to suppress the intense platelets' activation/reaction; their use did not lead to a significant net benefit, because it was opposed by increased risk of bleeding. However, the bleeding that plagued GPi use was predominantly related to vascular access in the era femoral approach was the default. Moreover, there are some recent data suggesting that small intracoronary bolus of GPi was non-inferior to intravenous bolus-infusion dose with less bleeding events. This study plans to assess upfront premedication with small doses of GPi + Nitroglycerin ± Verapamil, with staged restoration of flow (repeated balloon inflation) to reduce angiographic no-reflow and CMR assessed microvascular occlusion (MVO).

Conditions

STEMI; Large Thrombus Burden; No-Reflow Phenomenon

Keywords

No reflow; STEMI; Glycoprotein inhibitor; repeated intermittent balloon inflation; reperfusion injury

Outcome Measures

Primary Outcomes (2)

• Efficacy endpoint: Reducing rates of suboptimal PCI results

  Sub-optimal PCI results defined as any of: 1. Final TIMI flow \< 3, TIMI myocardial blush grade \< 3, corrected TIMI flow count (cTFC) \< 20, 2. Occurrence of TIMI flow \< 3 during stenting/post dilation, (no reflow) 3. ST elevation resolution \< 50% in the index lead assessed within 30m from the procedural end.

  One day (assessed by the end of the procedure)

• Safety endpoint: Occurrence of intrahospital BARC types 3 or 5 bleedings

  Occurrence of intrahospital BARC types 3 or 5 bleedings

  30 days

Secondary Outcomes (8)

• Occurrence of slow flow/no reflow after stent deployment or stent optimization (TIMI flow < 3)

  one day (assessed by the end of the procedure)

• Final TIMI flow

  one day (assessed by the end of the procedure)

• Final TIMI myocardial blush grade

  One day (assessed by the end of the procedure)

• NT-BNP at 90 days

  90 days

• LVEF at 90 days

  90 days

Study Arms (2)

Upfront

ACTIVE COMPARATOR

Immediately after restoration of distal flow, they will receive: i. Small dose Tirofiban (intra-coronary bolus of 25µg/Kg),\[22\] ii. Nitroglycerin 100-200 µg,\[12\] iii. Verapamil 100-200 µg (excluding patients with 2nd or 3rd degree AV block, bradycardia HR \< 60, or systolic BP \<100 mmHg)\[5\] iv. Two cycles of balloon up-balloon down (15 seconds occlusion, 15 seconds open artery; repeated two times). v. The rest of the procedure will be completed as standard practice.

Other: Upfront preparation of microcirculation to minimize risks of no-reflow and reperfusion injury

Control

NO INTERVENTION

pPCI procedure will be performed as per standard practice.\[2\] Bail-out use of any pharmaceutical products will be allowed as per guidelines recommendations (such as: GPi in case of no-reflow or thrombotic complications).

Interventions

Upfront preparation of microcirculation to minimize risks of no-reflow and reperfusion injury OTHER

Tirofiban (intra-coronary bolus of 25µg/Kg) + Nitroglycerin (intracoronary 100-200 µg) + Verapamil (intracoronary 100-200 µg, yet excluding patients with 2nd or 3rd degree AV block, HR \< 60, or SBP \<100 mmHg) + 2 cycles of intermittent balloon inflation

Upfront

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• STEMI patients with time from symptom onset of \< 24 hours duration.
• Large thrombus burden confirmed after initial wiring.
• Radial vascular access.

You may not qualify if:

• STEMI patients receiving successful fibrinolytic therapy.
• TIMI flow ≥ 1 or TIMI thrombus grade ≤ 3 at initial wiring.
• Refusal to participate int the study, or unable to be consented (unconscious or comatose patients).
• Femoral access.
• Previous infarction in the same territory.
• Patients receiving PTCA only for acute reperfusion and planned for CABG.
• Patients with known intolerance or contraindications for CMR, such as claustrophobic or those with mechanical heart valve prothesis, or implantable non-conditional heart rhythm devices.

Sponsors & Collaborators

• Cairo University: lead
• Aswan Heart Centre: collaborator

MeSH Terms

Conditions

ST Elevation Myocardial Infarction; No-Reflow Phenomenon; Reperfusion Injury

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Postoperative Complications

Study Officials

• Ahmad Samir

  Aswan Heart Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ahmad Samir

CONTACT

1002647275; ahmad.samir@kasralainy.edu.eg

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: May 23, 2022
• First Posted: May 26, 2022
• Study Start: January 1, 2024
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: August 31, 2023

Record last verified: 2023-08