Effect of LOW-molecular-weight Heparin in Reducing Radial Artery Occlusion Rate After Transradial Coronary Catheterization (LOW-RAO)

A Prospective, Randomized, Open-label Study to Evaluate the Effect of LOW-molecular-weight Heparin in Reducing Radial Artery Occlusion Rate After Transradial Coronary Catheterization Procedures

The purpose of the LOW-RAO study is to determine the most effective treatment for radial artery occlusion (RAO) after transradial coronary catheterization (both angiography and PCI). This is a prospective, single-center, randomized controlled, open-label study that will randomize patients with RAO into two groups, one receiving anticoagulation with low-molecular-weight-heparin (LMWH) and the other receiving no anticoagulation. RAO will be detected by radial artery ultrasound up to 24 hours after the procedure.

Study objectives:

1. Primary objective:

   a. To evaluate the effect of treatment with LMWH, in patients (both symptomatic and asymptomatic) with RAO after a coronary catheterization procedure (both angiography and percutaneous coronary intervention-PCI), in improving patency rates of the radial artery at 1 month after the procedure, compared with no-LMWH treatment.

2. Secondary objectives:

   1. To compare RAO as defined by different methods (pulse palpation, modified Allen's test, reverse Barbeau test, radial artery ultrasound).
   2. To compare local access site and systemic complications (bleeding events, pseudoaneurysm, arteriovenous fistula) at 1 month after the procedure in the LMWH and no-LMWH groups.
   3. To evaluate RAO incidence in coronary angiography and PCI groups.
   4. To determine risk factors for RAO in coronary catheterization procedures.

Study Overview

• Status: Completed
• Conditions: Arterial Occlusion
• Intervention / Treatment: Drug: low molecular weight heparin

Detailed Description

The use of the radial artery as an access site for coronary catheterization procedures, is constantly increasing because of lower rate of access site complications, shorter hospital stay, improved patient comfort and safe hemostasis. Radial artery occlusion remains a concern after transradial procedures, with a varied incidence, ranging from 5 to 38% as reported in the literature and probably reflecting different evaluation methods (pulse palpation versus ultrasound).

Although perceived as usually asymptomatic, registry data report that RAO may be symptomatic in up to 58.8% of patients, presenting as pain in the forearm, numbness/ paresthesia, paresis or acute ischemia. Moreover RAO excludes the affected vessel from future catheterization procedures, hemodialysis shunts, invasive hemodynamic monitoring, coronary arterial bypass grafting.

Spontaneous recanalization of the vessel after RAO ranges from 5.4 to 47% at 1-month follow up. Today there is no evidence-based therapy, in the frame of a randomized control study, for the treatment of RAO. Heparinization has been found to be effective in reducing the occurrence of radial artery occlusion and short-term treatment with low-molecular-weight heparin (LMWH) in symptomatic patients increases the patency rate of the radial artery after coronary catheterization procedures, without increasing bleeding complications, as depicted by registry data.

This is a prospective, randomized, multicenter study that will enroll, after informed written consent, all consecutive patients presenting with RAO, after a coronary catheterization procedure (both angiography and PCI) through the transradial access and having successfully received at least one radial artery sheath of any size at the end of the procedure.

RAO will be diagnosed by radial artery ultrasound (2D, Doppler, colour) performed in all patients after sheath removal and successful local hemostasis and before hospital discharge. Clinical evaluation of radial artery patency with pulse palpation, modified Allen's test and reverse Barbeau test will be also applied in all patients.

Patients diagnosed with RAO will be randomized 1:1 into two groups:

1. Treatment group, that will receive LMWH (tinzaparin) for 1 month (at body-weight-adjusted therapeutic dose).
2. Control group, that will not receive additional LMWH. All asymptomatic patients, with patent radial artery at initial work-up, will be provided with the opportunity to return to the center for further evaluation, clinically and by ultrasound, if they become symptomatic at any time after hospital discharge, in order to diagnose late RAO.

They will also be provided with the opportunity to be randomized to LMWH or not in case RAO is diagnosed and after informed written consent.

Patients already on anticoagulation for any other reason will neither be excluded nor randomized, but will be followed-up as the randomized ones, in order to collect data from this patient population.

All patients with RAO will be re-evaluated by radial artery ultrasound at 1-, 2- 4- weeks to determine radial artery patency and record any bleeding complications according to the EASY (Early Discharge After Transradial Stenting of Coronary Arteries) Hematoma Classification and the BARC (Bleeding Academic Research Consortium) bleeding definition.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Greece
  • Thessaloníki, Greece, 54636
    • 1st Cardiology Department, University General Hospital AHEPA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients (both male and female) undergoing a coronary catheterization procedure (both angiography and PCI) through the transradial access and having successfully received at least one radial artery sheath of any size at the end of the procedure.
• Radial artery occlusion confirmed by ultrasound (2D, Doppler, colour)

Exclusion Criteria:

• Age < 18 years
• Unable to provide informed written consent
• Any contraindication to receive LMWH.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control group; No intervention
Experimental: Tinzaparin group; LMWH (tinzaparin) for 1 month (at body-weight-adjusted therapeutic dose)	Drug: low molecular weight heparin; LMWH (tinzaparin) at body-weight-adjusted therapeutic dose (175 anti-Xa IU/kg subcutaneously once daily)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radial artery patency	To evaluate the effect of treatment with LMWH, in patients (both symptomatic and asymptomatic) with RAO after a coronary catheterization procedure (both angiography and percutaneous coronary intervention-PCI), in improving patency rates of the radial artery at 1 month after the procedure, compared with no-LMWH treatment.	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bleeding events	To compare bleeding events (based on the BARC bleeding definition) at 1 month after the procedure between the LMWH and no-LMWH groups.	1 month
RAO incidence	To evaluate RAO incidence in coronary angiography and PCI groups.	24 hours
Pain at the forearm	To compare incidence of pain at any region of the forearm at 1 month after the procedure between the LMWH and no-LMWH groups.	1 month

Collaborators and Investigators

• Sponsor: AHEPA University Hospital
• Investigators: Principal Investigator: Antonios Ziakas, MD, PhD, 1st Cardiology Department, University General Hospital AHEPA, Thessaloniki; Principal Investigator: Matthaios V. Didagelos, MD, 1st Cardiology Department, University General Hospital AHEPA, Thessaloniki

Publications and helpful links

General Publications

• Didagelos M, Pagiantza A, Zegkos T, Papanastasiou C, Zarra K, Angelopoulos V, Kouparanis A, Peteinidou E, Sianos G, Karvounis H, Ziakas A. Low-molecular-weight heparin in radial artery occlusion treatment: the LOW-RAO randomized study. Future Cardiol. 2022 Feb;18(2):91-100. doi: 10.2217/fca-2021-0067. Epub 2021 Aug 16.

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2017
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: November 25, 2019
• First Submitted That Met QC Criteria: December 10, 2019
• First Posted (Actual): December 12, 2019

Study Record Updates

• Last Update Posted (Actual): July 30, 2021
• Last Update Submitted That Met QC Criteria: July 28, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: coronary artery disease; anticoagulation; radial artery occlusion; coronary catheterization
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin
• Other Study ID Numbers: 79/09-02-2018; 427/01-06-2018 (Other Identifier: Bioethics committee, Medical School, AUTH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No