Contact information
Type
Scientific
Primary contact
Dr Michele Torella
ORCID ID
Contact details
Department of Cardio-Thoracic and Respiratory Sciences
Second University of Naples
Monaldi Hospital
Via Leonardo Bianchi
41
Naples
80060
Italy
+39 (0)81 706 25 20
michele.torella@unina2.it
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
LOWering the INtensity of oral anticoaGulant Therapy in patients with mechanical aortic valve replacement: the LOWING-IT Trial
Acronym
LOWING-IT
Study hypothesis
The present randomised study tested the hypothesis that a low intensity level oral anticoagulant regime with an international normalised ratio (INR) range between 1.5 to 2.5 is as effective and safe as a higher level of anticoagulant therapy with a recommended INR range of 2.0 to 3.0, in patients with a single aortic mechanical prosthetic valve replacement. In particular, the hypothesised outcome from using a 1.5 to 2.5 INR intensity level (as opposed to the currently recommended INR of 2.0 to 3.0) was a reduction in the incidence of haemorrhagic episodes without affecting the risk of thromboembolic events.
Ethics approval
The Ethics Committee of the Postgraduate School of Pathophysiology of the Cardiorespiratory System and Associated Biotechnologies, Second University of Naples granted the initial ethics approval for this trial in December 2000. However, our internal regulations have changed to be in line with the international guidelines since the time of initial approval, and this trial was re-submitted and then re-approved by the Ethics Committee of the Monaldi Hospital, Naples on 23/06/2008 (ref: #15)
Study design
Single-centre, randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Anticoagulant therapy
Intervention
The participants were enrolled from January 2001 to January 2005. They were allocated to the following two arms:
Intervention arm: Low intensity oral anticoagulant regime with an INR range between 1.5 to 2.5
Control arm: Higher level of anticoagulant therapy with a recommended INR range of 2.0 to 3.0
The follow-up of the interventions was 4.3 ± 0.9 years.
Intervention type
Other
Phase
Not Specified
Drug names
Primary outcome measure
Thromboembolic and haemorrhagic events, followed-up for 4.3 ± 0.9 years:
1. Cerebral infarction
2. Coronary and/or peripheral embolism
3. Valve thrombosis
4. Intracranial and spinal bleeding
5. Major extra-cranial bleeding
6. Endocarditis
7. Withdrawal from the oral anticoagulant therapy
8. Death
Cerebral thromboembolic events included the onset of a transient or definitive symptomatic neurological stroke and/or evidence of an ischaemic vascular brain sequela on a computerised tomography (CT) brain scan. Coronary or peripheral embolic events were documented by echo Doppler, angiography, or surgery. Prosthesis thrombosis was defined as impairment of the valve by the deposition of thrombus, demonstrated by echo Doppler or surgery. Haemorrhagic events were considered to be major when blood transfusion, hospitalisation, or a surgical procedure was required. Other haemorrhages were considered to be non-major but were recorded.
Secondary outcome measures
No secondary outcome measures
Overall trial start date
01/01/2001
Overall trial end date
01/01/2005
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Both male and female patients, aged 20 - 60 years
2. Those presenting for a first single-valve replacement with a bileaflet mechanical prosthesis in the aortic position
3. Those with a low thrombo-embolic risk
4. Valve prosthesis dimension greater than 21 mm
5. Normal ejection fraction (EF)
6. Left atrium diameter less than 47 mm
7. Normal sinus rhythm
Participant type
Patient
Age group
Adult
Gender
Not Specified
Target number of participants
420
Participant exclusion criteria
1. Contraindication to anticoagulant treatment (including pregnant women)
2. Valvular prosthesis on another orifice
3. Dialysed renal failure
4. Hepatic insufficiency
5. Patient or general practitioner refusal to participate in the study
6. Patients with a high risk of thromboembolic events (i.e. atrial fibrillation, history of cardiac thromboembolism, left atrial diameter greater than 47 mm on a time-motion echocardiogram, thrombosis or calcification of the left atrium) (exclusion for ethical reasons)
Recruitment start date
01/01/2001
Recruitment end date
01/01/2005
Locations
Countries of recruitment
Italy
Trial participating centre
Department of Cardio-Thoracic and Respiratory Sciences
Naples
80060
Italy
Sponsor information
Organisation
Second University of Naples (Seconda Università degli studi di Napoli) (Italy)
Sponsor details
Department of Cardio-Thoracic and Respiratory Sciences
Monaldi Hospital
Via Leonardo Bianchi
41
Naples
80060
Italy
+39 (0)81 7701593
Maurizio.COTRUFO@unina2.it
Sponsor type
University/education
Website
Funders
Funder type
University/education
Funder name
Funded by the PhD Programme in Cardiologic Sciences, Postgraduate School of Medical Surgical Pathophysiology of the Cardiorespiratory System and Associated Biotechnologies, Second University of Naples, Naples (Italy)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20598989
Publication citations
-
Results
Torella M, Torella D, Chiodini P, Franciulli M, Romano G, De Santo L, De Feo M, Amarelli C, Sasso FC, Salvatore T, Ellison GM, Indolfi C, Cotrufo M, Nappi G, LOWERing the INtensity of oral anticoaGulant Therapy in patients with bileaflet mechanical aortic valve replacement: results from the "LOWERING-IT" Trial., Am. Heart J., 2010, 160, 1, 171-178, doi: 10.1016/j.ahj.2010.05.005.