Lowering the intensity of anticoagulation is safe and effective for patients with mechanical cardiac valve prosthesis

ISRCTN	ISRCTN34082835
DOI	https://doi.org/10.1186/ISRCTN34082835
Protocol serial number	N/A
Sponsor	Second University of Naples (Seconda Università degli studi di Napoli) (Italy)
Funder	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)

Submission date: 23/05/2008
Registration date: 19/06/2008
Last edited: 14/10/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Haematological Disorders

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Michele Torella
Scientific

Department of Cardio-Thoracic and Respiratory Sciences
Second University of Naples
Monaldi Hospital
Via Leonardo Bianchi, 41
Naples
80060
Italy

Phone	+39 (0)81 706 25 20
Email	michele.torella@unina2.it

Study information

Primary study design	Interventional
Study design	Single-centre, randomised controlled trial
Secondary study design	Randomised controlled trial
Scientific title	LOWering the INtensity of oral anticoaGulant Therapy in patients with mechanical aortic valve replacement: the LOWING-IT Trial
Study acronym	LOWING-IT
Study objectives	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(s)	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)
Health condition(s) or problem(s) studied	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
Primary outcome measure(s)	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.
Key secondary outcome measure(s)	No secondary outcome measures
Completion date	01/01/2005

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Not Specified
Target sample size at registration	420
Total final enrolment	292
Key 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
Key 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)
Date of first enrolment	01/01/2001
Date of final enrolment	01/01/2005

Locations

Countries of recruitment

Italy

Study participating centre

Department of Cardio-Thoracic and Respiratory Sciences

Naples
80060
Italy

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/07/2010		Yes	No
Results article	results	30/05/2018	14/10/2019	Yes	No

Editorial Notes

14/10/2019: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.