Condition category
Haematological Disorders
Date applied
23/05/2008
Date assigned
19/06/2008
Last edited
18/08/2010
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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 measures

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

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

http://web.unina2.it

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

Results - basic reporting

Publication summary

2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20598989

Publication citations

  1. 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.

Additional files

Editorial Notes