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
Secondary identifying numbers N/A
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

Study designSingle-centre, randomised controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Scientific titleLOWering the INtensity of oral anticoaGulant Therapy in patients with mechanical aortic valve replacement: the “LOWING-IT” Trial
Study acronymLOWING-IT
Study objectivesThe 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) studiedAnticoagulant therapy
InterventionThe 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 typeOther
Primary outcome measureThromboembolic 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 measuresNo secondary outcome measures
Overall study start date01/01/2001
Completion date01/01/2005

Eligibility

Participant type(s)Patient
Age groupAdult
SexNot Specified
Target number of participants420
Total final enrolment292
Key inclusion criteria1. 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 criteria1. 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 enrolment01/01/2001
Date of final enrolment01/01/2005

Locations

Countries of recruitment

  • Italy

Study participating centre

Department of Cardio-Thoracic and Respiratory Sciences
Naples
80060
Italy

Sponsor information

Second University of Naples (Seconda Università degli studi di Napoli) (Italy)
University/education

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

Phone +39 (0)81 7701593
Email Maurizio.COTRUFO@unina2.it
Website http://web.unina2.it
ROR logo "ROR" https://ror.org/05290cv24

Funders

Funder type

University/education

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)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot 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.