Condition category
Circulatory System
Date applied
11/02/2015
Date assigned
17/02/2015
Last edited
17/02/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
People with lung disease are at an increased risk of heart complications. One of the biggest problems is that the muscle wall of the heart thickens. The medical term for this is right ventricular hypertrophy (RVH). RVH makes the heart work less well and patients with RVH are at a greater risk of heart complications than those without it. The pressure in the blood vessel between this heart chamber and the lungs can also increase. This is called pulmonary artery hypertension (PAH). This can leave patients more breathless as the blood is not picking up oxygen well from the lungs. It has previously been shown that a drug called allopurinol, which is usually used to treat gout, had the noteworthy side effect of being able to reduce thickening of the left side of the heart wall in patients who had kidney disease or diabetes. The aim now is to see if patients with lung disease and raised pressure in their right side of the heart may also benefit from treatment with allopurinol. If RVH can be reduced using allopurinol, this might be a new way to reduce cardiac risk in these patients and possibly improve their ability to exercise and reduce symptoms.

Who can participate?
Adult patients who have lung disease with raised PAH.

What does the study involve?
Participants are randomly allocated into one of two groups. Those in group 1 are given allopurinol for a year. Those in group 2 are given a placebo for a year. All currently prescribed medication for each participants lung disease continue as normal throughout the study. All participants have a magnetic resonance imaging (MRI) scan of their heart before the study starts and after their treatment ends so that we can compare if there is a difference between normal treatment and addition of allopurinol.

What are the possible benefits and risks of participating?
Participants may find that taking part in this study improves their exercise tolerance and their PAH symptoms. Adverse side effects may include a skin rash, nausea, vomiting, diarrhoea, dizziness, and an acute attack of gout.

Where is the study run from?
NHS Tayside - University of Dundee (UK)

When is the study starting and how long is it expected to run for?
February 2015 to July 2017

Who is funding the study?
British Heart Foundation (UK)

Who is the main contact?
Dr Patrick Liu Shiu Cheong
p.s.k.liushiucheong@dundee.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Dr Patrick Liu Shiu Cheong

ORCID ID

http://orcid.org/0000-0002-3005-7580

Contact details

Mailbox 2
Division of Cardiovascular & Diabetes Medicine
Ninewells Hospital & Medical School
Dundee
DD1 9SY
United Kingdom
+44 1382 383013
p.s.k.liushiucheong@dundee.ac.uk

Additional identifiers

EudraCT number

2014-002305-38

ClinicalTrials.gov number

Protocol/serial number

2013CV11

Study information

Scientific title

Does allopurinol reduce right ventricular mass in lung disease associated pulmonary hypertension?

Acronym

ALPHA

Study hypothesis

The aim of this study is to determine whether allopurinol reduces right ventricular mass in lung disease associated pulmonary hypertension

Ethics approval

East of Scotland Research Ethics Service, 11/08/2014, ref. 14/ES/1035

Study design

Randomised double-blinded placebo-controlled single-centre study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a patient information sheet: p.s.k.liushiucheong@dundee.ac.uk

Condition

Pulmonary hypertension and chronic obstructive pulmonary disease / interstitial lung disease

Intervention

1. Treatment arm: Allopurinol 100mg once daily for 2 weeks, then increased to 300mg once daily for 4 weeks and increased to 300mg twice daily for further 46 weeks.
2. Placebo arm: Microcrystalline cellulose one tablet daily for one month then twice daily for eleven months.

Intervention type

Drug

Phase

Not Applicable

Drug names

Allopurinol

Primary outcome measures

The change in right ventricular (RV) mass index with allopurinol versus placebo after 12 months of treatment. Cardiac Magnetic Resonance Imaging scan will be done at the baseline and at the end of the 12 month study period on a 3T Magnetom scanners (Siemens, Erlangen, Germany) using dedicated phase array cardiac and phosphorus spectroscopy coils. Analysis will be performed offline (Argus Software, Siemens) by a single blinded observer for the assessment of ventricular volumes. This single observer will analyse all the scans. The reproducibility of the RV mass assessment using MRI will be derived for this observer. The change RV mass index in participants treated with allopurinol will be compared with placebo.

Secondary outcome measures

1. Measure a change in RV end diastolic volume, RV ejection fraction, left ventricular (LV) mass, LV end systolic volume, LV end diastolic volume or LV ejection fraction and pulmonary compliance. Timescale: 12 months. Cardiac Magnetic Resonance Imaging scan will be done at the baseline and at the end of the 12 month study period on a 3T Magnetom scanners (Siemens, Erlangen, Germany) using dedicated phase array cardiac and phosphorus spectroscopy coils. Analysis will be performed offline (Argus Software, Siemens) by a single blinded observer for the assessment of ventricular volumes. This single observer will analyse all the scans.
2. Determine if there is a difference in pulmonary artery pressure, RVSP, or PAT with allopurinol compared with placebo. Timescale: 12 months. Cardiac Magnetic Resonance Imaging scan will be done at the baseline and at the end of the 12 month study period on a 3T Magnetom scanners (Siemens, Erlangen, Germany) using dedicated phase array cardiac and phosphorus spectroscopy coils. Analysis will be performed offline (Argus Software, Siemens) by a single blinded observer for the assessment of ventricular volumes. This single observer will analyse all the scans. Echocardiogram will be done at baseline and at the end of the 12 month study period.
3. Change in oxygen saturation as measured pre and post six minute walk test (6MWT) with allopurinol versus placebo. Timescale: 12 months. On each occasion that the 6MWT is carried out, it will be done twice with a break of at least 1 hour in between and on an even floor with vocal support from the investigator which is in full accord with American Thoracic Society guidelines. The distance achieved on the second walk will be taken as the main result as recommended for lung studies. Patients on long term oxygen therapy (LTOT) will undergo 6MWT off oxygen.
4. Change in exercise capacity as measured by 6MWT with allopurinol versus placebo. Timescale: 12 months. On each occasion that the 6MWT is carried out, it will be done twice with a break of at least 1 hour in between and on an even floor with vocal support from the investigator which is in full accord with American Thoracic Society guidelines. The distance achieved on the second walk will be taken as the main result as recommended for lung studies. Patients on long term oxygen therapy (LTOT) will undergo 6MWT off oxygen.
5. Change in quality of life (QOL) measures with allopurinol compared to placebo
Timescale: 12 months. QOL measures will be carried out at baseline and 12 month visits. St George's Respiratory Questionnaire (SGRQ) will be used as disease specific QOL measure in patients with COPD. King's Brief Interstitial Lung Disease (K-BILD) QOL questionnaire will be used as a measure of health status for patients with ILD. SF-36 questionnaire will be as a general QOL measure and BDI/TDI questionnaire will be used for assessment of functional impairment.
6. Change in inflammatory and other blood markers with allopurinol compared with placebo. Timescale: 12 months. Research blood tests will be taken at baseline and at the final visit at month 12. They will include BNP, inflammatory markers and other markers of interest such as oxidative stress. Additional blood markers may be tested on the samples at a later date.

Overall trial start date

01/02/2015

Overall trial end date

31/07/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged 18 years or over
2. Previously diagnosed with COPD or ILD
3. Screening echocardiography based diagnosis of PH as indicated by RVSP>25mmHg, and/or PAT <110ms-2 and/or RVM >5.5mm
4. Stable lung disease medication for at least two weeks prior to consent
5. Women of child bearing potential must agree to scheduled pregnancy testing prior to and during study treatment period and to use an appropriate method of contraception if sexually active

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

72

Participant exclusion criteria

1. Documented allergy or intolerance to allopurinol
2. Objection to taking capsules made from animal sourced gelatine
3. Left Ventricular Ejection Fraction <45% on echocardiography screening
4. Severe aortic stenosis on echocardiography (screening)
5. Already had gout or currently taking allopurinol
6. Severe hepatic disease
7. Renal disease; CKD class 3B or greater
8. Taking prohibited medication; azathioprine, 6 mercaptopurine, or theophylline
9. Malignancy (receiving active treatment) or other life threatening diseases
10. Pregnant or lactating
11. Women unwilling to agree to use an appropriate method of contraception during the
study treatment period if sexually active
12. Any contraindication to MRI (claustrophobia, metal implants)
13. Patients who have participated in any other clinical trial of an investigational medicinal product within the previous 30 days will be excluded
14. Any other considered by a study physician to be inappropriate for inclusion

Recruitment start date

01/03/2015

Recruitment end date

31/07/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

NHS Tayside - University of Dundee
Division of Cardiovascular & Diabetes Medicine Ninewells Hospital & Medical School
Dundee
DD1 9SY
United Kingdom

Sponsor information

Organisation

NHS Tayside - University of Dundee

Sponsor details

c/o Catrina Forde
Tayside Medical Sciences Manager
Ninewells Hospital & Medical School
TASC Research & Development Office
Residency Block
Level 3
George Pirrie Way
Dundee
DD1 9SY
United Kingdom

Sponsor type

Hospital/treatment centre

Website

http://www.dundee.ac.uk

Funders

Funder type

Charity

Funder name

British Heart Foundation

Alternative name(s)

BHF

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Intention to publish date

Participant level data

Other

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes