E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
right ventricular hypertrophy associated with COPD or Interstitial Lung Disease and pulmonary hypertension |
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E.1.1.1 | Medical condition in easily understood language |
COPD or Interstitial Lung Disease with enlarged right side of heart |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010952 |
E.1.2 | Term | COPD |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10022611 |
E.1.2 | Term | Interstitial lung disease |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10037400 |
E.1.2 | Term | Pulmonary hypertension |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10050326 |
E.1.2 | Term | Right ventricular hypertrophy |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective will be to see if Allopurinol can improve right ventricular hypertrophy in patients with pulmonary hypertension associated with COPD or interstitial lung disease(ILD). This will be done by measuring the size of the right side of the heart muscle with an MRI scan before and after one years of treatment with allopurinol or placebo. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to assess the effect of allopurinol on other functions of the heart, such as its pumping ability and the size of the left side of the heart This will be measured by scanning the heart using ultrasound and MRI scans, in patients with COPD or ILD and pulmonary hypertension. We will also assess the effect of allopurinol exercise capacity pre and post six minute walk test and how well the participants lungs are functioning with respect to how much oxygen is available in their blood and how well their lungs are working doing breathing tests. We will also assess if allopurinol improves quality of life in these participants. We will also assess the safety of allopurinol in COPD or ILD and its effects on inflammatory and other blood markers in COPD or ILD.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•participant is willing and able to give informed consent are aged 18 years or over • previously diagnosed with COPD or ILD • screening echocardiography based diagnosis of PH and/or RVH (RVSP>25mmHg, and/or PAT <110ms-2 and/or RVM >5.5mm) stable lung disease medication for at least two weeks prior to consent - women of child bearing potential must agree to shceduled pregnancy testing prior to and during study treatment period and to use an appropraite method of contraception if sexually active
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E.4 | Principal exclusion criteria |
- patients who are uinable to give informed consent • documented intolerance or allergy to allopurinol - objection to taking capsules made from animal sourced gelatine • left Ventricular Ejection Fraction <45% on echocardiography screening • severe aortic stenosis on echocardiography screening • already had gout or currently taking allopurinol • severe hepatic disease • renal disease; CKD class 3B or greater • taking prohibited medication:azathioprine, 6 mercaptopurine, or theophylline • malignancy (receiving active treatment) or other life threatening diseases • pregnant or lactating • any contraindication to MRI (claustrophobia, metal implants) • patients who have participated in any other clinical trial of an investigational medicinal product within the previous 30 days will be excluded • women unwilling to agreet to use an appropriate method of contraception during the study treatment period if sexually active • any other considered by a study physician to be inappropriate for inclusion
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome is to determine if allopurinol induces a change in Right Ventricular Mass Index in patients with COPD or ILD associated Pulmonary Hypertension when compared to placebo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary outcomes are: • To determine if there is a change in RVEDV, RVESV, RVEF, LV Mass, LVESV, LVEDV, LVEF or pulmonary compliance with allopurinol in COPD/ILD patients compared with placebo. • To determine if there is a difference in pulmonary artery pressure, RVSP, or PAT with allopurinol compared with placebo as measured by both echocardiography and/or MRI. • To determine if allopurinol improves oxygen saturation as measured pre and post 6MWT in COPD/ILD compared with placebo. • To determine if allopurinol improves exercise capacity as measured by 6MWT in COPD/ILD compared with placebo. • To determine if there is an improvement in quality of life measures in COPD/ILD with allopurinol compared to placebo. • To determine if there are changes in inflammatory and other blood markers, in COPD/ILD with allopurinol compared with placebo.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
12 MONTHS FOR ALL OF ABOVE |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 30 |