E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10005729 |
E.1.2 | Term | Blood pressure ambulatory |
E.1.2 | System Organ Class | 10022891 - Investigations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020775 |
E.1.2 | Term | Hypertension arterial |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10005756 |
E.1.2 | Term | Blood pressure systolic |
E.1.2 | System Organ Class | 10022891 - Investigations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020772 |
E.1.2 | Term | Hypertension |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10005735 |
E.1.2 | Term | Blood pressure diastolic |
E.1.2 | System Organ Class | 10022891 - Investigations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033762 |
E.1.2 | Term | Paracetamol |
E.1.2 | System Organ Class | 10022891 - Investigations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10005727 |
E.1.2 | Term | Blood pressure |
E.1.2 | System Organ Class | 10022891 - Investigations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10015488 |
E.1.2 | Term | Essential hypertension |
E.1.2 | System Organ Class | 10047065 - Vascular 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 |
To determine the effect of parcetamol on blood pressure in hypertensives adults taking or not taking antihypertensive medications. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
1. PATH-BP Urine Prostaglandin study
The pain relieving effect of paracetamol is thought to be due to the inhibition of the enzyme that controls prostaglandin synthesis. There is some evidence to show that paracetamol can inhibit prostaglandin production in the kidney and reduce urine sodium excretion. This is important because we suspect that through this mechanism of sodium retention, paracetamol may increase blood pressure. Prostaglandins from the kidney can be accurately measured in women from urine, but in men prostaglandins are excreted into urine from both the prostate gland and the kidney. So, for an accurate assessment of the effect of paracetamol on prostaglandin synthesis from the kidney, we will ask only women to participate in this sub-study.
Female participants will be asked to perform a 24-hour urine collection 4 times throughout the study, before and after each treatment period. This may be inconvenient and they must avoid sexual intercourse on the day before and the day of each collection. They will be given a thorough explanation of how to perform the collection, and they will be provided with a urine container.
This sub study will not require any additional study visits to the CRC. We will ask patients to drop off the urine collection on the same day they are returning the BP equipment to the CRC. These samples will be analysed at the Vascular Biology Laboratory, Queens Medical Research Institute, Edinburgh.
2. PATH-BP Biomarker Study
Paracetamol is very safe in therapeutic doses. However, in overdose, paracetamol can result in acute liver failure and even death. Diagnosis of liver injury following overdose is delayed because current blood tests are slow to detect damage. New blood markers of liver injury has been identified that are increased in concentration earlier in patients following a paracetamol overdose compared to current liver markers. Potentially, these markers may identify patients at risk of liver failure earlier and allow treatment to be initiated sooner.
There is evidence to suggest that taking paracetamol within the recommended daily amount may cause a very small increase in standard liver tests. Upon stopping paracetamol the liver tests return to normal. Therefore, the objective of this sub-study is to further explore our new markers and determine whether they change in concentration when no liver damage from paracetamol has occurred.
During the study, participants will be taking paracetamol 1g qid or placebo for 14 days. Participants will be attending the CRC on days 0, 4,7 and 14 for a BP check, renal function check, and paracetamol levels (to ensure compliance). If participants agree to participate in this sub-study, additional blood samples (10mls) will be taken for liver function tests and biomarker analysis.
In addition, a blood sample (5mls) will be taken on day 1 for DNA analysis. These samples will be stored in the -80 freezer in CRC until the study is complete. The samples will be analysed at Institute of Translational Medicine, University of Liverpool were they have pioneered the technique of liver biomarker analysis through previous collaborative work with Dr J Dear, University of Edinburgh.
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E.3 | Principal inclusion criteria |
Inclusion criteria: ≥18 years old, men or post-menopausal women. Half of the patients recruited will be women (to allow PG measurement). Treated hypertensive patients with an average daytime ABPM <150/95mmHg on stable doses of one or more antihypertensive medication (at least one of which should be; an ACEi, ARB or diuretic) for 3 months, or untreated hypertensive patients with an average daytime ABPM ≥135/85 but <150/95. |
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E.4 | Principal exclusion criteria |
Exclusion criteria: History of ischaemic heart disease, cardiac failure, cerebrovascular disease, liver impairment (ALT/AST>50IU/L) or stage 3-5 chronic kidney disease. Patients with a history of overdose or suicidal ideation. Patients weighing <55kgs. Patients with chronic pain requiring treatment, with a known allergy to paracetamol, or concomitant use of NSAIDs, oral anticoagulants or corticosteroids. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Difference in mean daytime systolic ambulatory BP between the paracetamol and placebo periods. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Daytime systolic ambulatory BP will be assessed at the start and end of each 14 day period of study drugs. |
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E.5.2 | Secondary end point(s) |
i)Difference in clinic systolic BP between paracetamol and placebo periods ii)Difference in daytime diastolic ambulatory BP between paracetamol and placebo periods iii)Difference in mean daytime systolic ambulatory BP between the paracetamol and placebo periods in patients taking and not taking antihypertensive medications
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Clinic systolic BP will be assessed on day 0, day 4&7, and day 14 of study drugs. Ambulatory BP will be assessed on day 0 and day 14 (ie start and end of study drugs). |
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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 | No |
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 | No |
E.8.1.6 | Cross over | Yes |
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.8.6 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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |