E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Radiocontrast-induced nephropathy |
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MedDRA Classification |
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 how oral and intravenous acetylcysteine affects renal function in healthy volunteers and people with chronic kidney disease (CKD), in the presence and absence of radiocontrast. |
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E.2.2 | Secondary objectives of the trial |
To identify a rational dose of acetylcysteine, given through the correct route, and assessed using the correct outcome measure, that can be studied in a large phase III trial of acetylcysteine in radiocontrast-induced nephropathy. |
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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 |
The study will be performed simultaneously in five groups of participants (Appendix 1), studying:
1. healthy volunteers receiving acetylcysteine PO, acetylcysteine IV, or placebo.
2. volunteers with stage III CKD receiving acetylcysteine PO, acetylcysteine IV, or placebo.
3. healthy volunteers receiving IV radiographic contrast plus acetylcysteine PO, acetylcysteine IV, or placebo.
4. patients with stage III CKD receiving radiographic contrast for elective coronary angiography plus acetylcysteine PO, acetylcysteine IV, or placebo.
5. patients with stage III CKD receiving radiographic contrast for elective CT plus acetylcysteine PO, acetylcysteine IV, or placebo.
Studies 1-3 of this protocol are randomised, placebo controlled, three-way cross-over, human volunteer studies. Each study will have three arms, participants being randomised to receive all three treatments on three different occasions:
A) placebo capsules PO, plus an IV infusion acetylcysteine in normal saline. B) acetylcysteine capsules PO, plus an infusion of normal saline. C) placebo capsules PO, plus an infusion of normal saline.
Studies 4 and 5 are randomised, placebo controlled, three-way parallel group study in patients undergoing elective coronary angiography and CT.
Participants in Studies 4 and 5 will be randomised to one arm only.
Sufficient participants will be recruited to studies 1, 2 and 3 to obtain full data on eight volunteers in each study. Sufficient participants will be recruited to study 4 to obtain full data on twenty-four patients, eight in each arm. Sixty-six patients will be recruited to study 5, twenty-two in each arm. |
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E.3 | Principal inclusion criteria |
Studies 1 & 3: Healthy male volunteers aged over 45 years, with a BMI between 22 and 40.
Study 2: Male volunteers aged over 45 years, with stable CKD stage III and a BMI between 22 and 40, not on metformin.
Study 4: Male patients aged over 45 years, with stable CKD stage III and a BMI between 22 and 40, not on metformin, undergoing elective coronary angiography.
Study 5: Male patients aged over 45 years, with stable CKD stage III and a BMI between 22 and 40, not on metformin, undergoing elective CT. |
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E.4 | Principal exclusion criteria |
Volunteers for Studies 1, 3 · lack of informed consent · age <46 years · current involvement in a clinical trial · clinically significant co-morbidity: heart failure, hypertension, known hyperlipidaemia, diabetes mellitus, coagulopathy or bleeding disorder. · thyroid disease, myasthenia gravis, asthma, atopy, or a history of allergy/sensitivity to acetylcysteine or contrast medium · current intake of prescription medicines · recent infective/inflammatory condition · blood donation during the preceding three months
Patients for Studies 2, 4 and 5 · lack of informed consent · age <46 years · current involvement in a clinical trial · thyroid disease, myasthenia gravis, asthma, atopy, or a history of allergy/sensitivity to acetylcysteine or contrast medium · current intake of metformin · recent infective/inflammatory condition · blood donation during the preceding three months |
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E.5 End points |
E.5.1 | Primary end point(s) |
Changes in RBF will be the primary outcome since we expect this measure to be the most sensitive to the effects of acetylcysteine and/or contrast administration. |
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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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Pathophysiology and mechanisms of acetylcysteine's effect on the kidney |
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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 | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Please note: Studies 1-3 are cross over studies while studies 4 and 5 are parallel group studies |
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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.8.3 |
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.8.5 | 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 | Information not present in EudraCT |
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
| |
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 | 5 |
E.8.9.1 | In the Member State concerned days | |