E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic kidney disease, stages 4 and 5 of the disease |
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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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To test whether chronic kidney disease patients on stages 4 and 5 of the disease can be safely prescribed a healthy diet with increased amount of potassium by concomitant use of potassium-lowering medication SZC to show improvements in patient´s satisfaction, symptoms and adherence to the target energy and protein recommendations. |
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E.2.2 | Secondary objectives of the trial |
Investigate the impact of implementing a healthy diet rich in potassium - combined with use of potassium-lowering medication to maintain plasma potassium within 3.5 to 5.0 mmol/L - in controlling plasma potassium, improving quality of life, ameliorating intestinal obstipation, maintain the dosage antihypertensives with blockade of renin-angiotensin-aldosterone system, diminishing inflammation, better control of phosphate and p-carbon dioxide levels and leading to a more healthy microbiota. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provision of signed informed consent prior to any study specific procedures;
2. Female and/or male patients;
3. Age between 18 to 85 years old;
4. Patients with chronic kidney disease under regular treatment at the outpatient clinic;
5. Glomerular filtration rate below 29 ml/min/1.73 m2 (stage 4 and 5 of the disease) and not on dialysis;
6. Plasma potassium ≥ 5.1 mmol/L at baseline or patients using of sodium polystyrene sulfonate (SPS) 1 month prior to inclusion to decrease the potassium plasma levels who develops hyperkalemia after sodium polystyrene sulfonate is discontinued;
7. Negative pregnancy test (urine or serum) for female subjects of childbearing potential;
8. Female subjects must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception (an acceptable method of contraception is defined as a barrier method in conjunction with a spermicide) for the duration of the study (from the time they sign consent) and for 3 months after the last dose of SZC to prevent pregnancy. In addition, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used.
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E.4 | Principal exclusion criteria |
1. Use of other potassium-lowering agent then SPS (loop-diuretics not included);
2. Participation in another clinical study with an investigational product during the last 3 months prior to inclusion;
3. Plasma potassium > 6.5 mmol/L;
4. Plasma potassium < 3.0 mmol/l at any visit;
5. Likely to start dialysis within 2 months according to the clinical judgment from the nephrologist;
6. Presence of inflammatory bowel syndrome;
7. Lack of fluence in the Swedish language;
8. Known hypersensitivity to SZC;
9. Known history of drug or alcohol abuse within 1 year of screening;
10. For women only - currently pregnant (confirmed with positive pregnancy test) or breast feeding;
11. History of QT prolongation associated with other medications that required discontinuation of that medication;
12. Congenital long QT syndrome;
13. Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted;
14. History of QT-prolongation: QTc(f) > 550 msec or uncontrolled atrial fibrillation.
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Patient satisfaction: based on Renal Treatment Satisfaction Questionnaire (RTSQ).
2. Symptoms: based on the symptoms list.
3. Adherence to the dietary protein and energy targets: based on the 24-hour food recalls.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The following timepoints are the same for all primary endpoints:
Baseline (Week 0), Week 3 (Beginning of healthy diet), Week 6 (End of Study, End of healthy Diet) |
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E.5.2 | Secondary end point(s) |
1. Changes in plasma potassium
2. % patients with normokalemia, defined as potassium 3.5-5.0 mmol/L
3. Quality of life parameters: based on the RAND Short Form Health Survey (SF-36)
4. Improvement of intestinal obstipation: based on the ROMA III questionnaire and Bristol stool score;
5. Changes in inflammatory markers (C-reactive protein and interleukin-6), phosphate, P-carbon dioxide.
6. Reduction of circulating levels of microbiota-derived uremic retention solutes, such as indoxyl-sulfate, p-cresyl sulfate and trimethylamine N-oxide.
7. Maintaining the desired level of dosage of ACEIs and ARBs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The following timepoints are the same for all secondary endpoints:
Baseline (Week 0), Week 3 (End of stabilization phase and beginning of healthy diet phase), Week 6 (End of Study, End of healthy Diet).
Potassium will assessed also after 48h of baseline, after 48 hours Starting Week 3 and in week 2 and week 5. |
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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 | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
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 | 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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |