CLEARTOX: Development of an innovative haemodialysis method to improve dialytic clearance of protein-bound uraemic toxins

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hospices Civils De Lyon

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Investigative Techniques [E05], Diseases [C] - Male Urogenital Diseases [C12], Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Trial duration

22 Sep 2025 → ongoing

Decision date (initial)

2024-11-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

DGOS

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Compare the clearance of p-cresyl sulfate during dialysis (from H0 to H4) between a hemodialysis session with infusion of a medium-chain fatty acid emulsion (Medialipide®) and a hemodialysis session with infusion of saline.

Secondary objectives 8

1. To compare the reduction fraction of p-cresyl sulfate during dialysis between a hemodialysis session with medium-chain fatty acid emulsion infusion and a hemodialysis session with saline infusion.
2. Compare the reduction fraction and clearance of the following uremic toxins: indoxyl sulfate, hippuric acid, p-cresyl glucuronide, 3-indole acetic acid, uric acid and 3-carboxy-4-methyl-5propyl-furanpro-pionic acid, between a hemodialysis session with medium-chain fatty acid emulsion infusion and a hemodialysis session with saline infusion.
3. Evaluate tolerability of Médialipide® infusion
4. Evaluate safety of Médialipide® infusion
5. Evaluate the evolution of plasma concentrations of medium‑chain fatty acids (octanoate and decanoate) during the hemodialysis session.
6. To compare, between a hemodialysis session with infusion of a medium‑chain fatty acid emulsion and a hemodialysis session with infusion of physiological saline, the kinetics of the free and total fractions of uremic toxins throughout the hemodialysis session.
7. To compare, between a hemodialysis session with infusion of a medium‑chain fatty acid emulsion and a hemodialysis session with infusion of physiological saline, the total amount of uremic toxins eliminated at the end of the hemodialysis session.
8. Describe the evolution of the clearance of medium‑chain fatty acids (octanoate and decanoate) during the hemodialysis session.

Conditions and MedDRA coding

chronic hemodialysis patients (for more than 3 months) with no residual diuresis (<100 mL/day).

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age ≥18 years
2. On hemodialysis at a frequency of 3 4-hour sessions per week (+/- 30 minutes), for at least 1 month
3. For patients of childbearing potential, highly effective contraception (e.g. total sexual abstinence, combined hormonal contraception, bilateral tubal obstruction, etc.) is required for the entire duration of treatment. A blood pregnancy test (beta-HCG) will be performed at inclusion.
4. Patient affiliated to a social security scheme
5. Free, informed and written consent signed by the patient

Exclusion criteria 27

1. Residual diuresis > 100 mL per day
2. Patients with sepsis < 1 month
3. Patient with severe liver failure or cholestasis
4. Patient with known severe coagulopathy
5. Patient with acute thromboembolic events
6. Patient with fat embolism
7. Patient with an aggravating bleeding diathesis
8. Patient with uncompensated metabolic acidosis
9. Patient with an unstable circulatory state threatening the vital prognosis (collapse and shock)
10. Patients with unstable metabolic conditions (e.g. severe post-traumatic syndrome, coma of unknown origin)
11. Patients in the acute phase of myocardial infarction or stroke
12. Pregnant or breastfeeding
13. Patients with uncorrected disturbances of fluid and electrolyte balance, such as hypokalemia and hypotonic dehydration
14. Patients with decompensated heart failure
15. patients with acute pulmonary edema
16. Subject having participated in another interventional research study in the 30 days prior to inclusion in the study or still within 5 half-lives of the experimental product of a previous interventional research study.
17. Uncontrolled hypertension > 180/115 mmHg
18. Perdialytic hypotension requiring vascular filling > 100 mL during the last 3 sessions
19. Patient already on parenteral nutrition
20. Patient already on antivitamin K (or prescribed less than one month prior to inclusion)
21. Patient with heparin allergy or requiring hemodialysis without anticoagulant (recent hemorrhage)
22. Patients allergic to egg, soy or peanut proteins or to any of the active ingredients or excipients (glycerol, egg phospholipids for injection, a-tocopherol, sodium oleate (for pH adjustment), water for injection) of Médialipide®
23. Patients with severe hyperlipidemia or severe lipid metabolism disorders characterized by hypertriglyceridemia > 3 mmol/l
24. Patients on non-steroidal anti-inflammatory drugs
25. Patients under legal protection
26. Persons incapable of expressing their consent
27. Persons deprived of their liberty and emergency situations.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Clearance of p-Cresyl sulfate during hemodialysis. Dialysis clearance is defined as follows: Clairance = Qd X (C dialysate/C arterial) Calculated over 240 minutes with Qd corresponding to dialysate flow rate, C dialysate uremic toxin total concentration in dialysate, C arterial uremic toxin total concentration in blood taken from the arterial port of the dialyzer.

Secondary endpoints 8

1. The fraction of p-CS reduction during the hemodialysis session. The reduction fraction (RF) will be calculated according to the formula: RF (%) = ( Total concentration (t=0 min) - Total concentration (t=240 min ))/Total concentration (t= 0 min) (arterial C)
2. Clearance and reduction fraction (over 240 minutes) of other protein-bound uremic toxins during the hemodialysis session: indoxyl sulfate, hippuric acid, p-cresyl glucuronide, 3-indole acetic acid, uric acid and 3-carboxy-4-methyl-5propyl-furanpro-pionic acid.
3. Tolerance: % of patients with at least one of the following adverse events: nausea, vomiting or headache during the session.
4. Safety: % of patients with one of the following events: triglyceridemia > 4 g/L or 4.6 mmol/L at the end of the session, alteration in liver balance (ALT, ASAT, gamma GT, PAL, total bilirubin) or significant hemolysis during follow-up.
5. Kinetics of plasma concentrations of medium‑chain fatty acids (octanoate and decanoate) during the hemodialysis session (T0, T60, T120, T180, T240).
6. Free and total concentrations of uremic toxins throughout the hemodialysis session (T0, T15, T30, T45, T60, T90, T120, T180, T240) (arterial concentration).
7. Total amount of uremic toxins eliminated at the end of the hemodialysis session: mass transfer calculation Tm = R × C_sample × V_sample (R = ratio between the total dialysate flow and the sampled flow, C_sample = concentration sampled at T240, and V_sample = sampled volume). Sample flow rate = total dialysate volume / sampling duration.
8. Clearance of medium‑chain fatty acids (octanoate and decanoate) during the hemodialysis session (T0, T60, T120, T180, T240).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hospices Civils De Lyon

Sponsor organisation

Hospices Civils De Lyon

Address

3 Quai Des Celestins, Bp 2251 Bp 2251

City

Lyon Cedex 02

Postcode

69229

Country

France

Scientific contact point

Organisation

Hospices Civils De Lyon

Contact name

Pr Fitsum-Guebre EGZIABHER

Public contact point

Organisation

Hospices Civils De Lyon

Contact name

Pr Fitsum-Guebre EGZIABHER

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications