Efficacy and tolerance of nicotinamide supplementation during acute kidney injury: a prospective randomized double-blind trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Marseille

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Decision date (initial)

2025-05-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Assistance Publique–Hôpitaux de Marseille

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To demonstrate the superiority of nicotinamide (NAM) to achieve the complete renal recovery in patients with a persistent acute kidney injury (stage 2 or 3 in KDIGO classification) despite 24h with standard care, between two therapeutic strategies:
1) Administration of NAM
2) Standard of care

Secondary objectives 5

1. To assess the interest of NAM in terms of Clinical outcomes (1. Complete renal recovery from acute kidney disease (AKD) at day 30, 60 and 90 post randomization (3). 2. Peak creatinine in the first 21 days past treatment initiation. 3. Incidence of new dialysis over the study period. 4. Duration of renal replacement therapy over the study period. 5. Dialysis-free survival at day 30, 60, 90 post randomization. 6. ICU length of stay and in hospital stay. 7. ICU-free day(s). 8. Relapse AKI (see secondary endpoint definition).)
2. To assess the interest of NAM in terms of tolerance (1. Safety of NAM use during the treatment period.)
3. To assess the interest of NAM in terms of medico-economic impact (1. Efficiency of NAM supplementation compared to standard of care in reducing healthcare costs and improving health benefits.)
4. To assess the interest of NAM in terms of prognosis (1. Global mortality. 2. In-hospital mortality. 3. Incidence of new CKD. 4. Incidence of new ESRD.)
5. To assess the interest of NAM in terms of Pathophysiology (1. Changes from baseline in serum and urine concentration of relevant metabolites of NAD+ and tryptophan and further in resetting of the seric metabolome. 2. Prognosis value of seric and urinary nicotinamide metabolites, particularly quinolinate/triptophane ratio 3. Identification of genetic variants associated with poor or complete AKI recovery and response to NAM supplementation.

Conditions and MedDRA coding

Acute kidney injury

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Admitted to an adult intensive care unit of nephrology or Nephrology department
2. Age 18 years or more
3. Persistent acute kidney injury stage 2 or 3 in KDIGO classification despite 24h with standard care to treat pre-renal acute kidney injury according Acute Disease Quality Initiative (ADQI) workgroup
4. Suspected acute tubular necrosis as primary cause of acute kidney injury
5. Free from mechanical ventilation; hemodynamic support and non-invasive ventilation are allowed
6. Subject affiliated to or beneficiary of a social security system
7. Subject having signed written informed consent

Exclusion criteria 20

1. Acute kidney injury stage 1 (due to a very high rate of renal recovery and no potential impact of nicotinamide) in accordance with the 2019 reviews
2. Acute kidney disease (AKD) defined by AKI persisting more than 7 days and less than 3 months according ADQI workgroup
3. End stage renal disease with chronic renal replacement therapy (intermittent hemodialysis or peritoneal dialysis)
4. Chronic kidney disease with glomerular filtration rate ≤ 15 ml/min/1.73m2
5. History of kidney transplantation
6. Mechanical ventilation
7. Conditions requiring vitamin B3 supplementation: Nutritional deficiency or alcohol abuse.
8. Multiple organ dysfunction syndrome (MODS) based on modified Surviving Sepsis Campaign criteria (21). Patients with two or more organ dysfunctions other than kidney dysfunction will be categorized as having MODS. Respiratory dysfunction is defined as a PaO2/FiO2 ratio <200 and requiring mechanical ventilation. Shock status is defined as hypotension (systolic blood pressure <90 mm Hg or mean arterial pressure <70 mm Hg) that requires the use of norepinephrine > 15 μg/min. Hepatic dysfunction is defined as serum bilirubin level >2 mg/dL. Hematologic dysfunction is defined as a blood platelet count <100,000/μL. Coagulopathy is defined as an international normalized ratio >1.5. Metabolic dysfunction is defined as a serum lactate level >2 mmol/L.
9. Primary cause of AKI other than suspected ATN (renal obstruction, glomerulonephritis, immuno-allergic nephritis).
10. Moribund status (defined by the expectation of death in less than three months)
11. Liver failure (to prevent NAM liver toxicity) according to the definition in MODS above)
12. Thrombocytopenia < 50 G/L (which might occur in patients requiring dialysis and receiving NAM)
13. Known allergy to NAM
14. Taking supplemental nicotinamide or niacin (other nicotinamide supplements to be ceased 4 weeks prior to study randomization)
15. Ongoing participation in a concurrent interventional study
16. Pregnancy or breastfeeding and all other categories of people with special protection according to the French Code de la Santé Publique (CSP): patients under legal supervision, patients hospitalized without content, patients admitted in social or sanitary structures for care and not research, and patients in emergency situations
17. Severe cognitive or psychiatric disorders
18. Inability to provide informed consent, or unwillingness to participate in the study
19. Patients with limited French proficiency
20. Patients not in capacity to consent and without legal representatives present to receive information and consent for the participation of the patient

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. rate of complete renal recovery (success) assessed at day + 21 post-randomization. The complete renal recovery, (success) will be defined from the estimated glomerular filtration rate (eGFR): - if baseline eGFR is unknown; an eGFR >60ml/min (at day+21 according to the mention above) - if baseline eGFR is available; by the return to baseline eGFR +/- 3.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Marseille

Sponsor organisation

Assistance Publique Hopitaux De Marseille

Address

80 Rue Brochier

City

Marseille

Postcode

13005

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Marseille

Contact name

nephrologist

Public contact point

Organisation

Assistance Publique Hopitaux De Marseille

Contact name

nephrologist

Locations

1 EU/EEA country · 10 investigational sites

By country

Investigational sites

Results and documents

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

Documents 12 files

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

Application history

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