Evaluation of the Efficacy and Safety of Oral Nicotinamide as an Adjunctive Therapy in Patients With Sepsis
Trial Snapshot
- Phase
- Phase 4
- Status
- Not yet recruiting
- Sponsor
- Ain Shams University
- Enrollment
- 60
- Locations
- 1
Study Overview
Brief Summary
Sepsis is a severe, life-threatening condition caused by an abnormal host response to infection, which includes systemic inflammation, oxidative stress, and increasing organ dysfunction. It is frequently associated with bacterial, viral, fungal, or parasite infections, as well as non-infectious illnesses like trauma and pancreatitis. It remains a primary cause of mortality in hospitals, with rates nearing 40% in severely ill patients. pathophysiological, excessive cytokine release (e.g., TNFα, IL-6, IL-1β) and reactive oxygen/nitrogen species lead to mitochondrial injury, immunosuppression, and multiple organ failure. Sepsis diagnosis is guided byNEWS2 & a SOFA score ≥2, hypotension, and elevated lactate, while worsening SOFA scores predict poor outcomes. Standard management focusses on early antibiotic therapy, fluid resuscitation, and vasoactive support. Standard anti-inflammatory methods using steroidal or non-steroidal medicines may show little efficacy to improve the patient's clinical outcomes. Adjunctive antioxidant therapies, including vitamins C and E, NAC, and melatonin, have demonstrated reductions in oxidative stress and organ dysfunction. Nicotinamide (NAM) (vitamin B3), a precursor of NAD+/NADP+ critical for energy metabolism and cellular repair, has emerged as a potential therapeutic candidate due to its ability to attenuate cytokine production, modulate immune responses, and mitigate oxidative damage. Usual dose of NAM (500mg-1500mg per day) is generally safe. A dose of 1000 mg was found to be safe and effective in reducing the circulating inflammatory cytokines showing a good profile as an anti-inflammatory adjunct therapy. Higher than usual NAM dose can increase the likelihood of adverse effects, such as diarrhea, increased liver enzymes (rarely occurring at doses exceeding 3 grams per day), symptoms of thrombocytopenia (including increased bruising and bleeding), and stomach upset.
Since the role of NAM as adjunct therapy in sepsis management is not yet established, further large-scale clinical studies are recommended to establish its efficacy and safety in sepsis management.
The aim of our study is to evaluate the efficacy and safety of the addition of Nicotinamide (1000mg oral tablet) as an adjunct therapy to improve the outcome of septic patients.
Detailed Description
Sepsis is a life-threatening medical illness caused by the body's response to an infection, resulting in extensive inflammation. This inflammation can cause a series of changes in the body, leading to restricted blood flow to key organs, causing organ failure and eventually death. Sepsis can be caused by bacteria, viruses, fungi, or parasites, or it can develop due to noninfectious intra-abdominal causes, including severe trauma, pneumonia, pancreatitis, and urinary system infection. Despite advances in medical treatments, sepsis remains a major cause of death globally among hospitalized patients because of its complications. According to reports, Hospital mortality rates were 26% for hospital-wide sepsis and 40% for ICU sepsis. Sepsis was more common in the United States among men, non-white individuals, and the elderly (60 years and older) than among women and white persons.
Severe sepsis is characterized by one or more end-organ failures, while septic shock is characterized by hemodynamic instability despite intravascular volume replacement. The overwhelming immune response and the altered balance between pro-inflammatory and anti-inflammatory mediators contribute to the development of sepsis, making it particularly challenging to treat.
Some possible complications of sepsis include Acute/chronic renal injury, Mesenteric ischemia, Acute liver failure, Myocardial dysfunction, and Multiple organ failure. Previous studies showed that sepsis can cause the disturbance of immunological homeostasis, leading to immunosuppression in sepsis.
The SOFA (Sequential Organ Failure Assessment) score is currently advised for diagnosing both sepsis and septic shock. A diagnosis of sepsis is confirmed in the case of a (SOFA) score ≥ 2. The SOFA system is a simple technique that detects organ failure or dysfunction due to sepsis. Daily, the SOFA scoring scale allocates from 1 to 4 points for each of the following six organ systems, according to the level of dysfunction: The respiratory, circulatory, renal, hematological, hepatic, and central nervous systems. Sepsis is presented by a rise of two or more points in the SOFA score. Moreover, the SOFA score could be a method to assess morbidity in intensive care unit (ICU) sepsis patients.
Cytokines are essential for the effective functioning of critical host immune systems because they regulate the body's reactions to infection, immunological responses, inflammation, and trauma. Modifying the cytokine response is an important aspect of therapy for many severe inflammatory disorders. In septic patients, it has been demonstrated that TNFα, IL-6, and IL-1β correspond with the severity of the disease and its outcome.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Supportive Care
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients older than 18 years of any gender who were admitted to the intensive care unit
- •Diagnosed as sepsis patient with the Sequential Organ Failure Assessment (SOFA) Score described as an Increase in SOFA score ≥2 points due to infection.
Exclusion Criteria
- •Pregnant or lactating women
- •Patients who had already been taking antioxidant supplements before recruiting.
- •Patient with contraindications or reported allergies to Nicotinamide.
Investigators
Basma Ahmed ABD EL Sattar Amin
Teaching Assistant , Pharmacy Practice, Egyptian Chinese University
Ain Shams University