Clinical trial NCT05192213: Vitamin C, Hydrocortisone and Thiamine in Patients With Septic Shock
Official title: Vitamin C, Hydrocortisone and Thiamine in Patients With Septic Shock: a Randomized Clinical Study (VITAMIN TRIAL)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Sepsis
Septic Shock
Keywords: sepsis
septic shock
vitamin C
thiamine
ICU
Lead sponsor: Hospital Sirio-Libanes
Sponsor class: OTHER
Collaborators: name: PROADI-SUS
name: Ministry of Health, Brazil
First posted: 2022-01-14
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A great interest exists regarding substances with an immunomodulatory effect for sepsis patients. Recent data have shown that intravenous vitamin C, together with corticosteroids and thiamine, could prevent progressive organ dysfunction and reduce vasopressor use in patients with severe sepsis and septic shock. Its effect on mortality, on the other hand, is yet to be demonstrated. The Vitamins study aims to conclusively determine, through its prospective, multicentre and double-blinded design including 1090 patients, wether Vitamin C, Thiamine and Hydrocortisone in combination can reduce mortality in patients with septic shock.

Detailed description: The global burden of sepsis is substantial with an estimated 15 to 19 million cases per year, most occurring in low-income countries. With recent advances in diagnosis and supportive treatment, the 28-day mortality from sepsis in high-income countries has decreased by about 25%; however, the mortality from septic shock still remains around 45%.

A large volume of experimental data has shown that both corticosteroids and intravenous vitamin C attenuate the release of pro-inflammatory mediators, reduce the endothelial lesion characteristic of sepsis (reducing endothelial permeability and improving microcirculatory flow), increase the release of endogenous catecholamines and improve vasopressor reaction. In animal models, these effects resulted in reduced organ damage and increased survival. However, its effect on critically ill humans is controvert. Results of a retrospective study brought that the early use of intravenous vitamin C, together with corticosteroids and thiamine, can prevent progressive organ dysfunction and can reduce mortality in patients with severe sepsis and septic shock.

For this reason, the investigators propose a randomized, controlled, multicentre (mcRCT), pragmatic and feasibility study to investigate whether Vitamin C (1.5g 6 / 6h), along with thiamine (200 mg, 12 / 12h) and hydrocortisone (50 mg 6 / 6h) for 7 days can reduce all-cause mortality within 28 days after randomization.

Eligibility criteria: Inclusion Criteria:

* Above 18 years of age
* Sepsis of any background
* Vasopressor-dependent sepsis for at least 2 hours and vasopressor dose ≥ 0.25 µg / kg / min

Exclusion Criteria:

* Pregnancy;
* Requests for DNR (do not resuscitate) / DNI (do not intubate);
* Death is considered imminent or inevitable during this hospitalization and the attending physician, patient or substitute decision maker is not committed to active treatment;
* Patients with acute cerebral vascular event, acute coronary syndrome, active gastrointestinal bleeding, burn or trauma at admission;
* Patients with known HIV infection;
* Patients with known glucose-6 phosphate dehydrogenase (G-6PD) deficiency;
* Patients with septic shock transferred from another ICU or hospital with characteristics of septic shock for\> 12 hours;
* Patients with septic shock characteristics for\> 12 hours;
* Patients with a known history of oxalate nephropathy;
* Patients with short bowel syndrome or severe known fat malabsorption;
* Patients with acute beriberi disease;
* Patients with acute Wernicke's encephalopathy;
* Patients with known malaria;
* Patients with known or suspected scurvy;
* Patients with known or suspected Addison's disease;
* Patients with known Cushing's disease;
* Physician expects to prescribe or the patient has previously used (less than 15 days) systemic glucocorticoids for an indication other than septic shock (not including nebulized or inhaled corticosteroids), including the use of glucocorticoids for COVID-19;
* The patient is receiving treatment for systemic fungal infection or has documented Strongyloides infection at the time of randomization;
* Patient with known chronic iron overload due to iron storage and other diseases;
* Patient previously enrolled in this study.

Primary outcomes:
measure: 28-day Mortality
timeFrame: 28 days
Secondary outcomes:
measure: 90-day Mortality
timeFrame: 90 days
measure: Duration of support
timeFrame: 28 days
measure: Delta SOFA
timeFrame: 72 hours
measure: Quality of life assessment
timeFrame: 6 months
Other outcomes:
measure: Duration of hospital stay
timeFrame: Until hospital discharge or up to 90 days of randomisation
measure: Changes in Inflammatory Markers
timeFrame: Up to 96 hours of randomisation
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 28 days
Locations:
city: Ipiaú
country: Brazil
facility: Hospital Clínica São Roque
state: Bahia
city: Fortaleza
country: Brazil
facility: Hospital Otoclinica
state: Ceara
city: Barbalha
country: Brazil
facility: Hospital Maternidade São Vicente de Paulo
state: Ceará
city: Vila Velha
country: Brazil
facility: Hospital Evangélico de Vila Velha
state: Espirito Santo
city: Belo Horizonte
country: Brazil
facility: Hospital Felício Rocho
state: Minas Gerais
city: Passos
country: Brazil
facility: Santa Casa de Misericordia de Passos
state: Minas Gerais
city: Maringá
country: Brazil
facility: Hospital Universitário de Maringá
state: Paraná
city: Barretos
country: Brazil
facility: Hospital de Amor - Unidade Barretos
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Hospital SEPACO
state: SP
city: Rio De Janeiro
country: Brazil
facility: Hospital Naval Marcílio Dias
city: São Paulo
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP
city: São Paulo
country: Brazil
facility: Hospital São Paulo
Study officials:
affiliation: Hospital Sirio-Libanês
name: Luciano CP Azevedo, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospitla Sirio-Libanês
name: Gisele Queiroz, MD
role: PRINCIPAL_INVESTIGATOR
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