Vitamin C, Hydrocortisone and Thiamine in Patients With Septic Shock

NCT ID: NCT05192213

Last Updated: 2024-01-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-01
• Study Completion Date: 2022-09-19

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.

Conditions

Sepsis; Septic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Intervention

1,5 g of vitamin C every 6 hours + 200 mg of thiamine every 12 hours + 50 mg of hydrocortisone every 6 hours

For 7 days or until patient's discharge/death

Group Type: EXPERIMENTAL

Vitamin C

Intervention Type: DRUG

Patients will be allocated in a 1: 1 ratio to the treatment group, receiving intravenous Vitamin C (1.5 g every 6 hours), Thiamine (200 mg every 12 hours) and Hydrocortisone (50 mg every 6 hours) for 7 days

Control

Placebo 1 for vitamin C every 6 hours + Placebo 2 for thiamine every 12 hours + 50 mg of hydrocortisone every 6 hours

For 7 days or until patient's discharge/death

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Patients will receive 2 placebos (every 6 hours and every 12 hours) + Hydrocortisone (50 mg every 6 hours) for 7 days.

Interventions

Vitamin C

Patients will be allocated in a 1: 1 ratio to the treatment group, receiving intravenous Vitamin C (1.5 g every 6 hours), Thiamine (200 mg every 12 hours) and Hydrocortisone (50 mg every 6 hours) for 7 days

Intervention Type: DRUG

Placebo

Patients will receive 2 placebos (every 6 hours and every 12 hours) + Hydrocortisone (50 mg every 6 hours) for 7 days.

Intervention Type: OTHER

Other Intervention Names

thiamine; hydrocortisone

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PROADI-SUS

UNKNOWN

Sponsor Role: collaborator

Ministry of Health, Brazil

OTHER_GOV

Sponsor Role: collaborator

Hospital Sirio-Libanes

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Luciano CP Azevedo, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Sirio-Libanês

Gisele Queiroz, MD

Role: PRINCIPAL_INVESTIGATOR

Hospitla Sirio-Libanês

Locations

Hospital Maternidade São Vicente de Paulo

Barbalha, Ceará, Brazil

Hospital Otoclinica

Fortaleza, Ceará, Brazil

Hospital Evangélico de Vila Velha

Vila Velha, Espírito Santo, Brazil

Hospital Clínica São Roque

Ipiaú, Estado de Bahia, Brazil

Hospital Felício Rocho

Belo Horizonte, Minas Gerais, Brazil

Santa Casa de Misericordia de Passos

Passos, Minas Gerais, Brazil

Hospital Universitário de Maringá

Maringá, Paraná, Brazil

Hospital de Amor - Unidade Barretos

Barretos, São Paulo, Brazil

Hospital SEPACO

São Paulo, São Paulo, Brazil

Hospital Naval Marcílio Dias

Rio de Janeiro, , Brazil

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP

São Paulo, , Brazil

Hospital São Paulo

São Paulo, , Brazil

Countries

Brazil

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Other Identifiers

07445119.9.1001.5461

Identifier Type: OTHER

Identifier Source: secondary_id

AVAP-NG 1000

Identifier Type: -

Identifier Source: org_study_id