Study on the Improvement of Microcirculation in Patients With Sepsis by Vitamin B6, Vitamin B12 and Vitamin C

Обзор

Sepsis is a kind of disease with high morbidity and mortality in ICU. At present, there is no specific treatment, and its pathogenesis is mainly excessive oxidative stress. Anti-inflammatory, antioxidant and immune-regulating drugs may produce better therapeutic effects, while vitamin B6, vitamin B12 and vitamin C have anti-inflammatory, antioxidant and immune-regulating effects. The purpose of this study was to investigate whether vitamin B6, vitamin B12 combined with vitamin C can improve the microcirculation and organ dysfunction in patients with sepsis, and improve the survival rate of patients with sepsis. The study included 296 patients who met the inclusion criteria. After randomization, the experimental group was given intravenous vitamin B6 300mg qd in addition to the basic treatment of sepsis Vitamin B12 0.5mg q6h, vitamin C 50mg/kg q6h for 4 days. Control group 1 was given vitamin B6 300mg qd and vitamin B12 0.5mg q6h intravenously for 4 days. Control group 2 was injected with vitamin C 50mg/kg q6h intravenously for 4 days. Control group 3: The same dose of placebo (0.9% sodium chloride solution) was administered for 4 days. After medication, sublingual microcirculation image and radial artery resistance index of snus pit were detected and recorded according to the time required by the study protocol. The duration of use of pressor drugs, ventilator days, ICU stay, 28-day mortality, capillary refill time, changes in SOFA score and APACHEII score on day 3 and day 7 compared with baseline values at randomization, daily veno-arterial carbon dioxide differential pressure (GAP) and central venous oxygen saturation were recorded. After the end of the experiment, statistical analysis of the data was carried out to further explore the test results

Вмешательства

• Препарат vitamin B6+ Vitamin B12 +vitamin C
  In addition to the basic treatment of sepsis, intravenous injection of vitamin B6 300mg qd Vitamin B12 0.5mg q6h, vitamin C 50mg/kg q6h for 4 days.
• Препарат vitamin B6+ Vitamin B12
  In addition to the basic treatment of sepsis, vitamin B6 300mg qd and vitamin B12 0.5mg q6h were given intravenously for 4 days.
• Препарат vitamin C
  On the basis of the basic treatment of sepsis, intravenous vitamin C 50mg/kg q6h was given for 4 days.
• Препарат 0.9%Nacl
  The same dose of placebo (0.9% sodium chloride solution) was administered on top of the sepsis base treatment for 4 days.

Первичные конечные точки

• Improvement of microcirculation [Срок оценки: At 0 hour, 6hours, 24hours, 48hours, 4 days, and 7 days after initiation of administration.]
• Improvement of microcirculation [Срок оценки: At 0 hour, 6hours, 24hours, 48hours, 4 days, and 7 days after initiation of administration.]

Вторичные конечные точки (9)

• The duration of the patient's use of pressor drugs [Срок оценки: 4 days]
• Number of days on ventilator [Срок оценки: 28 days]
• ICU stay [Срок оценки: 28 days]
• 28-day mortality [Срок оценки: 28 days]
• Capillary refill time [Срок оценки: 4 days]
• Changes in SOFA score [Срок оценки: 7 days]
• Changes in APACHEII score [Срок оценки: 7 days]
• Daily change of veno-arterial carbon dioxide differential pressure (GAP) [Срок оценки: 4 days]
• Daily change of central venous oxygen saturation (Scv02) [Срок оценки: 4 days]

Критерии участия

Критерии включения

• Age ≥18 and < 85 years old
• Admitted to ICU
• Diagnosis of patients with SEPSIS 3.0 (diagnostic criteria) 4, SOFA score is 2-13 points

5\. Obtain the informed consent of the subject or his family

Критерии исключения

• Patients have absolute contraindications such as vitamin allergy
• Patients with a history of gout
• Death is expected within 24 hours
• Pregnant women
• Use hydroprednisone or other equivalent dose hormones > 200mg/d within 24 hours
• Without the informed consent of the patient or his/her representative
• Patients with a history of scleroderma
• Patients with a history of vasculitis
• Patients with oral mucosal diseases
• Patients with severe difficulty in opening their mouth and unable to detect sublingual microcirculation

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Sichuan Provincial People's Hospital — Чэнду

Публикации

• Wald EL, Badke CM, Hintz LK, Spewak M, Sanchez-Pinto LN. Vitamin therapy in sepsis. Pediatr Res. 2022 Jan;91(2):328-336. doi: 10.1038/s41390-021-01673-6. Epub 2021 Jul 31. PMID 34333556
• Giustina AD, Danielski LG, Novochadlo MM, Goldim MPS, Joaquim L, Metzker KLL, Carli RJ, Denicol T, Cidreira T, Vieira T, Petronilho F. Vitamin B6 reduces oxidative stress in lungs and liver in experimental sepsis. An Acad Bras Cienc. 2019 Dec 2;91(4):e20190434. doi: 10.1590/0001-3765201920190434. eCollection 2019. PMID 31800708
• Wang Y, Lu WL, Feng WM, Xu W, Liu LH, He LM. RENAL PROTECTIVE EFFECT AND CLINICAL ANALYSIS OF VITAMIN B 6 IN PATIENTS WITH SEPSIS. Shock. 2024 Jun 1;61(6):841-847. doi: 10.1097/SHK.0000000000002329. Epub 2024 Apr 26. PMID 38691102
• Zhao W, Zhang J, Lu Y, Wang R. The vasorelaxant effect of H(2)S as a novel endogenous gaseous K(ATP) channel opener. EMBO J. 2001 Nov 1;20(21):6008-16. doi: 10.1093/emboj/20.21.6008. PMID 11689441
• Patel JJ, Willoughby R, Peterson J, Carver T, Zelten J, Markiewicz A, Spiegelhoff K, Hipp LA, Canales B, Szabo A, Heyland DK, Stoppe C, Zielonka J, Freed JK. High-Dose IV Hydroxocobalamin (Vitamin B12) in Septic Shock: A Double-Blind, Allocation-Concealed, Placebo-Controlled Single-Center Pilot Randomized Controlled Trial (The Intravenous Hydroxocobalamin in Septic Shock Trial). Chest. 2023 Feb;16 PMID 36174744
• Fisher BJ, Seropian IM, Kraskauskas D, Thakkar JN, Voelkel NF, Fowler AA 3rd, Natarajan R. Ascorbic acid attenuates lipopolysaccharide-induced acute lung injury. Crit Care Med. 2011 Jun;39(6):1454-60. doi: 10.1097/CCM.0b013e3182120cb8. PMID 21358394
• Sevransky JE, Rothman RE, Hager DN, Bernard GR, Brown SM, Buchman TG, Busse LW, Coopersmith CM, DeWilde C, Ely EW, Eyzaguirre LM, Fowler AA, Gaieski DF, Gong MN, Hall A, Hinson JS, Hooper MH, Kelen GD, Khan A, Levine MA, Lewis RJ, Lindsell CJ, Marlin JS, McGlothlin A, Moore BL, Nugent KL, Nwosu S, Polito CC, Rice TW, Ricketts EP, Rudolph CC, Sanfilippo F, Viele K, Martin GS, Wright DW; VICTAS Inve PMID 33620405

Идентификаторы

NCT: NCT06749756 · No. 742-1in2024ofLunShen(Yan）

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗