Thiamine as a Renal Protective Agent in Septic Shock

NCT03550794 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 2018P-000204
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 4

Brief Summary

This is a randomized, double-blind, placebo controlled study to investigate the effect of intravenous thiamine (vitamin B1) on renal function in septic shock.

Conditions

Sepsis; Kidney Injury; Thiamine Deficiency

Outcome Measures

Primary Outcomes (1)

• Kidney Injury Biomarker

  Change in creatinine over time

  Enrollment to 72-hours

Secondary Outcomes (8)

• Number of Participants Receiving Renal Replacement Therapy

  From date of enrollment until discharge from the intensive care unit (ICU) or date of death, whichever comes first, up to 60 days after enrollment

• ICU Free Days

  From date of enrollment until 28 days after enrollment

• In-hospital Mortality

  From date of enrollment until discharge from the hospital or date of death, whichever comes first, up to 60 days after enrollment

• Number of Participants Experiences Acute Renal Failure

  From date of enrollment until day of discharge from the index ICU admission or date of death, whichever comes first up until 60 days post-enrollment

• Change in Lactate Level

  From time of enrollment until 72 hours after enrollment

Study Arms (2)

Thiamine

EXPERIMENTAL

200mg parenterally administered thiamine hydrochloride given twice daily for a 3 days (6 doses)

Drug: Thiamine Hydrochloride

Placebo

PLACEBO COMPARATOR

Matching placebo (50ml 0.9%NACL) given twice daily for 3 days (6 administrations)

Drug: Placebo

Interventions

Thiamine Hydrochloride DRUG

Thiamine hydrochloride is a water soluble vitamin (vitamin B1). 200mg of thiamine hydrochloride in 50ml 0.9%NACL will be administered twice daily for 3 days.

Also known as: Thiamine, Vitamin B1

Thiamine

Placebo DRUG

50ml of 0.9% NACL will serve as the placebo

Also known as: Normal Saline, 0.9%NACL

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult ≥18 years of age
• Suspected or Confirmed Infection (defined as collection of a blood/fluid culture and provision of an antimicrobial)
• Receipt of a vasopressor agent (e.g. norepinephrine, phenylephrine, vasopressin)
• Serum lactate ≥2mmol/L
• Creatinine \>1.0mg/dL

You may not qualify if:

• Clinical indication for thiamine administration (alcoholism, known or highly suspected deficiency) or treatment with thiamine beyond the amount found in a standard multivitamin within the last 10 days
• Renal replacement therapy within the past 30 days
• Comfort measures only or anticipated withdrawal of support within 24 hours
• Protected populations (pregnant women, prisoners)
• Known thiamine allergy

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead

Study Sites (4)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Northshore University Hospital

Manhasset, New York, 11030, United States

Location

Montefiore Medical Center

New York, New York, 10467, United States

Location

Long Island Jewish Hospital

Queens, New York, 11040, United States

Location

Related Publications (4)

• Moskowitz A, Andersen LW, Cocchi MN, Karlsson M, Patel PV, Donnino MW. Thiamine as a Renal Protective Agent in Septic Shock. A Secondary Analysis of a Randomized, Double-Blind, Placebo-controlled Trial. Ann Am Thorac Soc. 2017 May;14(5):737-741. doi: 10.1513/AnnalsATS.201608-656BC.

  PMID: 28207287 BACKGROUND

• Donnino MW, Andersen LW, Chase M, Berg KM, Tidswell M, Giberson T, Wolfe R, Moskowitz A, Smithline H, Ngo L, Cocchi MN; Center for Resuscitation Science Research Group. Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study. Crit Care Med. 2016 Feb;44(2):360-7. doi: 10.1097/CCM.0000000000001572.

  PMID: 26771781 BACKGROUND

• Vine J, Lee JH, Kravitz MS, Grossestreuer AV, Balaji L, Leland SB, Berlin N, Moskowitz A, Donnino MW. Thiamine administration in septic shock: a post hoc analysis of two randomized trials. Crit Care. 2024 Feb 6;28(1):41. doi: 10.1186/s13054-024-04818-1.

  PMID: 38321529 DERIVED

• Moskowitz A, Berg KM, Grossestreuer AV, Balaji L, Liu X, Cocchi MN, Chase M, Gong MN, Gong J, Parikh SM, Ngo L, Berlin N, Donnino MW. Thiamine for Renal Protection in Septic Shock (TRPSS): A Randomized, Placebo-controlled, Clinical Trial. Am J Respir Crit Care Med. 2023 Sep 1;208(5):570-578. doi: 10.1164/rccm.202301-0034OC.

  PMID: 37364280 DERIVED

MeSH Terms

Conditions

Sepsis; Thiamine Deficiency

Interventions

thiamine hydrochloride; Thiamine; Saline Solution; Sodium Chloride

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vitamin B Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Dr. Ari Moskowitz
• Organization: Montefiore Medical Center

amoskowitz@montefiore.org

7189202956

Study Officials

• Ari Moskowitz, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A randomization list will be prepared by an independent statistician using 1:1 randomization in blocks of two and four. This list will be provided to the research pharmacy, and the research pharmacy will be the only unblinded people involved with the study, and will have no patient contact or role in the analysis or other aspects of the study. Thiamine is colorless and odorless, and the 200mg dose is mixed in 5mL of normal saline. Placebo will be 50mL of normal saline and is indistinguishable in appearance from thiamine. Study team, clinical team and patient and family will all be blind to the allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Emergency Medicine

Study Record Dates

• First Submitted: May 25, 2018
• First Posted: June 8, 2018
• Study Start: September 4, 2018
• Primary Completion: April 5, 2022
• Study Completion: April 5, 2022
• Last Updated: June 27, 2023
• Results First Posted: June 27, 2023

Record last verified: 2023-06

Locations

US (4)