Trial Outcomes & Findings for Thiamine as a Renal Protective Agent in Septic Shock (NCT NCT03550794)
NCT ID: NCT03550794
Last Updated: 2023-06-27
Results Overview
Change in creatinine over time
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
95 participants
Primary outcome timeframe
Enrollment to 72-hours
Results posted on
2023-06-27
Participant Flow
Participant milestones
| Measure |
Thiamine
200mg parenterally administered thiamine hydrochloride given twice daily for a 3 days (6 doses)
Thiamine Hydrochloride: 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.
|
Placebo
Matching placebo (50ml 0.9%NACL) given twice daily for 3 days (6 administrations)
Placebo: 50ml of 0.9% NACL will serve as the placebo
|
|---|---|---|
|
Overall Study
STARTED
|
46
|
49
|
|
Overall Study
COMPLETED
|
42
|
46
|
|
Overall Study
NOT COMPLETED
|
4
|
3
|
Reasons for withdrawal
| Measure |
Thiamine
200mg parenterally administered thiamine hydrochloride given twice daily for a 3 days (6 doses)
Thiamine Hydrochloride: 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.
|
Placebo
Matching placebo (50ml 0.9%NACL) given twice daily for 3 days (6 administrations)
Placebo: 50ml of 0.9% NACL will serve as the placebo
|
|---|---|---|
|
Overall Study
No longer met inclusion criteria
|
1
|
2
|
|
Overall Study
Goals of care changed
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
|
Overall Study
Death
|
0
|
1
|
Baseline Characteristics
Thiamine as a Renal Protective Agent in Septic Shock
Baseline characteristics by cohort
| Measure |
Thiamine
n=42 Participants
200mg parenterally administered thiamine hydrochloride given twice daily for a 3 days (6 doses)
Thiamine Hydrochloride: 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.
|
Placebo
n=46 Participants
Matching placebo (50ml 0.9%NACL) given twice daily for 3 days (6 administrations)
Placebo: 50ml of 0.9% NACL will serve as the placebo
|
Total
n=88 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
74.5 years
n=39 Participants
|
70.0 years
n=41 Participants
|
71.5 years
n=35 Participants
|
|
Sex: Female, Male
Female
|
24 Participants
n=39 Participants
|
19 Participants
n=41 Participants
|
43 Participants
n=35 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=39 Participants
|
27 Participants
n=41 Participants
|
45 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
American Indian/Native Alaskan
|
0 Participants
n=39 Participants
|
1 Participants
n=41 Participants
|
1 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=39 Participants
|
2 Participants
n=41 Participants
|
2 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Black/African American
|
3 Participants
n=39 Participants
|
6 Participants
n=41 Participants
|
9 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Not reported
|
1 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
1 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Unknown/other
|
8 Participants
n=39 Participants
|
9 Participants
n=41 Participants
|
17 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
White
|
30 Participants
n=39 Participants
|
28 Participants
n=41 Participants
|
58 Participants
n=35 Participants
|
|
Body Mass Index
|
28.6 kg/m^2
n=39 Participants
|
30.6 kg/m^2
n=41 Participants
|
28.9 kg/m^2
n=35 Participants
|
|
Past Medical History: Malignancy
|
8 Participants
n=39 Participants
|
10 Participants
n=41 Participants
|
18 Participants
n=35 Participants
|
|
Past Medical History: Coronary Artery Disease
|
10 Participants
n=39 Participants
|
8 Participants
n=41 Participants
|
18 Participants
n=35 Participants
|
|
Past Medical History: Congestive Heart Failure
|
9 Participants
n=39 Participants
|
13 Participants
n=41 Participants
|
22 Participants
n=35 Participants
|
|
Past Medical History: Liver Disease
|
0 Participants
n=39 Participants
|
6 Participants
n=41 Participants
|
6 Participants
n=35 Participants
|
|
Chronic Kidney Disease
No Kidney Disease
|
34 Participants
n=39 Participants
|
38 Participants
n=41 Participants
|
72 Participants
n=35 Participants
|
|
Chronic Kidney Disease
Stage 2
|
1 Participants
n=39 Participants
|
1 Participants
n=41 Participants
|
2 Participants
n=35 Participants
|
|
Chronic Kidney Disease
Stage 3a
|
2 Participants
n=39 Participants
|
1 Participants
n=41 Participants
|
3 Participants
n=35 Participants
|
|
Chronic Kidney Disease
Stage 3b
|
2 Participants
n=39 Participants
|
1 Participants
n=41 Participants
|
3 Participants
n=35 Participants
|
|
Chronic Kidney Disease
Stage 4
|
0 Participants
n=39 Participants
|
2 Participants
n=41 Participants
|
2 Participants
n=35 Participants
|
|
Chronic Kidney Disease
Unknown/not reported
|
3 Participants
n=39 Participants
|
3 Participants
n=41 Participants
|
6 Participants
n=35 Participants
|
|
Source of Sepsis
Endocarditis
|
0 Participants
n=39 Participants
|
2 Participants
n=41 Participants
|
2 Participants
n=35 Participants
|
|
Source of Sepsis
Infection of unknown source
|
3 Participants
n=39 Participants
|
3 Participants
n=41 Participants
|
6 Participants
n=35 Participants
|
|
Source of Sepsis
Intra-abdominal infection
|
10 Participants
n=39 Participants
|
9 Participants
n=41 Participants
|
19 Participants
n=35 Participants
|
|
Source of Sepsis
Other
|
6 Participants
n=39 Participants
|
5 Participants
n=41 Participants
|
11 Participants
n=35 Participants
|
|
Source of Sepsis
Pneumonia
|
7 Participants
n=39 Participants
|
9 Participants
n=41 Participants
|
16 Participants
n=35 Participants
|
|
Source of Sepsis
Skin or soft tissue infection
|
4 Participants
n=39 Participants
|
2 Participants
n=41 Participants
|
6 Participants
n=35 Participants
|
|
Source of Sepsis
Urinary tract infection
|
12 Participants
n=39 Participants
|
16 Participants
n=41 Participants
|
28 Participants
n=35 Participants
|
|
Volume of intravenous fluids prior to study drug
|
2000 mL
n=39 Participants
|
1819.0 mL
n=41 Participants
|
1972.5 mL
n=35 Participants
|
|
Baseline cardiovascular component of the total SOFA score
|
4 units on a scale
n=39 Participants
|
4 units on a scale
n=41 Participants
|
4 units on a scale
n=35 Participants
|
|
Time from vasopressor initiation to first study drug
|
12.8 Hours
n=39 Participants
|
14.4 Hours
n=41 Participants
|
14.1 Hours
n=35 Participants
|
|
Time from informed consent to first study drug
|
1.6 Hours
n=39 Participants
|
1.6 Hours
n=41 Participants
|
1.6 Hours
n=35 Participants
|
|
Mechanically ventilated
|
27 Participants
n=39 Participants
|
27 Participants
n=41 Participants
|
54 Participants
n=35 Participants
|
|
Lactate
|
2.9 mmol/L
n=39 Participants
|
3.1 mmol/L
n=41 Participants
|
2.9 mmol/L
n=35 Participants
|
|
30-day predicted survival
High likelihood
|
10 Participants
n=39 Participants
|
8 Participants
n=41 Participants
|
18 Participants
n=35 Participants
|
|
30-day predicted survival
Uncertain
|
29 Participants
n=39 Participants
|
37 Participants
n=41 Participants
|
66 Participants
n=35 Participants
|
|
30-day predicted survival
Low likelihood
|
3 Participants
n=39 Participants
|
1 Participants
n=41 Participants
|
4 Participants
n=35 Participants
|
PRIMARY outcome
Timeframe: Enrollment to 72-hoursChange in creatinine over time
Outcome measures
| Measure |
Placebo
n=46 Participants
Matching placebo (50ml 0.9%NACL) given twice daily for 3 days (6 administrations)
Placebo: 50ml of 0.9% NACL will serve as the placebo
|
Thiamine
n=42 Participants
200mg parenterally administered thiamine hydrochloride given twice daily for a 3 days (6 doses)
Thiamine Hydrochloride: 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.
|
|---|---|---|
|
Kidney Injury Biomarker
|
2.79 mg/dL
Standard Deviation 1.91
|
2.24 mg/dL
Standard Deviation 1.50
|
SECONDARY outcome
Timeframe: From date of enrollment until discharge from the intensive care unit (ICU) or date of death, whichever comes first, up to 60 days after enrollmentNumber of participants who received renal replacement therapy in thiamine and placebo groups.
Outcome measures
| Measure |
Placebo
n=46 Participants
Matching placebo (50ml 0.9%NACL) given twice daily for 3 days (6 administrations)
Placebo: 50ml of 0.9% NACL will serve as the placebo
|
Thiamine
n=42 Participants
200mg parenterally administered thiamine hydrochloride given twice daily for a 3 days (6 doses)
Thiamine Hydrochloride: 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.
|
|---|---|---|
|
Number of Participants Receiving Renal Replacement Therapy
|
10 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: From date of enrollment until 28 days after enrollmentDays alive and free of the ICU through day 28
Outcome measures
| Measure |
Placebo
n=46 Participants
Matching placebo (50ml 0.9%NACL) given twice daily for 3 days (6 administrations)
Placebo: 50ml of 0.9% NACL will serve as the placebo
|
Thiamine
n=42 Participants
200mg parenterally administered thiamine hydrochloride given twice daily for a 3 days (6 doses)
Thiamine Hydrochloride: 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.
|
|---|---|---|
|
ICU Free Days
|
0.0 days
Interval 0.0 to 23.0
|
22.5 days
Interval 0.0 to 25.0
|
SECONDARY outcome
Timeframe: From date of enrollment until discharge from the hospital or date of death, whichever comes first, up to 60 days after enrollmentLength of hospital stay truncated at 60 days
Outcome measures
| Measure |
Placebo
n=46 Participants
Matching placebo (50ml 0.9%NACL) given twice daily for 3 days (6 administrations)
Placebo: 50ml of 0.9% NACL will serve as the placebo
|
Thiamine
n=42 Participants
200mg parenterally administered thiamine hydrochloride given twice daily for a 3 days (6 doses)
Thiamine Hydrochloride: 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.
|
|---|---|---|
|
In-hospital Mortality
|
25 Participants
|
15 Participants
|
SECONDARY outcome
Timeframe: 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-enrollmentAcute renal failure as defined by the KDIGO (Kidney Disease Improving Global Outcomes) AKI (Acute Kidney Injury) criteria. In brief, a patient can meet these criteria if their serum creatinine increases (for example, serum creatinine increases to 1.5x or higher of baseline serum creatinine, or if it crosses 4mg/dL), or if renal replacement therapy is initiated, or if urine output decreases (for example, \<0.5ml/kg/hour for 6-12 hours) or if patient becomes anuric (no urine production).
Outcome measures
| Measure |
Placebo
n=46 Participants
Matching placebo (50ml 0.9%NACL) given twice daily for 3 days (6 administrations)
Placebo: 50ml of 0.9% NACL will serve as the placebo
|
Thiamine
n=42 Participants
200mg parenterally administered thiamine hydrochloride given twice daily for a 3 days (6 doses)
Thiamine Hydrochloride: 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.
|
|---|---|---|
|
Number of Participants Experiences Acute Renal Failure
|
34 Participants
|
23 Participants
|
SECONDARY outcome
Timeframe: From time of enrollment until 72 hours after enrollmentChange in lactate level between enrollment and 72 hours after enrollment
Outcome measures
| Measure |
Placebo
n=46 Participants
Matching placebo (50ml 0.9%NACL) given twice daily for 3 days (6 administrations)
Placebo: 50ml of 0.9% NACL will serve as the placebo
|
Thiamine
n=42 Participants
200mg parenterally administered thiamine hydrochloride given twice daily for a 3 days (6 doses)
Thiamine Hydrochloride: 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.
|
|---|---|---|
|
Change in Lactate Level
|
1.95 mmol/L
Interval 1.4 to 2.3
|
1.65 mmol/L
Interval 1.1 to 2.8
|
SECONDARY outcome
Timeframe: Day 3 after enrollmentPopulation: Excludes 8 and 4 patients in intervention and placebo groups with delirium status "unable to assess"
Number of Participants with Delirium on Day 3 after enrollment
Outcome measures
| Measure |
Placebo
n=42 Participants
Matching placebo (50ml 0.9%NACL) given twice daily for 3 days (6 administrations)
Placebo: 50ml of 0.9% NACL will serve as the placebo
|
Thiamine
n=34 Participants
200mg parenterally administered thiamine hydrochloride given twice daily for a 3 days (6 doses)
Thiamine Hydrochloride: 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.
|
|---|---|---|
|
Number of Participants With Delirium on Day 3
|
30 Participants
|
25 Participants
|
SECONDARY outcome
Timeframe: Time of enrollment until 72 hours after enrollmentChange in Sequential Organ Failure Assessment Score (SOFA) score between enrollment and 72 hours after enrollment. SOFA scores are reported on a scale between 0-24, with 0 representing best outcome and 24 representing worst outcome.
Outcome measures
| Measure |
Placebo
n=46 Participants
Matching placebo (50ml 0.9%NACL) given twice daily for 3 days (6 administrations)
Placebo: 50ml of 0.9% NACL will serve as the placebo
|
Thiamine
n=42 Participants
200mg parenterally administered thiamine hydrochloride given twice daily for a 3 days (6 doses)
Thiamine Hydrochloride: 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.
|
|---|---|---|
|
Change in the Sequential Organ Failure Assessment Score
|
9.61 units on a scale
Standard Deviation 5.96
|
8.09 units on a scale
Standard Deviation 5.60
|
SECONDARY outcome
Timeframe: 24 hours after enrollmentPopulation: A total of 32 patients in thiamine and 37 patients in placebo had biomarkers available at both 0 hours and 24 hours and thus contributed to the model estimates
KIM-1, NGAL, Cystatin-C at 24-hours after enrollment
Outcome measures
| Measure |
Placebo
n=37 Participants
Matching placebo (50ml 0.9%NACL) given twice daily for 3 days (6 administrations)
Placebo: 50ml of 0.9% NACL will serve as the placebo
|
Thiamine
n=32 Participants
200mg parenterally administered thiamine hydrochloride given twice daily for a 3 days (6 doses)
Thiamine Hydrochloride: 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.
|
|---|---|---|
|
Novel Biomarkers of Renal Injury
KIM-1
|
793.9 pg/mL
Interval 350.6 to 1548.8
|
763.1 pg/mL
Interval 454.8 to 1504.8
|
|
Novel Biomarkers of Renal Injury
NGAL
|
1558285.0 pg/mL
Interval 966335.0 to 3235305.6
|
1067898.2 pg/mL
Interval 501797.2 to 1528804.4
|
|
Novel Biomarkers of Renal Injury
Cystatin
|
2183175.4 pg/mL
Interval 1614104.4 to 2819738.6
|
1689158.2 pg/mL
Interval 1238353.1 to 2677488.6
|
Adverse Events
Thiamine
Serious events: 0 serious events
Other events: 0 other events
Deaths: 15 deaths
Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 25 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place