Trial Outcomes & Findings for HAT for the Treatment of Sepsis Associated With NASTI (NCT NCT05157360)
NCT ID: NCT05157360
Last Updated: 2024-07-24
Results Overview
Hospital survival is a binary variable showing whether the patient survived their time in the hospital. Hospital survival will be assessed from date of randomization until the date of discharge or date of death from any cause, whichever comes first, assessed up to 24 months.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
10 participants
Primary outcome timeframe
Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days.
Results posted on
2024-07-24
Participant Flow
Participant milestones
| Measure |
Treatment Arm
Patients will be enrolled within 24 hours of diagnosis of sepsis related to a necrotizing soft-tissue infections (NSTI). HAT will be initiated within 4 hours of enrollment (thus treatment with HAT can occur no later than 28 hours from diagnosis).
Per Dr. Marik's original study, HAT consists of:
1. 1.5 g vitamin C every 6 hours for 4 days or until ICU discharge
2. 50 mg hydrocortisone every 6 hours for 7 days or until ICU discharge (followed by a taper over 3 days)
3. 200 mg thiamine every 12 hours for 4 days or until ICU discharge In our study, due to the prolonged ICU course typical of most patients with NSTIs, it is not felt feasible to continue indefinitely "until ICU discharge." Thus, treatment will be continued for 4 to 7 days plus a 3 day taper (respectively) as above, with no plan for a longer duration of treatment.
HAT: hydrocortisone, ascorbic acid (vitamin C), and thiamine (vitamin B1); referred to as HAT
|
Control Arm
The control arm will receive the same standard ICU care for NSTI but will not receive HAT. They will receive a placebo consisting of normal saline, indistinguishable to the treatment team (blinded) but known to the pharmacy team (unblinded to treatment and placebo groups). This is so that if the treatment team elects to give stress dose steroids, they can be administered without breaking protocol (i.e. if the patient is getting HAT, it includes steroids, so if the treating team wanted to start hydrocortisone - because they didn't know if the patient was on HAT or placebo and felt steroids were indicated - the pharmacist could ensure the patient was on steroids one way or another without unblinding the providers).
Placebo: normal saline solution
|
|---|---|---|
|
Overall Study
STARTED
|
5
|
5
|
|
Overall Study
COMPLETED
|
5
|
5
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Treatment Arm
n=5 Participants
Patients will be enrolled within 24 hours of diagnosis of sepsis related to a necrotizing soft-tissue infections (NSTI). HAT will be initiated within 4 hours of enrollment (thus treatment with HAT can occur no later than 28 hours from diagnosis).
Per Dr. Marik's original study, HAT consists of:
1. 1.5 g vitamin C every 6 hours for 4 days or until ICU discharge
2. 50 mg hydrocortisone every 6 hours for 7 days or until ICU discharge (followed by a taper over 3 days)
3. 200 mg thiamine every 12 hours for 4 days or until ICU discharge In our study, due to the prolonged ICU course typical of most patients with NSTIs, it is not felt feasible to continue indefinitely "until ICU discharge." Thus, treatment will be continued for 4 to 7 days plus a 3 day taper (respectively) as above, with no plan for a longer duration of treatment.
HAT: hydrocortisone, ascorbic acid (vitamin C), and thiamine (vitamin B1); referred to as HAT
|
Control Arm
n=5 Participants
The control arm will receive the same standard ICU care for NSTI but will not receive HAT. They will receive a placebo consisting of normal saline, indistinguishable to the treatment team (blinded) but known to the pharmacy team (unblinded to treatment and placebo groups). This is so that if the treatment team elects to give stress dose steroids, they can be administered without breaking protocol (i.e. if the patient is getting HAT, it includes steroids, so if the treating team wanted to start hydrocortisone - because they didn't know if the patient was on HAT or placebo and felt steroids were indicated - the pharmacist could ensure the patient was on steroids one way or another without unblinding the providers).
Placebo: normal saline solution
|
Total
n=10 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
66.0 years
n=5 Participants
|
54.0 years
n=5 Participants
|
60.5 years
n=10 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
1 Participants
n=5 Participants
|
4 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
4 Participants
n=5 Participants
|
6 Participants
n=10 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
United States
|
5 participants
n=5 Participants
|
5 participants
n=5 Participants
|
10 participants
n=10 Participants
|
PRIMARY outcome
Timeframe: Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days.Hospital survival is a binary variable showing whether the patient survived their time in the hospital. Hospital survival will be assessed from date of randomization until the date of discharge or date of death from any cause, whichever comes first, assessed up to 24 months.
Outcome measures
| Measure |
Treatment Arm
n=5 Participants
Patients will be enrolled within 24 hours of diagnosis of sepsis related to a necrotizing soft-tissue infections (NSTI). HAT will be initiated within 4 hours of enrollment (thus treatment with HAT can occur no later than 28 hours from diagnosis).
Per Dr. Marik's original study, HAT consists of:
1. 1.5 g vitamin C every 6 hours for 4 days or until ICU discharge
2. 50 mg hydrocortisone every 6 hours for 7 days or until ICU discharge (followed by a taper over 3 days)
3. 200 mg thiamine every 12 hours for 4 days or until ICU discharge In our study, due to the prolonged ICU course typical of most patients with NSTIs, it is not felt feasible to continue indefinitely "until ICU discharge." Thus, treatment will be continued for 4 to 7 days plus a 3 day taper (respectively) as above, with no plan for a longer duration of treatment.
HAT: hydrocortisone, ascorbic acid (vitamin C), and thiamine (vitamin B1); referred to as HAT
|
Control Arm
n=5 Participants
The control arm will receive the same standard ICU care for NSTI but will not receive HAT. They will receive a placebo consisting of normal saline, indistinguishable to the treatment team (blinded) but known to the pharmacy team (unblinded to treatment and placebo groups). This is so that if the treatment team elects to give stress dose steroids, they can be administered without breaking protocol (i.e. if the patient is getting HAT, it includes steroids, so if the treating team wanted to start hydrocortisone - because they didn't know if the patient was on HAT or placebo and felt steroids were indicated - the pharmacist could ensure the patient was on steroids one way or another without unblinding the providers).
Placebo: normal saline solution
|
|---|---|---|
|
Hospital Survival
|
2 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days.The duration of vasopressor therapy is measured after date of randomization in hours and minutes from the initiation of vasopressor therapy until the termination of vasopressor therapy.
Outcome measures
| Measure |
Treatment Arm
n=5 Participants
Patients will be enrolled within 24 hours of diagnosis of sepsis related to a necrotizing soft-tissue infections (NSTI). HAT will be initiated within 4 hours of enrollment (thus treatment with HAT can occur no later than 28 hours from diagnosis).
Per Dr. Marik's original study, HAT consists of:
1. 1.5 g vitamin C every 6 hours for 4 days or until ICU discharge
2. 50 mg hydrocortisone every 6 hours for 7 days or until ICU discharge (followed by a taper over 3 days)
3. 200 mg thiamine every 12 hours for 4 days or until ICU discharge In our study, due to the prolonged ICU course typical of most patients with NSTIs, it is not felt feasible to continue indefinitely "until ICU discharge." Thus, treatment will be continued for 4 to 7 days plus a 3 day taper (respectively) as above, with no plan for a longer duration of treatment.
HAT: hydrocortisone, ascorbic acid (vitamin C), and thiamine (vitamin B1); referred to as HAT
|
Control Arm
n=5 Participants
The control arm will receive the same standard ICU care for NSTI but will not receive HAT. They will receive a placebo consisting of normal saline, indistinguishable to the treatment team (blinded) but known to the pharmacy team (unblinded to treatment and placebo groups). This is so that if the treatment team elects to give stress dose steroids, they can be administered without breaking protocol (i.e. if the patient is getting HAT, it includes steroids, so if the treating team wanted to start hydrocortisone - because they didn't know if the patient was on HAT or placebo and felt steroids were indicated - the pharmacist could ensure the patient was on steroids one way or another without unblinding the providers).
Placebo: normal saline solution
|
|---|---|---|
|
Duration of Vasopressor Therapy
|
53.8 hours
Interval 13.3 to 198.7
|
34.6 hours
Interval 14.7 to 88.0
|
SECONDARY outcome
Timeframe: Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days.This is a binary variable the will record whether the patient did or did not have a requirement for renal replacement therapy in patients with Acute Kidney Injury (AKI).
Outcome measures
| Measure |
Treatment Arm
n=5 Participants
Patients will be enrolled within 24 hours of diagnosis of sepsis related to a necrotizing soft-tissue infections (NSTI). HAT will be initiated within 4 hours of enrollment (thus treatment with HAT can occur no later than 28 hours from diagnosis).
Per Dr. Marik's original study, HAT consists of:
1. 1.5 g vitamin C every 6 hours for 4 days or until ICU discharge
2. 50 mg hydrocortisone every 6 hours for 7 days or until ICU discharge (followed by a taper over 3 days)
3. 200 mg thiamine every 12 hours for 4 days or until ICU discharge In our study, due to the prolonged ICU course typical of most patients with NSTIs, it is not felt feasible to continue indefinitely "until ICU discharge." Thus, treatment will be continued for 4 to 7 days plus a 3 day taper (respectively) as above, with no plan for a longer duration of treatment.
HAT: hydrocortisone, ascorbic acid (vitamin C), and thiamine (vitamin B1); referred to as HAT
|
Control Arm
n=5 Participants
The control arm will receive the same standard ICU care for NSTI but will not receive HAT. They will receive a placebo consisting of normal saline, indistinguishable to the treatment team (blinded) but known to the pharmacy team (unblinded to treatment and placebo groups). This is so that if the treatment team elects to give stress dose steroids, they can be administered without breaking protocol (i.e. if the patient is getting HAT, it includes steroids, so if the treating team wanted to start hydrocortisone - because they didn't know if the patient was on HAT or placebo and felt steroids were indicated - the pharmacist could ensure the patient was on steroids one way or another without unblinding the providers).
Placebo: normal saline solution
|
|---|---|---|
|
Requirement for Renal Replacement Therapy in Patients With Acute Kidney Injury (AKI)
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days.ICU LOS will be measured by the date and time the patient was admitted to the ICU and by the date and time the patient was discharged from the ICU.
Outcome measures
| Measure |
Treatment Arm
n=5 Participants
Patients will be enrolled within 24 hours of diagnosis of sepsis related to a necrotizing soft-tissue infections (NSTI). HAT will be initiated within 4 hours of enrollment (thus treatment with HAT can occur no later than 28 hours from diagnosis).
Per Dr. Marik's original study, HAT consists of:
1. 1.5 g vitamin C every 6 hours for 4 days or until ICU discharge
2. 50 mg hydrocortisone every 6 hours for 7 days or until ICU discharge (followed by a taper over 3 days)
3. 200 mg thiamine every 12 hours for 4 days or until ICU discharge In our study, due to the prolonged ICU course typical of most patients with NSTIs, it is not felt feasible to continue indefinitely "until ICU discharge." Thus, treatment will be continued for 4 to 7 days plus a 3 day taper (respectively) as above, with no plan for a longer duration of treatment.
HAT: hydrocortisone, ascorbic acid (vitamin C), and thiamine (vitamin B1); referred to as HAT
|
Control Arm
n=5 Participants
The control arm will receive the same standard ICU care for NSTI but will not receive HAT. They will receive a placebo consisting of normal saline, indistinguishable to the treatment team (blinded) but known to the pharmacy team (unblinded to treatment and placebo groups). This is so that if the treatment team elects to give stress dose steroids, they can be administered without breaking protocol (i.e. if the patient is getting HAT, it includes steroids, so if the treating team wanted to start hydrocortisone - because they didn't know if the patient was on HAT or placebo and felt steroids were indicated - the pharmacist could ensure the patient was on steroids one way or another without unblinding the providers).
Placebo: normal saline solution
|
|---|---|---|
|
ICU Length of Stay (LOS)
|
10.0 days
Interval 7.5 to 12.0
|
7.0 days
Interval 4.0 to 10.0
|
SECONDARY outcome
Timeframe: Over the first 72 hours from admission.This is a binary variable that will show whether there was a decrease in serum procalcitonin (PCT) over first 72 hours.
Outcome measures
| Measure |
Treatment Arm
n=5 Participants
Patients will be enrolled within 24 hours of diagnosis of sepsis related to a necrotizing soft-tissue infections (NSTI). HAT will be initiated within 4 hours of enrollment (thus treatment with HAT can occur no later than 28 hours from diagnosis).
Per Dr. Marik's original study, HAT consists of:
1. 1.5 g vitamin C every 6 hours for 4 days or until ICU discharge
2. 50 mg hydrocortisone every 6 hours for 7 days or until ICU discharge (followed by a taper over 3 days)
3. 200 mg thiamine every 12 hours for 4 days or until ICU discharge In our study, due to the prolonged ICU course typical of most patients with NSTIs, it is not felt feasible to continue indefinitely "until ICU discharge." Thus, treatment will be continued for 4 to 7 days plus a 3 day taper (respectively) as above, with no plan for a longer duration of treatment.
HAT: hydrocortisone, ascorbic acid (vitamin C), and thiamine (vitamin B1); referred to as HAT
|
Control Arm
n=5 Participants
The control arm will receive the same standard ICU care for NSTI but will not receive HAT. They will receive a placebo consisting of normal saline, indistinguishable to the treatment team (blinded) but known to the pharmacy team (unblinded to treatment and placebo groups). This is so that if the treatment team elects to give stress dose steroids, they can be administered without breaking protocol (i.e. if the patient is getting HAT, it includes steroids, so if the treating team wanted to start hydrocortisone - because they didn't know if the patient was on HAT or placebo and felt steroids were indicated - the pharmacist could ensure the patient was on steroids one way or another without unblinding the providers).
Placebo: normal saline solution
|
|---|---|---|
|
Change in Serum Procalcitonin (PCT) Over First 72 Hours
|
3 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days.This is a binary variable that will shows whether there was a decrease in SOFA score over the first 72 hours (measured as SOFA score daily for four days, with day one being admission, then 3 days after, totaling 4 days of treatment with HAT).
Outcome measures
| Measure |
Treatment Arm
n=5 Participants
Patients will be enrolled within 24 hours of diagnosis of sepsis related to a necrotizing soft-tissue infections (NSTI). HAT will be initiated within 4 hours of enrollment (thus treatment with HAT can occur no later than 28 hours from diagnosis).
Per Dr. Marik's original study, HAT consists of:
1. 1.5 g vitamin C every 6 hours for 4 days or until ICU discharge
2. 50 mg hydrocortisone every 6 hours for 7 days or until ICU discharge (followed by a taper over 3 days)
3. 200 mg thiamine every 12 hours for 4 days or until ICU discharge In our study, due to the prolonged ICU course typical of most patients with NSTIs, it is not felt feasible to continue indefinitely "until ICU discharge." Thus, treatment will be continued for 4 to 7 days plus a 3 day taper (respectively) as above, with no plan for a longer duration of treatment.
HAT: hydrocortisone, ascorbic acid (vitamin C), and thiamine (vitamin B1); referred to as HAT
|
Control Arm
n=5 Participants
The control arm will receive the same standard ICU care for NSTI but will not receive HAT. They will receive a placebo consisting of normal saline, indistinguishable to the treatment team (blinded) but known to the pharmacy team (unblinded to treatment and placebo groups). This is so that if the treatment team elects to give stress dose steroids, they can be administered without breaking protocol (i.e. if the patient is getting HAT, it includes steroids, so if the treating team wanted to start hydrocortisone - because they didn't know if the patient was on HAT or placebo and felt steroids were indicated - the pharmacist could ensure the patient was on steroids one way or another without unblinding the providers).
Placebo: normal saline solution
|
|---|---|---|
|
Change in Sequential Organ Failure Assessment (SOFA) Score Over First 72 Hours (Measured as SOFA Score Daily for Four Days, With Day One Being Admission, Then 3 Days After, Totaling 4 Days of Treatment With HAT)
|
4 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days.Procalcitonin clearance (formula = initial PCT - 72 hour PCT divided by initial PCT x 100). The reported measure is median and range for those patients that
Outcome measures
| Measure |
Treatment Arm
n=5 Participants
Patients will be enrolled within 24 hours of diagnosis of sepsis related to a necrotizing soft-tissue infections (NSTI). HAT will be initiated within 4 hours of enrollment (thus treatment with HAT can occur no later than 28 hours from diagnosis).
Per Dr. Marik's original study, HAT consists of:
1. 1.5 g vitamin C every 6 hours for 4 days or until ICU discharge
2. 50 mg hydrocortisone every 6 hours for 7 days or until ICU discharge (followed by a taper over 3 days)
3. 200 mg thiamine every 12 hours for 4 days or until ICU discharge In our study, due to the prolonged ICU course typical of most patients with NSTIs, it is not felt feasible to continue indefinitely "until ICU discharge." Thus, treatment will be continued for 4 to 7 days plus a 3 day taper (respectively) as above, with no plan for a longer duration of treatment.
HAT: hydrocortisone, ascorbic acid (vitamin C), and thiamine (vitamin B1); referred to as HAT
|
Control Arm
n=5 Participants
The control arm will receive the same standard ICU care for NSTI but will not receive HAT. They will receive a placebo consisting of normal saline, indistinguishable to the treatment team (blinded) but known to the pharmacy team (unblinded to treatment and placebo groups). This is so that if the treatment team elects to give stress dose steroids, they can be administered without breaking protocol (i.e. if the patient is getting HAT, it includes steroids, so if the treating team wanted to start hydrocortisone - because they didn't know if the patient was on HAT or placebo and felt steroids were indicated - the pharmacist could ensure the patient was on steroids one way or another without unblinding the providers).
Placebo: normal saline solution
|
|---|---|---|
|
Procalcitonin Clearance
|
23.5 percentage of decrease in procalcitonin
Interval -23.6 to 78.2
|
77.9 percentage of decrease in procalcitonin
Interval -655.6 to 83.8
|
SECONDARY outcome
Timeframe: Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days.This is a variable that will show the count of wound related surgeries during the time the patient is admitted to the hospital.
Outcome measures
| Measure |
Treatment Arm
n=5 Participants
Patients will be enrolled within 24 hours of diagnosis of sepsis related to a necrotizing soft-tissue infections (NSTI). HAT will be initiated within 4 hours of enrollment (thus treatment with HAT can occur no later than 28 hours from diagnosis).
Per Dr. Marik's original study, HAT consists of:
1. 1.5 g vitamin C every 6 hours for 4 days or until ICU discharge
2. 50 mg hydrocortisone every 6 hours for 7 days or until ICU discharge (followed by a taper over 3 days)
3. 200 mg thiamine every 12 hours for 4 days or until ICU discharge In our study, due to the prolonged ICU course typical of most patients with NSTIs, it is not felt feasible to continue indefinitely "until ICU discharge." Thus, treatment will be continued for 4 to 7 days plus a 3 day taper (respectively) as above, with no plan for a longer duration of treatment.
HAT: hydrocortisone, ascorbic acid (vitamin C), and thiamine (vitamin B1); referred to as HAT
|
Control Arm
n=5 Participants
The control arm will receive the same standard ICU care for NSTI but will not receive HAT. They will receive a placebo consisting of normal saline, indistinguishable to the treatment team (blinded) but known to the pharmacy team (unblinded to treatment and placebo groups). This is so that if the treatment team elects to give stress dose steroids, they can be administered without breaking protocol (i.e. if the patient is getting HAT, it includes steroids, so if the treating team wanted to start hydrocortisone - because they didn't know if the patient was on HAT or placebo and felt steroids were indicated - the pharmacist could ensure the patient was on steroids one way or another without unblinding the providers).
Placebo: normal saline solution
|
|---|---|---|
|
Number of Wound Related Surgeries
|
4.0 Wound related surgeries
Interval 2.5 to 4.0
|
2.0 Wound related surgeries
Interval 1.5 to 2.5
|
SECONDARY outcome
Timeframe: Outcome is measured from date of admission to date of discharge or date of death, whichever comes first, approximately 7 to 10 days.This shows the number of participants with an open wound at time of hospital discharge.
Outcome measures
| Measure |
Treatment Arm
n=5 Participants
Patients will be enrolled within 24 hours of diagnosis of sepsis related to a necrotizing soft-tissue infections (NSTI). HAT will be initiated within 4 hours of enrollment (thus treatment with HAT can occur no later than 28 hours from diagnosis).
Per Dr. Marik's original study, HAT consists of:
1. 1.5 g vitamin C every 6 hours for 4 days or until ICU discharge
2. 50 mg hydrocortisone every 6 hours for 7 days or until ICU discharge (followed by a taper over 3 days)
3. 200 mg thiamine every 12 hours for 4 days or until ICU discharge In our study, due to the prolonged ICU course typical of most patients with NSTIs, it is not felt feasible to continue indefinitely "until ICU discharge." Thus, treatment will be continued for 4 to 7 days plus a 3 day taper (respectively) as above, with no plan for a longer duration of treatment.
HAT: hydrocortisone, ascorbic acid (vitamin C), and thiamine (vitamin B1); referred to as HAT
|
Control Arm
n=5 Participants
The control arm will receive the same standard ICU care for NSTI but will not receive HAT. They will receive a placebo consisting of normal saline, indistinguishable to the treatment team (blinded) but known to the pharmacy team (unblinded to treatment and placebo groups). This is so that if the treatment team elects to give stress dose steroids, they can be administered without breaking protocol (i.e. if the patient is getting HAT, it includes steroids, so if the treating team wanted to start hydrocortisone - because they didn't know if the patient was on HAT or placebo and felt steroids were indicated - the pharmacist could ensure the patient was on steroids one way or another without unblinding the providers).
Placebo: normal saline solution
|
|---|---|---|
|
Wound Status at Time of Hospital Discharge: Open
|
3 Participants
|
1 Participants
|
Adverse Events
Treatment Arm
Serious events: 0 serious events
Other events: 0 other events
Deaths: 3 deaths
Control Arm
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Dr. Thomas Resch
Department of Surgery, University of Kansas School of Medicine-Wichita
Phone: 316-268-5990
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place