Acetaminophen and Ascorbate in Sepsis: Targeted Therapy to Enhance Recovery

Browse trials for

• Sepsis 1,899
• Toxemia 936
• Respiratory Distress Syndrome 1,597
• Respiratory Distress Syndrome, Newborn 1,179
• Respiratory Insufficiency 1,650
• Acute Lung Injury 989

Keywords

• ARDS
• Acetaminophen
• Vitamin C
• Sepsis

Sepsis

1,899 studies on the registry are indexed under Sepsis; 462 are open to participants now.

This study's enrollment of 488 is above the median of 105 across 896 interventional studies indexed under Sepsis.

Lead sponsor

Massachusetts General Hospital is the lead sponsor of 2,536 studies on the registry; 446 are open to participants now.

Of its 214 completed or terminated interventional studies of FDA-regulated products, 161 (75%) have results posted.

Study arms

• Active comparator
  IV Acetaminophen-Active

  Patients randomized to the Acetaminophen arm will receive Acetaminophen at the dose of 1 gram (or 15 mg/kg if actual body weight \< 50kg) in 100 ml 5% dextrose in water every 6 hours intravenously for 5 days (20 doses).

  Drug: Intravenous Acetaminophen (room temperature)

• Active comparator
  IV Vitamin C-Active

  Patients randomized to the Vitamin C arm will receive Vitamin C at the dose of 50 mg/kg in 100 ml 5% dextrose in water every 6 hours intravenously for 5 days (20 doses). Note: This arm is now closed.

  Drug: Intravenous Vitamin C (refrigerated)

• Placebo comparator
  Acetaminophen-Placebo

  Patients randomized to placebo will receive an identical-appearing intravenous infusion of 100 ml of 5% dextrose in water every 6 hours for 5 days (20 doses).

  Drug: 5% Dextrose (room temperature)

• Placebo comparator
  Vitamin C-Placebo

  Patients randomized to placebo will receive an identical-appearing intravenous infusion of 100 ml of 5% dextrose in water every 6 hours for 5 days (20 doses). Note: This arm is now closed.

  Drug: 5% Dextrose refrigerated

Interventions

• DrugIntravenous Acetaminophen (room temperature)

  Acetaminophen given intravenously at the dose of 1 gram (or 15 mg/kg if patient weighs \< 50 kg) every six hours for 5 days (20 doses)

• DrugIntravenous Vitamin C (refrigerated)

  Vitamin C given intravenously at the dose of 50 mg/kg every six hours for 5 days (20 doses)

  Also known as: Ascor

• Drug5% Dextrose (room temperature)

  Placebo (identical appearing room temperature 5% dextrose solution) infused every six hours for 5 days (20 doses)

• Drug5% Dextrose refrigerated

  Placebo (identical appearing refrigerated 5% dextrose solution) infused every six hours for 5 days (20 doses)

Primary outcomes

1. Days Alive and Free of Organ Support to Day 28

   Defined as the days alive and free of organ support (dialysis, assisted ventilation, and vasopressors) to day 28. Participants will need to be free of all three components (assisted ventilation, vasopressors, new renal replacement therapy) to qualify for a day alive and free from organ failures. Patients on chronic dialysis will not be scored for the new renal failure free component of this outcome.

   Time frame: 28 days after randomization

2. 28-day All Cause Mortality

   Vital status at study day 28 regardless of location or cause of death. Patients discharged from the study hospital are followed to day 29 to determine this endpoint.

   Time frame: 28 days after randomization

3. Days Free of Assisted Ventilation to Day 28

   The number of days alive and without assisted ventilation (midnight to midnight) in the overall cohort. No penalty for death.

   Time frame: 28 days after randomization

4. Days Free of Renal Replacement Therapy to Day 28 in Overall Cohort

   The number of days alive and without renal replacement (RRT) in the overall cohort. If a participant was not on RRT at randomization, received RRT every other day, and stopped RRT before day 28, the number of renal replacement free days is the sum of the days free of RRT prior to dialysis starting and the number of days after dialysis stopped (begins with the first day, midnight to midnight, the participant was free of RRT). No penalty for death.

   Time frame: 28 days after randomization

5. Days Free of Vasopressors to Day 28 in Overall Cohort

   Days free of vasopressors to day 28 are defined as the number of calendar days (midnight to midnight) between randomization and 28 days later that the patient is alive and did not receive vasopressor therapy.

   Time frame: 28 days after randomization

Secondary outcomes

1. Ventilator-free Days (VFD)

   VFDs depend on both duration of ventilation and mortality through study day 28. In participants who survive 28 days, VFD is defined as 28 minus days of invasive or noninvasive ventilation to day 28. Duration of ventilation is counted from the first study day of assisted breathing through the last day of assisted breathing provided the last day is prior to day 28. Isolated periods of ventilation briefer than 24 hours for surgical procedures and ventilation solely for sleep disordered breathing do not count towards duration of ventilation. In participants who never require assisted breathing, duration of ventilation is zero. Participants who do not survive 28 days will be assigned zero VF

   Time frame: 28 days after randomization

2. Vasopressor-free Days

   Vasopressor free days to day 28 are defined as the number of calendar days between randomization and 28 days later that the patient is alive and without the use of vasopressor therapy. Patients who die prior to day 28 and those who receive vasopressor therapy for the entire first 28 days are assigned zero vasopressor free days.

   Time frame: 28 days after randomization

3. Renal Replacement-free Days

   Renal replacement free days to day 28 are defined as the number of calendar days between randomization and 28 days later that the patient is alive and without renal replacement therapy. We also follow the "last off" method. Patients who died prior to day 28 and those who receive renal replacement therapy for the entire first 28 days are assigned zero renal replacement free days.

   Time frame: 28 days after randomization

4. 28 Day Hospital Mortality

   All deaths occuring in the study hospital until study day 28.

   Time frame: 28 days after randomization

5. ICU Free Days

   The number of days spent alive out of the ICU to day 28.

   Time frame: 28 days after randomization

6. Hospital Free Days to Discharge Home

   Defined as 28 days minus the number of days from randomization to discharge home. If a patient has not been discharged home prior to study day 28 or dies prior to day 28, hospital free days will be zero. Patients transferred to another hospital or other health care facility will be followed to day 28 to assess this endpoint.

   Time frame: Up to day 28

7. Number of Subjects With Initiation of Assisted Ventilation

   Any patient who received assisted ventilation during the study hospitalization to study day 28 days meets this endpoint.

   Time frame: Up to day 28

8. Number of Subjects With Initiation of Renal Replacement Therapy

   Patients who receive (new) renal replacement therapy through day 28 will meet this endpoint. Patients with chronic renal replacement therapy initiated prior to the current sepsis illness will not be eligible to meet this endpoint.

   Time frame: Up to day 28

9. Change in Organ-specific Sepsis-related Organ Failure Assessment (SOFA) Scores Between Enrollment and Study Day 7

   SOFA score calculated upon enrollment and at day 7 using clinically available data. If a value is not available at baseline, it will be assumed to be normal. Missing values at day 7 assessment were carried forward to the closest known value. GSC was omitted for patients intubated/heavily sedated at either 0 or day 7 when calculating the change in score. Renal dysfunction component was omitted for patients RRT prior to presentation.Higher SOFA score=worse outcome.ASTER clinically significant organ failure:SOFA score 2 or more points higher than baseline.Total score range: 0(min)-24(max) Score:Coag(platelets x10³/µL:0:\>150;1:\</=150; 2:\</=100; 3:\</=50; 4:\</=20. Liver(bilirubin, mg/dL): 0:\<1.2; 1: 1.2-1.9; 3: 2.0-5.9; 3: 6.0-11.9; 4:\>11.9. Cardio(hypotension): 0:none; 1: MAP \<70 mmHg; 2: Dop\</=5 or dob (any dose); 3:dop\>5, epi\</=0.1, or norepi\</=0.1; 4: Dop\>15, epi\>0.1, or norepi\>0.1. Renal(Cr, mg/dL or urine output,ml/d): 0:\<1.2; 1: 1.2-1.9; 3: 2.0-3.4; 3: 3.5-4.9 or \<500; 4:\>4.9 or\<200.

   Time frame: Day 0-Day 7

10. Renal Calculi to Day 90

    Renal calculi diagnosed between randomization and study day 90 in patients in the Vitamin C-Active/Vitamin C-Placebo group.

    Time frame: Up to day 90

11. 90-day All-cause Mortality

    Vital status of the patient at day 90 will be determined using any of the following methods: medical record review, phone calls to patient, proxy or healthcare facility, review of obituaries, or information from the Centers for Disease Control and Prevention's National Death Index (NDI).

    Time frame: 90 days after randomization

12. 90-day Hospital Mortality

    Vital status prior to discharge home before day 90.

    Time frame: 90 days after randomization

13. Number of Subjects Who Developed ARDS Within 7 Days of Randomization

    The presence of ARDS for each day is defined as receiving assisted ventilation with P/F \<300 or imputed P/F \<300, FiO2 ≥40%, and PEEP ≥5 cm H2O and not fully explained by CHF or fluid overload. ARDS imaging criteria are met if clinically available chest images (CT or CXR) are consistent with ARDS (bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules).

    Time frame: Up to day 7

14. Change in Serum Creatinine Concentration

    We will measure the change in serum creatinine from enrollment to discharge, death, initiation of dialysis or 28 days, whichever occurs first

    Time frame: Up to day 28

15. Number of Subjects With Major Adverse Kidney Events at 28 Days (MAKE28)

    Defined as persistent increase in serum creatinine by 200% from baseline, need for new renal replacement therapy, or death

    Time frame: 28 days after randomization

16. ICU Days to Day 28

    ICU free days to day 28 are defined as the number of days spent alive and out of the ICU to day 28.

    Time frame: To day 28

Baseline characteristics

17 further baseline measures are reported on the registry.

Related links

• Website for the PETAL Network ↗

Study documents

• Study protocol · Jun 8, 2021
• Study protocol · Apr 25, 2023
• Statistical analysis plan · Sep 21, 2023
• Informed consent form · Jul 14, 2021
• Informed consent form · Jul 27, 2022
• Informed consent form · Jul 7, 2022

Documents are hosted by the registry — open the source record to download them.