Acute Hypoxemic Respiratory Failure
Conditions
Brief summary
Prospective, Randomized, Double-Blind, Placebo-Controlled Phase II Trial of Intravenous L-Citrulline (Turnobi) to Delay and Potentially Prevent the Need for Invasive Mechanical Ventilation for Acute Hypoxemic Respiratory Failure in Patients with COVID-19 (SARS-CoV2) Illness. To evaluate safety and efficacy of a bolus loading dose and continuous intravenous infusion of L-Citrulline compared to placebo in patients hospitalized with COVID-19 infection (SARS-CoV-2).
Detailed description
Intravenous L-citrulline (Turnobi) administration will safely restore the homeostasis of nitric oxide synthase by increasing both plasma citrulline and arginine levels. Investigators also reason that restoration of citrulline/arginine balance through citrulline administration will safely re-establish homeostasis of NOS, lower oxidative stress, and reduce inflammation, thereby delaying and potentially preventing the need for invasive mechanical ventilation in participants hospitalized with COVID-19 infection (SARS-CoV-2). The body lives in a delicate balance of homeostasis. The urea/NO cycle plays a critical role in maintaining redox homeostasis and as such, also plays a role in regulating inflammation. The biochemical relationships are complex and depend on inter-organ transfer, membrane transport, and intracellular compartmentation. However, data above demonstrate that citrulline, arginine, and NO are critical in maintaining this homeostasis through their regulation of NOS. Inflammation, especially from infection, results in decreased activity of CPS1 and increased activity of arginase, which decreases levels of both citrulline and arginine. These decreased levels result in dysregulated and uncoupled NOS, which drives both overexuberant NO production and formation of ROS. Both the NO production and ROS further exacerbate the inflammatory cascade, resulting in other organ dysfunctions, including acute lung injury. Both inflammation and oxidative stress have been shown to be driving forces for the development of ALI and regulated NOS function is vital to reducing both. Both plasma citrulline and arginine are deficient in sepsis and levels are inversely associated with development of ALI. Furthermore, citrulline replacement safely increases plasma levels of both citrulline and arginine in healthy volunteers, BMT patients, adults with sepsis, children with sickle cell disease, and children after congenital heart surgery. It seems highly likely that citrulline therapy in the setting of COVID-19 (SARS-CoV2) induced acute hypoxemic respiratory illness will safely increase citrulline and arginine levels and help re-establish NOS homeostasis, resulting in NO production in compartments that are more homeostatically appropriate so as to reduce pulmonary vascular resistance and enhance coupling of NOS to minimize superoxide production thus reducing free radical mediated ALI.
Interventions
DRUGL-Citrulline
L-Citrulline (Turnobi) for Injection. Patients will receive an initial bolus of 20 mg/kg (maximum 1500 mg), followed by study infusion of 9 mg/kg per hour (maximum 700mg) for up to 10 days.
DRUGPlacebo
Patients randomized to placebo will receive equal volume bolus and study infusion of 5% dextrose water for a maximum of 10 days.
Sponsors
Asklepion Pharmaceuticals, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double Blind Clinical Trial
Intervention model description
Placebo controlled and Active Drug
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-65 years. 2. Clinical evidence of COVID-19 (SARS-CoV2) infection, defined as a positive COVID-19 laboratory test plus evidence of an acute hypoxemic respiratory illness requiring oxygen. 3. Admitted and transferred to floor without intubation.
Exclusion criteria
1. No consent/inability to obtain consent 2. Patient, surrogate, or physician not committed to full support 3. Malignant or other irreversible condition and estimated 28-day mortality ≥ 50% 4. Moribund patient not expected to survive 48 hours (as defined by primary medical team) from start of study infusion 5. End-stage Liver Disease as defined by Child-Pugh Score \> 9 6. Currently enrolled in, or participated in another study of an investigational compound within the last 30 days 7. Pregnant female, or female who is breast feeding 8. Allergy to L-citrulline or arginine or any citrulline- or arginine-containing product 9. Patient not otherwise suitable for the study in the opinion of any of the investigators 10. Requirement for intubation and invasive mechanical ventilation before study enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Non-invasive/Invasive Mechanical Ventilation | From the start of infusion to Day 60 Follow-up | Time in hours from the initiation of the treatment until mechanical ventilation is required, whether non-invasive (e.g., high flow nasal cannula, bilevel positive airway pressure, oxygen therapy) or invasive (i.e., requiring intubation). |
| Time to Non-invasive Mechanical Ventilation | From the start of infusion to Day 60 Follow-up | Time in hours from the initiation of the treatment until non-invasive mechanical ventilation is required (e.g., high flow nasal cannula, bilevel positive airway pressure, oxygen therapy) . |
| Time to Invasive Mechanical Ventilation | From the start of infusion to Day 60 Follow-up | Time in hours from the initiation of the treatment until intubation for invasive mechanical ventilation is required. |
| Systolic Blood Pressure | Day 1 | Systolic blood pressure measured in mmHg |
| Diastolic Blood Pressure | Day 1 | Diastolic blood pressure measured in mmHg |
| Mean Arterial Pressure | Day 1 | Mean arterial pressure measured in mmHg |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Hospitalisation | From admission to hospital until discharge or death | Length of hospital stay (days) |
| Blood Levels of Arginine | Plasma levels of arginine at 0, 2 and 12 hours, and 2, 4, 6, 8, 10 days after initiation of treatment | Plasma levels of arginine |
| Overall Duration of Mechanical Ventilation | From the start of infusion to Day 60 Follow-up | Total time on any mechanical ventilation, invasive mechanical ventilation, non-invasive mechanical ventilation and nasal cannula |
| Number of Patients Requiring Intubation | From the start of infusion to Day 60 Follow-up | Percentage of patients requiring any mechanical ventilation, invasive mechanical ventilation and non-invasive mechanical ventilation. |
| Blood Levels of Citrulline | Plasma levels of citrulline at 0, 2 and 12 hours, and 2, 4, 6, 8, 10 days after initiation of treatment | Plasma levels of citrulline |
| Evaluate the Effect of Intravenous L-Citrulline Compared to Placebo as Measured by the Total Length of All Mechanical Ventilation | Day 1 through Day 60 Follow Up | Total length of time of any mechanical ventilation |
| Evaluate the Effect of IV L-Citrulline to Placebo for Hospital All Cause Mortality | Day 1 through day 12 | To evaluate the effect of intravenous L-Citrulline compared to placebo on Hospital all-cause mortality |
| Percentage of Patients Admitted to Intensive Care | Day 1 through Day 12 (DC) | — |
| Duration of Intensive Care Unit (ICU) Stay | From admission to ICU until discharge or death | Length of ICU stay (days) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IV L-Citrulline (Turnobi) Arm Patients randomized to citrulline will receive an initial intravenous bolus of 20 mg/kg (to a maximum of 1500 mg) L-citrulline over 10 minutes. The study solution will be prepared as a 5% isotonic solution (50 mg/mL) in 5% dextrose water. Immediately after the initial bolus, a continuous intravenous infusion of L-citrulline at 9 mg/kg (max 700 mg) per hour will be administered through a dedicated intravenous line or port of a multi-lumen catheter.
L-Citrulline: L-Citrulline (Turnobi) for Injection. Patients will receive an initial bolus of 20 mg/kg (maximum 1500 mg), followed by study infusion of 9 mg/kg per hour (maximum 700mg) for up to 10 days. | 33 |
| Placebo Arm Patients randomized to placebo arm will receive an infusion of 5% dextrose water matched for volume and color to the citrulline infusion. The placebo infusion will consist of an initial iv bolus (up to 30 mL) over 10 minutes followed by a continuous infusion of 5% dextrose water (about 15 mL/hr). The initial bolus and subsequent infusion will be administered through a dedicated intravenous line or port of a multi-lumen catheter.
Placebo: Patients randomized to placebo will receive equal volume bolus and study infusion of 5% dextrose water for a maximum of 10 days. | 32 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Death | 2 | 5 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Sponsor Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | IV L-Citrulline (Turnobi) Arm | Placebo Arm | Total |
|---|---|---|---|
| Age, Continuous | 50.30 years STANDARD_DEVIATION 11.04 | 51.13 years STANDARD_DEVIATION 10.34 | 50.71 years STANDARD_DEVIATION 10.63 |
| Age, Customized 18-49 years | 13 Participants | 12 Participants | 25 Participants |
| Age, Customized 50-65 years | 20 Participants | 20 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 26 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants | 17 Participants | 35 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) White | 12 Participants | 12 Participants | 24 Participants |
| Sex: Female, Male Female | 16 Participants | 9 Participants | 25 Participants |
| Sex: Female, Male Male | 17 Participants | 23 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 33 | 5 / 32 |
| other Total, other adverse events | 11 / 33 | 11 / 32 |
| serious Total, serious adverse events | 6 / 33 | 10 / 32 |
Outcome results
Primary
Diastolic Blood Pressure
Diastolic blood pressure measured in mmHg
Time frame: Day 1
Population: Patients in the safety population with measurement(s) of diastolic blood pressure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV L-Citrulline (Turnobi) Arm | Diastolic Blood Pressure | 73.58 Millimeters of mercury | Standard Deviation 10.06 |
| Placebo Arm | Diastolic Blood Pressure | 79.74 Millimeters of mercury | Standard Deviation 13.13 |
Primary
Mean Arterial Pressure
Mean arterial pressure measured in mmHg
Time frame: Day 1
Population: Patients in the safety population with measurement(s) of mean arterial blood pressure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV L-Citrulline (Turnobi) Arm | Mean Arterial Pressure | 87.58 Millimeters of mercury | Standard Deviation 10.03 |
| Placebo Arm | Mean Arterial Pressure | 94.30 Millimeters of mercury | Standard Deviation 13.49 |
Primary
Systolic Blood Pressure
Systolic blood pressure measured in mmHg
Time frame: Day 1
Population: Patients in the safety population with measurement(s) of systolic blood pressure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV L-Citrulline (Turnobi) Arm | Systolic Blood Pressure | 118.63 Millimeters of mercury | Standard Deviation 14.69 |
| Placebo Arm | Systolic Blood Pressure | 130.19 Millimeters of mercury | Standard Deviation 15.71 |
Primary
Time to Invasive Mechanical Ventilation
Time in hours from the initiation of the treatment until intubation for invasive mechanical ventilation is required.
Time frame: From the start of infusion to Day 60 Follow-up
Population: Patients in the Intent-to-treat population requiring intubation for invasive mechanical ventilation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV L-Citrulline (Turnobi) Arm | Time to Invasive Mechanical Ventilation | 290.01 Hours | Standard Deviation 254.31 |
| Placebo Arm | Time to Invasive Mechanical Ventilation | 148.07 Hours | Standard Deviation 108.08 |
p-value: 0.28595% CI: [0.13, 1.83]Log Rank
p-value: 0.47195% CI: [0.15, 2.41]Regression, Logistic
Primary
Time to Non-invasive/Invasive Mechanical Ventilation
Time in hours from the initiation of the treatment until mechanical ventilation is required, whether non-invasive (e.g., high flow nasal cannula, bilevel positive airway pressure, oxygen therapy) or invasive (i.e., requiring intubation).
Time frame: From the start of infusion to Day 60 Follow-up
Population: Patients in the Intent-to-treat population that required invasive or non-invasive ventilation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV L-Citrulline (Turnobi) Arm | Time to Non-invasive/Invasive Mechanical Ventilation | 96.65 Hours | Standard Deviation 143.73 |
| Placebo Arm | Time to Non-invasive/Invasive Mechanical Ventilation | 70.49 Hours | Standard Deviation 62.44 |
p-value: 0.78295% CI: [0.45, 2.86]Log Rank
p-value: 0.66895% CI: [0.46, 3.4]Regression, Logistic
Primary
Time to Non-invasive Mechanical Ventilation
Time in hours from the initiation of the treatment until non-invasive mechanical ventilation is required (e.g., high flow nasal cannula, bilevel positive airway pressure, oxygen therapy) .
Time frame: From the start of infusion to Day 60 Follow-up
Population: Patients in the Intent-to-treat population requiring non-invasive mechanical ventilation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV L-Citrulline (Turnobi) Arm | Time to Non-invasive Mechanical Ventilation | 66.17 Hours | Standard Deviation 105.4 |
| Placebo Arm | Time to Non-invasive Mechanical Ventilation | 105.70 Hours | Standard Deviation 108.9 |
p-value: 0.3695% CI: [0.59, 4.22]Log Rank
Secondary
Blood Levels of Arginine
Plasma levels of arginine
Time frame: Plasma levels of arginine at 0, 2 and 12 hours, and 2, 4, 6, 8, 10 days after initiation of treatment
Population: Patients with at least 1 measurement of plasma arginine
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IV L-Citrulline (Turnobi) Arm | Blood Levels of Arginine | Hour 12 | 128.11 µmol/L | Standard Deviation 41.3 |
| IV L-Citrulline (Turnobi) Arm | Blood Levels of Arginine | Day 8 | 167.64 µmol/L | Standard Deviation 82.5 |
| IV L-Citrulline (Turnobi) Arm | Blood Levels of Arginine | Day 10 | 160.02 µmol/L | Standard Deviation 83.39 |
| IV L-Citrulline (Turnobi) Arm | Blood Levels of Arginine | Day 4 | 152.00 µmol/L | Standard Deviation 66.7 |
| IV L-Citrulline (Turnobi) Arm | Blood Levels of Arginine | Day 6 | 169.33 µmol/L | Standard Deviation 113.62 |
| IV L-Citrulline (Turnobi) Arm | Blood Levels of Arginine | Day 2 | 142.02 µmol/L | Standard Deviation 54.51 |
| IV L-Citrulline (Turnobi) Arm | Blood Levels of Arginine | Hour 0 | 67.6 µmol/L | Standard Deviation 28.27 |
| IV L-Citrulline (Turnobi) Arm | Blood Levels of Arginine | Hour 2 | 92.57 µmol/L | Standard Deviation 30.84 |
| Placebo Arm | Blood Levels of Arginine | Hour 0 | 67.88 µmol/L | Standard Deviation 29.51 |
| Placebo Arm | Blood Levels of Arginine | Day 6 | 70.78 µmol/L | Standard Deviation 19.46 |
| Placebo Arm | Blood Levels of Arginine | Hour 12 | 75.7 µmol/L | Standard Deviation 24.54 |
| Placebo Arm | Blood Levels of Arginine | Day 8 | 81.79 µmol/L | Standard Deviation 32.28 |
| Placebo Arm | Blood Levels of Arginine | Day 2 | 82.19 µmol/L | Standard Deviation 26.33 |
| Placebo Arm | Blood Levels of Arginine | Day 10 | 83.9 µmol/L | Standard Deviation 37.36 |
| Placebo Arm | Blood Levels of Arginine | Hour 2 | 71.51 µmol/L | Standard Deviation 29.15 |
| Placebo Arm | Blood Levels of Arginine | Day 4 | 79.66 µmol/L | Standard Deviation 22.84 |
Secondary
Blood Levels of Citrulline
Plasma levels of citrulline
Time frame: Plasma levels of citrulline at 0, 2 and 12 hours, and 2, 4, 6, 8, 10 days after initiation of treatment
Population: All patients with at least 1 plasma citrulline measurement
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IV L-Citrulline (Turnobi) Arm | Blood Levels of Citrulline | Hour 0 | 24.64 µmol/L | Standard Deviation 25.91 |
| IV L-Citrulline (Turnobi) Arm | Blood Levels of Citrulline | Hour 2 | 1094.41 µmol/L | Standard Deviation 2463.97 |
| IV L-Citrulline (Turnobi) Arm | Blood Levels of Citrulline | Hour 12 | 997.61 µmol/L | Standard Deviation 2133.07 |
| IV L-Citrulline (Turnobi) Arm | Blood Levels of Citrulline | Day 2 | 278.2 µmol/L | Standard Deviation 353.32 |
| IV L-Citrulline (Turnobi) Arm | Blood Levels of Citrulline | Day 4 | 626.33 µmol/L | Standard Deviation 1562.95 |
| IV L-Citrulline (Turnobi) Arm | Blood Levels of Citrulline | Day 6 | 185.14 µmol/L | Standard Deviation 68.63 |
| IV L-Citrulline (Turnobi) Arm | Blood Levels of Citrulline | Day 8 | 192.72 µmol/L | Standard Deviation 127.72 |
| IV L-Citrulline (Turnobi) Arm | Blood Levels of Citrulline | Day 10 | 206.26 µmol/L | Standard Deviation 135.94 |
| Placebo Arm | Blood Levels of Citrulline | Day 10 | 24.56 µmol/L | Standard Deviation 11.46 |
| Placebo Arm | Blood Levels of Citrulline | Hour 0 | 18.08 µmol/L | Standard Deviation 13.7 |
| Placebo Arm | Blood Levels of Citrulline | Day 4 | 20.53 µmol/L | Standard Deviation 15.84 |
| Placebo Arm | Blood Levels of Citrulline | Hour 2 | 18.39 µmol/L | Standard Deviation 14.08 |
| Placebo Arm | Blood Levels of Citrulline | Day 8 | 24.84 µmol/L | Standard Deviation 9.64 |
| Placebo Arm | Blood Levels of Citrulline | Hour 12 | 21.84 µmol/L | Standard Deviation 16.14 |
| Placebo Arm | Blood Levels of Citrulline | Day 6 | 20.96 µmol/L | Standard Deviation 10.16 |
| Placebo Arm | Blood Levels of Citrulline | Day 2 | 24.68 µmol/L | Standard Deviation 27.57 |
Secondary
Duration of Hospitalisation
Length of hospital stay (days)
Time frame: From admission to hospital until discharge or death
Population: Intent-to-treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV L-Citrulline (Turnobi) Arm | Duration of Hospitalisation | 10.61 Days | Standard Deviation 12.74 |
| Placebo Arm | Duration of Hospitalisation | 11.88 Days | Standard Deviation 14.29 |
p-value: 0.83495% CI: [0.52, 2.25]Negative binomial analysis
Secondary
Duration of Intensive Care Unit (ICU) Stay
Length of ICU stay (days)
Time frame: From admission to ICU until discharge or death
Population: Intent-to-treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV L-Citrulline (Turnobi) Arm | Duration of Intensive Care Unit (ICU) Stay | 14.83 Days | Standard Deviation 12.29 |
| Placebo Arm | Duration of Intensive Care Unit (ICU) Stay | 17.31 Days | Standard Deviation 18.87 |
p-value: 0.70695% CI: [0.43, 3.44]Zero-inflated negative binomial analyses
p-value: 0.78895% CI: [0.49, 2.56]Zero-inflated negative binomial analyses
Secondary
Evaluate the Effect of Intravenous L-Citrulline Compared to Placebo as Measured by the Total Length of All Mechanical Ventilation
Total length of time of any mechanical ventilation
Time frame: Day 1 through Day 60 Follow Up
Population: Patients in the Intent-to-treat population requiring mechanical ventilation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV L-Citrulline (Turnobi) Arm | Evaluate the Effect of Intravenous L-Citrulline Compared to Placebo as Measured by the Total Length of All Mechanical Ventilation | 270.91 Hours | Standard Deviation 304.03 |
| Placebo Arm | Evaluate the Effect of Intravenous L-Citrulline Compared to Placebo as Measured by the Total Length of All Mechanical Ventilation | 451.87 Hours | Standard Deviation 503.68 |
p-value: 0.66895% CI: [0.3, 2.2]Zero-inflated negative binomial analyses
p-value: 0.43795% CI: [0.23, 1.9]Zero-inflated negative binomial analyses
Secondary
Evaluate the Effect of IV L-Citrulline to Placebo for Hospital All Cause Mortality
To evaluate the effect of intravenous L-Citrulline compared to placebo on Hospital all-cause mortality
Time frame: Day 1 through day 12
Population: Intent-to-treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV L-Citrulline (Turnobi) Arm | Evaluate the Effect of IV L-Citrulline to Placebo for Hospital All Cause Mortality | 2 Participants |
| Placebo Arm | Evaluate the Effect of IV L-Citrulline to Placebo for Hospital All Cause Mortality | 5 Participants |
p-value: 0.23295% CI: [0.06, 1.97]Regression, Logistic
Secondary
Number of Patients Requiring Intubation
Percentage of patients requiring any mechanical ventilation, invasive mechanical ventilation and non-invasive mechanical ventilation.
Time frame: From the start of infusion to Day 60 Follow-up
Population: Intent-to-treat
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV L-Citrulline (Turnobi) Arm | Number of Patients Requiring Intubation | Non-invasive/invasive mechanical ventilation | 14 Participants |
| IV L-Citrulline (Turnobi) Arm | Number of Patients Requiring Intubation | Non-invasive mechanical ventilation | 12 Participants |
| IV L-Citrulline (Turnobi) Arm | Number of Patients Requiring Intubation | Invasive mechanical ventilation | 4 Participants |
| Placebo Arm | Number of Patients Requiring Intubation | Non-invasive/invasive mechanical ventilation | 12 Participants |
| Placebo Arm | Number of Patients Requiring Intubation | Non-invasive mechanical ventilation | 10 Participants |
| Placebo Arm | Number of Patients Requiring Intubation | Invasive mechanical ventilation | 6 Participants |
Secondary
Overall Duration of Mechanical Ventilation
Total time on any mechanical ventilation, invasive mechanical ventilation, non-invasive mechanical ventilation and nasal cannula
Time frame: From the start of infusion to Day 60 Follow-up
Population: Intent-to-treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IV L-Citrulline (Turnobi) Arm | Overall Duration of Mechanical Ventilation | Total time on mechanical ventilation | 239.31 Hours | Standard Deviation 243.08 |
| IV L-Citrulline (Turnobi) Arm | Overall Duration of Mechanical Ventilation | Total time of non-invasive mechanical ventilation | 224.64 Hours | Standard Deviation 254.22 |
| IV L-Citrulline (Turnobi) Arm | Overall Duration of Mechanical Ventilation | Total time of invasive mechanical ventilation | 274.27 Hours | Standard Deviation 158.86 |
| IV L-Citrulline (Turnobi) Arm | Overall Duration of Mechanical Ventilation | Total time on Nasal Cannula | 239.31 Hours | Standard Deviation 243.08 |
| Placebo Arm | Overall Duration of Mechanical Ventilation | Total time on Nasal Cannula | 222.08 Hours | Standard Deviation 370.9 |
| Placebo Arm | Overall Duration of Mechanical Ventilation | Total time on mechanical ventilation | 222.08 Hours | Standard Deviation 370.9 |
| Placebo Arm | Overall Duration of Mechanical Ventilation | Total time of invasive mechanical ventilation | 538.28 Hours | Standard Deviation 469.21 |
| Placebo Arm | Overall Duration of Mechanical Ventilation | Total time of non-invasive mechanical ventilation | 219.27 Hours | Standard Deviation 309.4 |
Secondary
Percentage of Patients Admitted to Intensive Care
Time frame: Day 1 through Day 12 (DC)
Population: Intent-to-treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV L-Citrulline (Turnobi) Arm | Percentage of Patients Admitted to Intensive Care | 12 Participants |
| Placebo Arm | Percentage of Patients Admitted to Intensive Care | 13 Participants |
p-value: 0.72995% CI: [0.31, 2.28]Regression, Logistic