COVID-19 Infection
Conditions
Brief summary
We are conducting an investigator-initiated, single center, blinded, placebo-controlled, randomized clinical trial evaluating magnesium citrate combined with a probiotic for the treatment of adults hospitalized with COVID-19.
Detailed description
We are conducting an investigator-initiated, single center, blinded, placebo-controlled, randomized clinical trial evaluating magnesium citrate combined with a probiotic for the treatment of adults hospitalized with COVID-19. Patients, treating clinicians, and study personnel will all be blinded to study group assignment. This research study is being done to determine if taking oral magnesium citrate and a probiotic will improve the outcome of adults hospitalized with COVID-19. In this study, half of the participants will receive magnesium citrate plus a probiotic and half will receive a placebo randomized 1:1. You will be placed in one of these 2 groups randomly, like the flip of a coin. The investigational arm will receive one 10 oz. bottle of magnesium citrate to drink once and 2 oral probiotic capsules to be taken twice a day for 6 days. We will also collect a blood sample on Day 1 and Day 7 for CD4+ and CD8+ evaluation and will be collecting data on each participants COVID-19 infection progression during hospitalization. Assessments for this study will be done on day 7 and day 29 if the participant is still hospitalized at those time points. If they have been discharged from the hospital before these assessments, we will do these by phone. Each participant will also be contacted at 3 months to assess how they are doing. There will be no compensation for taking part in this study.
Interventions
DRUGMagnesium Citrate plus probiotic
296 ml magnesium citrate
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Blinded, single-center, placebo-controlled randomized clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years 2. Currently hospitalized or in an emergency department with anticipated hospitalization. 3. Symptoms of acute respiratory infection, defined as one or more of the following: 1. Cough 2. Fever (\> 37.5° C / 99.5° F) 3. Shortness of breath (operationalized as any of the following: subjective shortness of breath reported by patient or surrogate; tachypnea with respiratory rate ≥22 /minute; hypoxemia, defined as SpO2 \<92% on room air, new receipt of supplemental oxygen to maintain SpO2 ≥92%, or increased supplemental oxygen to maintain SpO2 ≥92% for a patient on chronic oxygen therapy). 4. Sore throat 5. Anosmia 4. Laboratory-confirmed SARS (Severe acute respiratory syndrome-Coronavirus 2 (SARS CoV-2) infection within 10 days prior to randomization 5. Ability to manage own stool care
Exclusion criteria
1. Prisoner 2. Pregnancy 3. Breast feeding 4. Current infectious or noninfectious diarrheal illness 5. Unable to randomize within 21 days after onset of acute respiratory infection symptoms 6. Unable to randomize after hospital arrival 7. Colonic obstruction 8. Unresolved hypovolemia 9. CrCl \<30ml/min 10. Hypermagnesemia 11. Diagnosis of Long QT syndrome 12. Known allergy to magnesium citrate or probiotic 13. Unresolved electrolyte imbalance such as hypokalemia or hypocalcemia. The patient can be enrolled if electrolytes are corrected and sustained. 14. Receipt of \>1 dose of magnesium citrate or any other colonic cleanser in the 7 days prior to enrollment 15. Inability to receive enteral medications 16. Refusal or inability to be contacted on Day 15 for clinical outcome assessment if discharged prior to Day 15 17. Concurrent medical illness that interferes with clinical assessment Previous enrollment in this trial 18. The treating clinical team does not believe equipoise exists regarding the use of magnesium citrate plus a probiotic for the treatment of this patient. 19. Participating in any other COVID-19 therapeutic trial 20. Allergic to soy. 21. Lactose intolerant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| COVID Ordinal Outcome Scale | Baseline through Day 7 after completion of therapy | Outcome measured clinical status of the participant defined by the COVID Ordinal Outcome Scale on Day 7: 0 = Uninfected, no viral RNA detected 1. = Asymptomatic, viral RNA detected 2. = Symptomatic, independent 3. = Symptomatic, assistance needed 4. = Hospitalized, no oxygen needed 5. = Hospitalized, oxygen by mask or nasal prongs 6. = Hospitalized, oxygen by NIV or high flow 7. = Intubation and mechanical ventilation, pO2/FiO2 ≥150 or SpO2/FiO2 ≥200 8. = Mechanical ventilation, pO2/FiO2 \<150 (SpO2/FiO2 \<200) or vasopressors 9. = Mechanical ventilation, pO2/FiO2 \<150 and vasopressors, dialysis or ECMO 10. = Dead |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Oxygen Requirements From Baseline to Day 7 by Treatment Group | baseline and 7 days | Measured by liters of oxygen per minute to maintain saturation above 90% |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Magnesium Citrate Plus a Probiotic Arm: Participants assigned to the magnesium citrate plus a probiotic arm will receive 1 bottle of magnesium citrate 296 mL PO once to be taken within a 4-hour period, (about 10 oz.). Because magnesium citrate remains within the intestinal lumen, a second bottle can be provided if there is limited bowel movement. Patients will be asked to take 2 capsules of probiotics twice daily for six days or until discharge, whichever is earlier.
Magnesium Citrate plus probiotic: 296 ml magnesium citrate | 8 |
| Placebo Participants randomized to the placebo arm will receive matching placebo 296 mL PO once to be taken within a 4-hour period, (about 10 oz.) and 2 cellulose capsules twice daily for six days or until discharge, whichever is earlier. The placebo will be flavored to match the taste of the interventional arm.
Magnesium Citrate plus probiotic: 296 ml magnesium citrate | 10 |
| Total | 18 |
Baseline characteristics
| Characteristic | Magnesium Citrate Plus a Probiotic Arm: | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 9 Participants | 16 Participants |
| Age, Continuous | 67.5 years | 62.0 years | 66.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 8 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 6 Participants | 13 Participants |
| Region of Enrollment United States | 8 participants | 10 participants | 18 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 5 Participants | 7 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 10 |
| other Total, other adverse events | 0 / 8 | 0 / 10 |
| serious Total, serious adverse events | 0 / 8 | 0 / 10 |
Outcome results
Primary
COVID Ordinal Outcome Scale
Outcome measured clinical status of the participant defined by the COVID Ordinal Outcome Scale on Day 7: 0 = Uninfected, no viral RNA detected 1. = Asymptomatic, viral RNA detected 2. = Symptomatic, independent 3. = Symptomatic, assistance needed 4. = Hospitalized, no oxygen needed 5. = Hospitalized, oxygen by mask or nasal prongs 6. = Hospitalized, oxygen by NIV or high flow 7. = Intubation and mechanical ventilation, pO2/FiO2 ≥150 or SpO2/FiO2 ≥200 8. = Mechanical ventilation, pO2/FiO2 \<150 (SpO2/FiO2 \<200) or vasopressors 9. = Mechanical ventilation, pO2/FiO2 \<150 and vasopressors, dialysis or ECMO 10. = Dead
Time frame: Baseline through Day 7 after completion of therapy
Population: 2 Participants in the Magnesium Citrate arm and 3 participants in the placebo arm were discharged prior to Day 7. No data was collected from them for this outcome measure
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Magnesium Citrate Plus a Probiotic Arm: | COVID Ordinal Outcome Scale | Outcome Score = 3 | 2 Participants |
| Magnesium Citrate Plus a Probiotic Arm: | COVID Ordinal Outcome Scale | Outcome Score = 6 | 2 Participants |
| Magnesium Citrate Plus a Probiotic Arm: | COVID Ordinal Outcome Scale | Outcome Score = 2 | 1 Participants |
| Magnesium Citrate Plus a Probiotic Arm: | COVID Ordinal Outcome Scale | Outcome Score = 7 | 0 Participants |
| Magnesium Citrate Plus a Probiotic Arm: | COVID Ordinal Outcome Scale | Outcome Score = 4 | 0 Participants |
| Magnesium Citrate Plus a Probiotic Arm: | COVID Ordinal Outcome Scale | Outcome Score = 8 | 0 Participants |
| Magnesium Citrate Plus a Probiotic Arm: | COVID Ordinal Outcome Scale | Outcome Score = 1 | 0 Participants |
| Magnesium Citrate Plus a Probiotic Arm: | COVID Ordinal Outcome Scale | Outcome Score = 9 | 0 Participants |
| Magnesium Citrate Plus a Probiotic Arm: | COVID Ordinal Outcome Scale | Outcome Score = 5 | 1 Participants |
| Magnesium Citrate Plus a Probiotic Arm: | COVID Ordinal Outcome Scale | Outcome Score = 10 | 0 Participants |
| Magnesium Citrate Plus a Probiotic Arm: | COVID Ordinal Outcome Scale | Outcome Score = 0 | 0 Participants |
| Placebo | COVID Ordinal Outcome Scale | Outcome Score = 10 | 0 Participants |
| Placebo | COVID Ordinal Outcome Scale | Outcome Score = 0 | 0 Participants |
| Placebo | COVID Ordinal Outcome Scale | Outcome Score = 1 | 0 Participants |
| Placebo | COVID Ordinal Outcome Scale | Outcome Score = 2 | 1 Participants |
| Placebo | COVID Ordinal Outcome Scale | Outcome Score = 3 | 1 Participants |
| Placebo | COVID Ordinal Outcome Scale | Outcome Score = 4 | 0 Participants |
| Placebo | COVID Ordinal Outcome Scale | Outcome Score = 5 | 1 Participants |
| Placebo | COVID Ordinal Outcome Scale | Outcome Score = 6 | 4 Participants |
| Placebo | COVID Ordinal Outcome Scale | Outcome Score = 7 | 0 Participants |
| Placebo | COVID Ordinal Outcome Scale | Outcome Score = 8 | 0 Participants |
| Placebo | COVID Ordinal Outcome Scale | Outcome Score = 9 | 0 Participants |
Secondary
Change in Oxygen Requirements From Baseline to Day 7 by Treatment Group
Measured by liters of oxygen per minute to maintain saturation above 90%
Time frame: baseline and 7 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Magnesium Citrate Plus a Probiotic Arm: | Change in Oxygen Requirements From Baseline to Day 7 by Treatment Group | 2.00 liters per minute |
| Placebo | Change in Oxygen Requirements From Baseline to Day 7 by Treatment Group | 9.00 liters per minute |