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Study of Immunomodulation Using Naltrexone and Ketamine for COVID-19 (SINK COVID-19)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04365985
Recruitment Status : Terminated (Because of the decrease in COVID cases, enrollment is extremely low. Given the current study design, it is not possible to gather data necessary to answer the question about whether study treatment reduces mortality)
First Posted : April 28, 2020
Results First Posted : January 26, 2022
Last Update Posted : January 26, 2022
Sponsor:
Information provided by (Responsible Party):
Matthew Sims, MD, PhD, William Beaumont Hospitals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Factorial Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions COVID-19
Acute Respiratory Distress Syndrome
Severe Acute Respiratory Syndrome (SARS)
Coronavirus Infections
Interventions Drug: Naltrexone
Drug: Ketamine
Other: Placebo
Enrollment 70
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Naltrexone Ketamine
Hide Arm/Group Description

Placebo by mouth 1 time per day for patients with stage I or stage 2A COVID-19

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.

Naltrexone 4.5 mg by mouth 1 time per day for patients with stage I or stage 2A COVID-19.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatient participants with mild/moderate COVID-19 infection stages. Naltrexone will continue for 1 month post hospital discharge. Patients progressing to requirement for advanced oxygenation will be reassess when sedation and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation and can be held when sedation and symptoms of withdrawal is an issue..

Ketamine IV infusion (0.15 mg/kg maximum 20 mg every 6 hours) for patients with stage 2B or 3 COVID-19; may be increased to 0.3 mg/kg to a maximum of 30 mg every 6 hours if needed. Patients entering this arm from the placebo or naltrexone arms remain on those medications as well.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatients with mild/moderate COVID-19. Naltrexone will continue for 1 month post discharge. Patients progressing to requirement for advanced oxygenation will be reassessed and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation .

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.
Period Title: Overall Study
Started 9 9 52
Completed 9 9 52
Not Completed 0 0 0
Arm/Group Title Placebo Naltrexone Ketamine Total
Hide Arm/Group Description

Placebo by mouth 1 time per day for patients with stage I or stage 2A COVID-19

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.

Naltrexone 4.5 mg by mouth 1 time per day for patients with stage I or stage 2A COVID-19.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatient participants with mild/moderate COVID-19 infection stages. Naltrexone will continue for 1 month post hospital discharge. Patients progressing to requirement for advanced oxygenation will be reassess when sedation and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation and can be held when sedation and symptoms of withdrawal is an issue..

Ketamine IV infusion (0.15 mg/kg maximum 20 mg every 6 hours) for patients with stage 2B or 3 COVID-19; may be increased to 0.3 mg/kg to a maximum of 30 mg every 6 hours if needed. Patients entering this arm from the placebo or naltrexone arms remain on those medications as well.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatients with mild/moderate COVID-19. Naltrexone will continue for 1 month post discharge. Patients progressing to requirement for advanced oxygenation will be reassessed and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation .

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.

 Total of all reporting groups
Overall Number of Baseline Participants 9 9 52 70
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 9 participants 9 participants 52 participants 70 participants
65.45  (16.29) 68.52  (10.00) 68.11  (13.20) 67.82  (13.12)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 9 participants 52 participants 70 participants
Female
4
  44.4%
4
  44.4%
18
  34.6%
26
  37.1%
Male
5
  55.6%
5
  55.6%
34
  65.4%
44
  62.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 9 participants 52 participants 70 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
2
   3.8%
2
   2.9%
Not Hispanic or Latino
8
  88.9%
8
  88.9%
44
  84.6%
60
  85.7%
Unknown or Not Reported
1
  11.1%
1
  11.1%
6
  11.5%
8
  11.4%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 9 participants 52 participants 70 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
  33.3%
1
  11.1%
10
  19.2%
14
  20.0%
White
6
  66.7%
7
  77.8%
32
  61.5%
45
  64.3%
More than one race
0
   0.0%
0
   0.0%
8
  15.4%
8
  11.4%
Unknown or Not Reported
0
   0.0%
1
  11.1%
2
   3.8%
3
   4.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 9 participants 9 participants 52 participants 70 participants
9 9 52 70
1.Primary Outcome
Title Progression of Oxygenation Needs
Hide Description Count of participants initially presenting with mild/moderate disease who progress to requiring advanced oxygenation (high flow nasal canula, non-rebreather, continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), or intubation)
Time Frame up to 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Naltrexone Ketamine
Hide Arm/Group Description:

Placebo by mouth 1 time per day for patients with stage I or stage 2A COVID-19

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.

Naltrexone 4.5 mg by mouth 1 time per day for patients with stage I or stage 2A COVID-19.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatient participants with mild/moderate COVID-19 infection stages. Naltrexone will continue for 1 month post hospital discharge. Patients progressing to requirement for advanced oxygenation will be reassess when sedation and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation and can be held when sedation and symptoms of withdrawal is an issue..

Ketamine IV infusion (0.15 mg/kg maximum 20 mg every 6 hours) for patients with stage 2B or 3 COVID-19; may be increased to 0.3 mg/kg to a maximum of 30 mg every 6 hours if needed. Patients entering this arm from the placebo or naltrexone arms remain on those medications as well.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatients with mild/moderate COVID-19. Naltrexone will continue for 1 month post discharge. Patients progressing to requirement for advanced oxygenation will be reassessed and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation .

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.
Overall Number of Participants Analyzed 9 9 52
Measure Type: Count of Participants
Unit of Measure: Participants
1
  11.1%
0
   0.0%
21
  40.4%
2.Secondary Outcome
Title Renal Failure
Hide Description Count of participants who develop or experience worsened renal failure as defined by RIFLE criteria, a 5-point scale where the categories are labeled: Risk-Injury-Failure-Loss-End stage renal disease, with Risk being the least severe and End stage renal disease being the most severe. The criteria for determination of stage are factors of serum creatinine and urine output. Numbers of participants worsening one or more RIFLE stages will be reported.
Time Frame up to 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
Missing data for 4 patients in Ketamine group
Arm/Group Title Placebo Naltrexone Ketamine
Hide Arm/Group Description:

Placebo by mouth 1 time per day for patients with stage I or stage 2A COVID-19

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.

Naltrexone 4.5 mg by mouth 1 time per day for patients with stage I or stage 2A COVID-19.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatient participants with mild/moderate COVID-19 infection stages. Naltrexone will continue for 1 month post hospital discharge. Patients progressing to requirement for advanced oxygenation will be reassess when sedation and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation and can be held when sedation and symptoms of withdrawal is an issue..

Ketamine IV infusion (0.15 mg/kg maximum 20 mg every 6 hours) for patients with stage 2B or 3 COVID-19; may be increased to 0.3 mg/kg to a maximum of 30 mg every 6 hours if needed. Patients entering this arm from the placebo or naltrexone arms remain on those medications as well.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatients with mild/moderate COVID-19. Naltrexone will continue for 1 month post discharge. Patients progressing to requirement for advanced oxygenation will be reassessed and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation .

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.
Overall Number of Participants Analyzed 9 9 48
Measure Type: Count of Participants
Unit of Measure: Participants
1
  11.1%
0
   0.0%
12
  25.0%
3.Secondary Outcome
Title Liver Failure
Hide Description Count of participants who develop or experience worsened liver failure as defined by serum transaminases five times normal limits
Time Frame up to 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
Missing data for 4 patients in Ketamine group
Arm/Group Title Placebo Naltrexone Ketamine
Hide Arm/Group Description:

Placebo by mouth 1 time per day for patients with stage I or stage 2A COVID-19

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.

Naltrexone 4.5 mg by mouth 1 time per day for patients with stage I or stage 2A COVID-19.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatient participants with mild/moderate COVID-19 infection stages. Naltrexone will continue for 1 month post hospital discharge. Patients progressing to requirement for advanced oxygenation will be reassess when sedation and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation and can be held when sedation and symptoms of withdrawal is an issue..

Ketamine IV infusion (0.15 mg/kg maximum 20 mg every 6 hours) for patients with stage 2B or 3 COVID-19; may be increased to 0.3 mg/kg to a maximum of 30 mg every 6 hours if needed. Patients entering this arm from the placebo or naltrexone arms remain on those medications as well.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatients with mild/moderate COVID-19. Naltrexone will continue for 1 month post discharge. Patients progressing to requirement for advanced oxygenation will be reassessed and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation .

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.
Overall Number of Participants Analyzed 9 9 48
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
4
   8.3%
4.Secondary Outcome
Title Cytokine Storm
Hide Description Count of participants who develop cytokine storm as measured by elevated markers of inflammation (elevated D-dimer, hypofibrinogenemia, hyperferritinemia), evidence of acute respiratory distress syndrome (ARDS) measured by imaging findings and mechanical ventilator requirements, and/or continuous fever (≥ 38.1 ° Celsius unremitting)
Time Frame up to 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
Missing data for 4 patients in Ketamine group
Arm/Group Title Placebo Naltrexone Ketamine
Hide Arm/Group Description:

Placebo by mouth 1 time per day for patients with stage I or stage 2A COVID-19

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.

Naltrexone 4.5 mg by mouth 1 time per day for patients with stage I or stage 2A COVID-19.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatient participants with mild/moderate COVID-19 infection stages. Naltrexone will continue for 1 month post hospital discharge. Patients progressing to requirement for advanced oxygenation will be reassess when sedation and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation and can be held when sedation and symptoms of withdrawal is an issue..

Ketamine IV infusion (0.15 mg/kg maximum 20 mg every 6 hours) for patients with stage 2B or 3 COVID-19; may be increased to 0.3 mg/kg to a maximum of 30 mg every 6 hours if needed. Patients entering this arm from the placebo or naltrexone arms remain on those medications as well.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatients with mild/moderate COVID-19. Naltrexone will continue for 1 month post discharge. Patients progressing to requirement for advanced oxygenation will be reassessed and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation .

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.
Overall Number of Participants Analyzed 9 9 48
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
5.Secondary Outcome
Title COVID Mortality
Hide Description Count of participants who die from COVID-19
Time Frame up to 1 month post hospital discharge
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Naltrexone Ketamine
Hide Arm/Group Description:

Placebo by mouth 1 time per day for patients with stage I or stage 2A COVID-19

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.

Naltrexone 4.5 mg by mouth 1 time per day for patients with stage I or stage 2A COVID-19.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatient participants with mild/moderate COVID-19 infection stages. Naltrexone will continue for 1 month post hospital discharge. Patients progressing to requirement for advanced oxygenation will be reassess when sedation and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation and can be held when sedation and symptoms of withdrawal is an issue..

Ketamine IV infusion (0.15 mg/kg maximum 20 mg every 6 hours) for patients with stage 2B or 3 COVID-19; may be increased to 0.3 mg/kg to a maximum of 30 mg every 6 hours if needed. Patients entering this arm from the placebo or naltrexone arms remain on those medications as well.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatients with mild/moderate COVID-19. Naltrexone will continue for 1 month post discharge. Patients progressing to requirement for advanced oxygenation will be reassessed and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation .

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.
Overall Number of Participants Analyzed 9 9 52
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
16
  30.8%
6.Secondary Outcome
Title Length of Hospital Stay
Hide Description Length of hospital stay in days
Time Frame up to 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
Admission data not collected for Placebo and Naltrexone patients. Missing discharge data for 5 patients in ketamine group.
Arm/Group Title Placebo Naltrexone Ketamine
Hide Arm/Group Description:

Placebo by mouth 1 time per day for patients with stage I or stage 2A COVID-19

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.

Naltrexone 4.5 mg by mouth 1 time per day for patients with stage I or stage 2A COVID-19.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatient participants with mild/moderate COVID-19 infection stages. Naltrexone will continue for 1 month post hospital discharge. Patients progressing to requirement for advanced oxygenation will be reassess when sedation and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation and can be held when sedation and symptoms of withdrawal is an issue..

Ketamine IV infusion (0.15 mg/kg maximum 20 mg every 6 hours) for patients with stage 2B or 3 COVID-19; may be increased to 0.3 mg/kg to a maximum of 30 mg every 6 hours if needed. Patients entering this arm from the placebo or naltrexone arms remain on those medications as well.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatients with mild/moderate COVID-19. Naltrexone will continue for 1 month post discharge. Patients progressing to requirement for advanced oxygenation will be reassessed and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation .

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.
Overall Number of Participants Analyzed 0 0 47
Mean (Standard Deviation)
Unit of Measure: days
21.37  (15.89)
7.Secondary Outcome
Title Intensive Care Unit (ICU) Admission
Hide Description Count of patients admitted to the ICU at any time during index hospitalization
Time Frame up to 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
Data not available for 1 patient in Naltrexone group and 5 patients in Ketamine group
Arm/Group Title Placebo Naltrexone Ketamine
Hide Arm/Group Description:

Placebo by mouth 1 time per day for patients with stage I or stage 2A COVID-19

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.

Naltrexone 4.5 mg by mouth 1 time per day for patients with stage I or stage 2A COVID-19.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatient participants with mild/moderate COVID-19 infection stages. Naltrexone will continue for 1 month post hospital discharge. Patients progressing to requirement for advanced oxygenation will be reassess when sedation and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation and can be held when sedation and symptoms of withdrawal is an issue..

Ketamine IV infusion (0.15 mg/kg maximum 20 mg every 6 hours) for patients with stage 2B or 3 COVID-19; may be increased to 0.3 mg/kg to a maximum of 30 mg every 6 hours if needed. Patients entering this arm from the placebo or naltrexone arms remain on those medications as well.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatients with mild/moderate COVID-19. Naltrexone will continue for 1 month post discharge. Patients progressing to requirement for advanced oxygenation will be reassessed and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation .

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.
Overall Number of Participants Analyzed 9 8 47
Measure Type: Count of Participants
Unit of Measure: Participants
2
  22.2%
1
  12.5%
28
  59.6%
8.Secondary Outcome
Title Intensive Care Unit (ICU) Duration
Hide Description Length of ICU stay in days
Time Frame up to 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
Patient in naltrexone group admitted to ICU had length of stay=0
Arm/Group Title Placebo Naltrexone Ketamine
Hide Arm/Group Description:

Placebo by mouth 1 time per day for patients with stage I or stage 2A COVID-19

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.

Naltrexone 4.5 mg by mouth 1 time per day for patients with stage I or stage 2A COVID-19.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatient participants with mild/moderate COVID-19 infection stages. Naltrexone will continue for 1 month post hospital discharge. Patients progressing to requirement for advanced oxygenation will be reassess when sedation and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation and can be held when sedation and symptoms of withdrawal is an issue..

Ketamine IV infusion (0.15 mg/kg maximum 20 mg every 6 hours) for patients with stage 2B or 3 COVID-19; may be increased to 0.3 mg/kg to a maximum of 30 mg every 6 hours if needed. Patients entering this arm from the placebo or naltrexone arms remain on those medications as well.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatients with mild/moderate COVID-19. Naltrexone will continue for 1 month post discharge. Patients progressing to requirement for advanced oxygenation will be reassessed and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation .

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.
Overall Number of Participants Analyzed 2 1 28
Mean (Standard Deviation)
Unit of Measure: days
2.56  (0.71) 0  (0) 16.68  (11.25)
9.Secondary Outcome
Title Intubation
Hide Description Count of participants requiring intubation
Time Frame up to 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Naltrexone Ketamine
Hide Arm/Group Description:

Placebo by mouth 1 time per day for patients with stage I or stage 2A COVID-19

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.

Naltrexone 4.5 mg by mouth 1 time per day for patients with stage I or stage 2A COVID-19.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatient participants with mild/moderate COVID-19 infection stages. Naltrexone will continue for 1 month post hospital discharge. Patients progressing to requirement for advanced oxygenation will be reassess when sedation and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation and can be held when sedation and symptoms of withdrawal is an issue..

Ketamine IV infusion (0.15 mg/kg maximum 20 mg every 6 hours) for patients with stage 2B or 3 COVID-19; may be increased to 0.3 mg/kg to a maximum of 30 mg every 6 hours if needed. Patients entering this arm from the placebo or naltrexone arms remain on those medications as well.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatients with mild/moderate COVID-19. Naltrexone will continue for 1 month post discharge. Patients progressing to requirement for advanced oxygenation will be reassessed and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation .

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.
Overall Number of Participants Analyzed 9 9 52
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
1
  11.1%
29
  55.8%
10.Secondary Outcome
Title Intubation Duration
Hide Description Length of intubation, measured in days
Time Frame up to 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
No patients in Placebo group were intubated. For those intubated, data not available for 4 patients of 29 intubated in the Ketamine group
Arm/Group Title Placebo Naltrexone Ketamine
Hide Arm/Group Description:

Placebo by mouth 1 time per day for patients with stage I or stage 2A COVID-19

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.

Naltrexone 4.5 mg by mouth 1 time per day for patients with stage I or stage 2A COVID-19.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatient participants with mild/moderate COVID-19 infection stages. Naltrexone will continue for 1 month post hospital discharge. Patients progressing to requirement for advanced oxygenation will be reassess when sedation and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation and can be held when sedation and symptoms of withdrawal is an issue..

Ketamine IV infusion (0.15 mg/kg maximum 20 mg every 6 hours) for patients with stage 2B or 3 COVID-19; may be increased to 0.3 mg/kg to a maximum of 30 mg every 6 hours if needed. Patients entering this arm from the placebo or naltrexone arms remain on those medications as well.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatients with mild/moderate COVID-19. Naltrexone will continue for 1 month post discharge. Patients progressing to requirement for advanced oxygenation will be reassessed and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation .

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.
Overall Number of Participants Analyzed 0 1 25
Mean (Standard Deviation)
Unit of Measure: days
3.32  (0) 15.53  (14.12)
11.Secondary Outcome
Title Time Until Recovery
Hide Description Time measured in days from hospital admission to determination patient is stable for discharge
Time Frame up to 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
Patients not included who died during admission. Of 28 patients in ketamine group surviving to discharge, data missing for 5 patients. Of 8 patients in naltrexone group surviving to discharge, data missing for 1 patient.
Arm/Group Title Placebo Naltrexone Ketamine
Hide Arm/Group Description:

Placebo by mouth 1 time per day for patients with stage I or stage 2A COVID-19

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.

Naltrexone 4.5 mg by mouth 1 time per day for patients with stage I or stage 2A COVID-19.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatient participants with mild/moderate COVID-19 infection stages. Naltrexone will continue for 1 month post hospital discharge. Patients progressing to requirement for advanced oxygenation will be reassess when sedation and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation and can be held when sedation and symptoms of withdrawal is an issue..

Ketamine IV infusion (0.15 mg/kg maximum 20 mg every 6 hours) for patients with stage 2B or 3 COVID-19; may be increased to 0.3 mg/kg to a maximum of 30 mg every 6 hours if needed. Patients entering this arm from the placebo or naltrexone arms remain on those medications as well.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatients with mild/moderate COVID-19. Naltrexone will continue for 1 month post discharge. Patients progressing to requirement for advanced oxygenation will be reassessed and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation .

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.
Overall Number of Participants Analyzed 9 7 23
Mean (Standard Deviation)
Unit of Measure: days
8.67  (5.79) 8.71  (7.91) 17.57  (22.14)
Time Frame 1 month
Adverse Event Reporting Description Systematic assessment of adverse events by review of medical records
 
Arm/Group Title Placebo Naltrexone Ketamine
Hide Arm/Group Description

Placebo by mouth 1 time per day for patients with stage I or stage 2A COVID-19

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.

Naltrexone 4.5 mg by mouth 1 time per day for patients with stage I or stage 2A COVID-19.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatient participants with mild/moderate COVID-19 infection stages. Naltrexone will continue for 1 month post hospital discharge. Patients progressing to requirement for advanced oxygenation will be reassess when sedation and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation and can be held when sedation and symptoms of withdrawal is an issue..

Ketamine IV infusion (0.15 mg/kg maximum 20 mg every 6 hours) for patients with stage 2B or 3 COVID-19; may be increased to 0.3 mg/kg to a maximum of 30 mg every 6 hours if needed. Patients entering this arm from the placebo or naltrexone arms remain on those medications as well.

Naltrexone: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatients with mild/moderate COVID-19. Naltrexone will continue for 1 month post discharge. Patients progressing to requirement for advanced oxygenation will be reassessed and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation .

Placebo: Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.
All-Cause Mortality
Placebo Naltrexone Ketamine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/9 (0.00%)      1/9 (11.11%)      24/52 (46.15%)    
Hide Serious Adverse Events
Placebo Naltrexone Ketamine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/9 (44.44%)      9/9 (100.00%)      52/52 (100.00%)    
Blood and lymphatic system disorders       
ACUTE ANEMIA †  0/9 (0.00%)  0 0/9 (0.00%)  0 1/52 (1.92%)  1
ANEMIA †  0/9 (0.00%)  0 0/9 (0.00%)  0 1/52 (1.92%)  1
ANEMIA REQUIRING TRANSFUSION †  0/9 (0.00%)  0 0/9 (0.00%)  0 2/52 (3.85%)  2
HEMORRHAGE †  0/9 (0.00%)  0 0/9 (0.00%)  0 1/52 (1.92%)  1
HEMORRHAGIC SHOCK †  0/9 (0.00%)  0 0/9 (0.00%)  0 3/52 (5.77%)  3
HYPERKALEMIA †  0/9 (0.00%)  0 0/9 (0.00%)  0 2/52 (3.85%)  2
HYPOTENSION †  0/9 (0.00%)  0 0/9 (0.00%)  0 5/52 (9.62%)  5
LABILE HYPOTENSION †  0/9 (0.00%)  0 0/9 (0.00%)  0 1/52 (1.92%)  1
SHOCK †  0/9 (0.00%)  0 0/9 (0.00%)  0 5/52 (9.62%)  5
BACTEREMIA, STAPHLOCOCCUS EPIDERMIS †  0/9 (0.00%)  0 0/9 (0.00%)  0 1/52 (1.92%)  1
Cardiac disorders       
ACUTE CARDIAC ARREST DUE TO ARRYTHMIA †  0/9 (0.00%)  0 0/9 (0.00%)  0 1/52 (1.92%)  1
ACUTE CARDIOPULMONARY ARREST †  0/9 (0.00%)  0 0/9 (0.00%)  0 1/52 (1.92%)  1
ASYSTOLE †  0/9 (0.00%)  0 0/9 (0.00%)  0 1/52 (1.92%)  1
ATRIAL FIBRILLATION †  0/9 (0.00%)  0 1/9 (11.11%)  1 1/52 (1.92%)  1
CARDIAC ARREST †  0/9 (0.00%)  0 1/9 (11.11%)  1 2/52 (3.85%)  2
CARDIOGENIC SHOCK SECONDARY TO ATRIAL FIBRILLATION WITH RAPID VENTRICULAR RESPONSE †  0/9 (0.00%)  0 1/9 (11.11%)  1 1/52 (1.92%)  1
CARDIOPULMONARY ARREST †  0/9 (0.00%)  0 0/9 (0.00%)  0 2/52 (3.85%)  2
CARDIOPULMONARY FAILURE †  0/9 (0.00%)  0 0/9 (0.00%)  0 2/52 (3.85%)  2
TACHYCARDIS †  0/9 (0.00%)  0 0/9 (0.00%)  0 1/52 (1.92%)  1
UNSTABLE ARRYTHMIA †  0/9 (0.00%)  0 0/9 (0.00%)  0 1/52 (1.92%)  1
Gastrointestinal disorders       
GASTROINTESTINAL BLEED †  0/9 (0.00%)  0 0/9 (0.00%)  0 2/52 (3.85%)  2
Infections and infestations       
METHYCILLIN-RESISTANT STAPHLOCOCCUS AUREUS BACTEREMIA †  0/9 (0.00%)  0 0/9 (0.00%)  0 1/52 (1.92%)  1
PROGRESSION OF COVID-19 †  0/9 (0.00%)  0 0/9 (0.00%)  0 1/52 (1.92%)  1
SEPSIS †  0/9 (0.00%)  0 0/9 (0.00%)  0 1/52 (1.92%)  1
SEPTIC SHOCK †  0/9 (0.00%)  0 0/9 (0.00%)  0 2/52 (3.85%)  2
SEPTIC SHOCK SECONDARY TO METHICILLIN-SUSCEPTIBLE STAPHYLOCOCCUS AUREUS †  0/9 (0.00%)  0 0/9 (0.00%)  0 1/52 (1.92%)  1
SEVERE SEPSIS †  0/9 (0.00%)  0 0/9 (0.00%)  0 1/52 (1.92%)  1
Injury, poisoning and procedural complications       
FALL †  0/9 (0.00%)  0 1/9 (11.11%)  1 0/52 (0.00%)  0
Musculoskeletal and connective tissue disorders       
CRITICAL ILLNESS MYOPATHY †  1/9 (11.11%)  1 3/9 (33.33%)  3 6/52 (11.54%)  6
Nervous system disorders       
ACUTE CEREBRAL EDEMA AND ACUTE ENCEPHALOPATHY RELATED TO SUBACUTE INFARCT †  0/9 (0.00%)  0 0/9 (0.00%)  0 1/52 (1.92%)  1
SEIZURE †  0/9 (0.00%)  0 0/9 (0.00%)  0 1/52 (1.92%)  1
SEVERE METABOLIC ENCEPHALOPATHY †  1/9 (11.11%)  1 0/9 (0.00%)  0 0/52 (0.00%)  0
TOXIC METABOLIC ENCEPHALOPATHY †  0/9 (0.00%)  0 0/9 (0.00%)  0 1/52 (1.92%)  1
TREMOR †  1/9 (11.11%)  1 0/9 (0.00%)  0 0/52 (0.00%)  0
Renal and urinary disorders       
ACUTE RENAL FAILURE †  0/9 (0.00%)  0 0/9 (0.00%)  0 2/52 (3.85%)  2
OLIGOURIA †  0/9 (0.00%)  0 0/9 (0.00%)  0 1/52 (1.92%)  1
RENAL FAILURE †  0/9 (0.00%)  0 0/9 (0.00%)  0 2/52 (3.85%)  2
Respiratory, thoracic and mediastinal disorders       
ACUTE RESPIRATORY FAILURE †  0/9 (0.00%)  0 1/9 (11.11%)  1 3/52 (5.77%)  3
ASPIRATION PNEUMONITIS †  0/9 (0.00%)  0 1/9 (11.11%)  1 0/52 (0.00%)  0
PNEUMONIA, EXTENDED-SPECTRUM BETA-LACTAMASE (ESBL) E COLI †  0/9 (0.00%)  0 0/9 (0.00%)  0 1/52 (1.92%)  1
PNEUMONIA †  0/9 (0.00%)  0 0/9 (0.00%)  0 2/52 (3.85%)  2
PULMONARY EMBOLISM †  0/9 (0.00%)  0 0/9 (0.00%)  0 2/52 (3.85%)  2
PULMONARY EDEMA †  1/9 (11.11%)  1 0/9 (0.00%)  0 0/52 (0.00%)  0
RESPIRATORY FAILURE †  0/9 (0.00%)  0 0/9 (0.00%)  0 10/52 (19.23%)  10
SHORTNESS OF BREATH †  0/9 (0.00%)  0 1/9 (11.11%)  1 0/52 (0.00%)  0
TRACHEAL EDEMA †  0/9 (0.00%)  0 0/9 (0.00%)  0 1/52 (1.92%)  1
Vascular disorders       
DEEP VEIN THROMBOSIS †  0/9 (0.00%)  0 1/9 (11.11%)  1 0/52 (0.00%)  0
HEMATOMA †  0/9 (0.00%)  0 0/9 (0.00%)  0 1/52 (1.92%)  1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Naltrexone Ketamine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/9 (100.00%)      7/9 (77.78%)      52/52 (100.00%)    
Blood and lymphatic system disorders       
BLEEDING †  0/9 (0.00%)  0 0/9 (0.00%)  0 10/52 (19.23%)  10
EPITAXIS †  1/9 (11.11%)  1 0/9 (0.00%)  0 3/52 (5.77%)  3
THROMBOCYTOPENIA †  1/9 (11.11%)  1 0/9 (0.00%)  0 3/52 (5.77%)  3
Cardiac disorders       
ATRIAL FIBRILLATION WITH RAPID VENTRICULAR RATE †  1/9 (11.11%)  1 0/9 (0.00%)  0 5/52 (9.62%)  5
CHEST PAIN †  2/9 (22.22%)  2 0/9 (0.00%)  0 1/52 (1.92%)  1
ELEVATED HEART RATE/BLOOD PRESSURE †  1/9 (11.11%)  1 0/9 (0.00%)  0 0/52 (0.00%)  0
HYPOTENSION †  1/9 (11.11%)  1 0/9 (0.00%)  0 3/52 (5.77%)  3
VENTRICULAR TACHYCARDIA †  0/9 (0.00%)  0 0/9 (0.00%)  0 4/52 (7.69%)  4
Gastrointestinal disorders       
EMESIS, ONE EPISODE †  1/9 (11.11%)  1 0/9 (0.00%)  0 1/52 (1.92%)  1
EMESIS, FIVE EPISODES †  1/9 (11.11%)  1 0/9 (0.00%)  0 0/52 (0.00%)  0
MELENA †  1/9 (11.11%)  1 1/9 (11.11%)  1 1/52 (1.92%)  1
General disorders       
FEVER †  1/9 (11.11%)  1 0/9 (0.00%)  0 3/52 (5.77%)  3
LETHARGY, INCREASED †  1/9 (11.11%)  1 0/9 (0.00%)  0 0/52 (0.00%)  0
XEROSTOMIA †  0/9 (0.00%)  0 1/9 (11.11%)  1 0/52 (0.00%)  0
Injury, poisoning and procedural complications       
FALL †  2/9 (22.22%)  2 1/9 (11.11%)  1 0/52 (0.00%)  0
PAIN, WRIST †  1/9 (11.11%)  1 0/9 (0.00%)  0 0/52 (0.00%)  0
Musculoskeletal and connective tissue disorders       
CRITICAL ILLNESS MYOPATHY †  1/9 (11.11%)  1 0/9 (0.00%)  0 4/52 (7.69%)  4
Nervous system disorders       
DIZZINESS †  0/9 (0.00%)  0 1/9 (11.11%)  1 0/52 (0.00%)  0
HEADACHE †  1/9 (11.11%)  1 0/9 (0.00%)  0 1/52 (1.92%)  1
TREMOR †  0/9 (0.00%)  0 1/9 (11.11%)  1 1/52 (1.92%)  1
Psychiatric disorders       
AGITATION †  0/9 (0.00%)  0 0/9 (0.00%)  0 3/52 (5.77%)  3
ALTERED MENTAL STATUS †  1/9 (11.11%)  1 0/9 (0.00%)  0 1/52 (1.92%)  1
Renal and urinary disorders       
HEMATURIA †  1/9 (11.11%)  1 0/9 (0.00%)  0 2/52 (3.85%)  2
URINARY RETENTION †  1/9 (11.11%)  1 0/9 (0.00%)  0 0/52 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
HEMOPTYSIS †  1/9 (11.11%)  1 0/9 (0.00%)  0 0/52 (0.00%)  0
PULMONARY EMBOLISM †  1/9 (11.11%)  1 0/9 (0.00%)  0 0/52 (0.00%)  0
SHORTNESS OF BREATH †  1/9 (11.11%)  1 0/9 (0.00%)  0 0/52 (0.00%)  0
Skin and subcutaneous tissue disorders       
CYST, LOWER EXTREMITY †  0/9 (0.00%)  0 1/9 (11.11%)  1 0/52 (0.00%)  0
DECUBITUS ULCER †  0/9 (0.00%)  0 0/9 (0.00%)  0 3/52 (5.77%)  3
RASH †  1/9 (11.11%)  1 0/9 (0.00%)  0 5/52 (9.62%)  5
Vascular disorders       
DEEP VEIN THROMBOSIS †  0/9 (0.00%)  0 1/9 (11.11%)  1 0/52 (0.00%)  0
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Matthew Sims, MD
Organization: William Beaumont Hospitals
Phone: 248 551-0027
EMail: matthew.sims@beaumont.org
Layout table for additonal information
Responsible Party: Matthew Sims, MD, PhD, William Beaumont Hospitals
ClinicalTrials.gov Identifier: NCT04365985    
Other Study ID Numbers: 2020-097
First Submitted: April 26, 2020
First Posted: April 28, 2020
Results First Submitted: January 12, 2022
Results First Posted: January 26, 2022
Last Update Posted: January 26, 2022