Trial Outcomes & Findings for Impact of Colchicine and Low-dose Naltrexone on COVID-19 (NCT NCT04756128)

Results Overview

Disease recovery from moderate COVID-19 was defined as achieving a clinical scale score of 1 (indicating the patient no longer required hospital-level care for COVID-19. Attainment of a score of 1 by study day 5 was chosen based on initial experience treating COVID-19 within this specific health system-patients with similar disease severity were typically hospitalized for 6-7 days, and time from admission to enrollment in preceding COVID-19 studies was generally 1-2 days.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

142 participants

Primary outcome timeframe

Assessed from time of hospitalization until (1) 5 days after enrollment, while still hospitalized (or until discharge, which may be less than 5 days)

Results posted on

2023-07-25

Participant Flow

Participant milestones

Participant milestones
Measure	Colchicine-Only Arm Patients randomized to a colchicine-containing treatment arm will receive colchicine 0.6 mg twice daily for up to 28 days. Patients experiencing gastrointestinal side effects (nausea, vomiting, and diarrhea) on twice daily dosing may have the dose decreased to 0.6 mg daily. Dosing will continue twice daily unless there is a change that requires a dose adjustment or an exclusion criterion is met. Dosing deviations above the study protocol will be allowed if medically necessary for the treatment of an additional indication (e.g. colchicine for viral pericarditis). Patients in this arm will also receive the investigating institution's current standard of care (described in detail in the "standard of care" arm) for patients with COVID-19. Colchicine 0.6 mg: Colchicine is an oral anti-inflammatory agent that is relatively inexpensive, readily available, and has been used for generations. Approved for treatment and prophylaxis of gout flares and Mediterranean fever, it is also used in a variety of other inflammatory conditions (e.g. pericarditis and diffuse vascular inflammation such as Behcet syndrome). Colchicine binds to tubulin causing depolymerization, which interferes with neutrophil chemotaxis, adhesion, and mobilization to sites of inflammation, and contributes to reduction in superoxide production; through interference of the NLRP3 inflammasome protein complex, colchicine inhibits IL-1b, IL-6, and IL-18 production.	Colchicine and Naltrexone ("Combined") Arm Patients randomized to a colchicine-containing treatment arm (including the "combined arm") will receive colchicine 0.6 mg twice daily for up to 28 days. Patients in the "combined" arm will also receive naltrexone. Patients randomized to an LDN-containing treatment arm (including the "combined arm") will receive naltrexone 4.5 mg once daily. Patients in this arm will also receive the investigating institution's current standard of care (described in detail in the "standard of care" arm) for patients with COVID-19. Colchicine 0.6 mg: Colchicine is an oral anti-inflammatory agent that is relatively inexpensive, readily available, and has been used for generations. Approved for treatment and prophylaxis of gout flares and Mediterranean fever, it is also used in a variety of other inflammatory conditions (e.g. pericarditis and diffuse vascular inflammation such as Behcet syndrome). Colchicine binds to tubulin causing depolymerization, which interferes with neutrophil chemotaxis, adhesion, and mobilization to sites of inflammation, and contributes to reduction in superoxide production; through interference of the NLRP3 inflammasome protein complex, colchicine inhibits IL-1b, IL-6, and IL-18 production. Naltrexone: Most well known as an opioid antagonist, or a treatment for alcohol dependence, naltrexone also possesses immunomodulatory effects. Seen exclusively at low doses, this attribute is being employed in the pain community as a novel anti-inflammatory agent.	Naltrexone-Only Arm Patients randomized to an LDN-containing treatment arm (including the "combined arm") will receive naltrexone 4.5 mg once daily. The first dose can be given at any time during the day of enrollment/randomization, and will be timed at 08:00 daily thereafter (with AM colchicine dose, if in combined colchicine/LDN arm) for up to 28 days (unless new contraindication or exclusion criteria met). Patients in this arm will also receive the investigating institution's current standard of care (described in detail in the "standard of care" arm) for patients with COVID-19. Naltrexone: Most well known as an opioid antagonist, or a treatment for alcohol dependence, naltrexone also possesses immunomodulatory effects. Seen exclusively at low doses, this attribute is being employed in the pain community as a novel anti-inflammatory agent that has been shown to reduce symptom severity in fibromyalgia, Crohn's disease, multiple sclerosis, and complex regional pain syndrome. For this study, patients enrolled in a naltrexone-containing arm will take their daily dose of the medication (4.5mg) by oral suspension.	Standard of Care Arm Patients in this arm will receive the investigating institution's current standard of care for patients with COVID-19. For example, all patients requiring supplemental oxygen (assuming no contraindications) would be candidates for both remdesivir 200 mg x 1 IV dose followed the next day by 100 mg q24h IV x up to 4 doses, as well as dexamethasone 6 mg q24h x 10 up to 10 doses.
Overall Study STARTED	35	35	36	36
Overall Study COMPLETED	34	33	35	35
Overall Study NOT COMPLETED	1	2	1	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Impact of Colchicine and Low-dose Naltrexone on COVID-19

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Colchicine-Only Arm n=34 Participants Patients randomized to a colchicine-containing treatment arm will receive colchicine 0.6 mg twice daily for up to 28 days. Patients experiencing gastrointestinal side effects (nausea, vomiting, and diarrhea) on twice daily dosing may have the dose decreased to 0.6 mg daily. Dosing will continue twice daily unless there is a change that requires a dose adjustment or an exclusion criterion is met. Dosing deviations above the study protocol will be allowed if medically necessary for the treatment of an additional indication (e.g. colchicine for viral pericarditis). Patients in this arm will also receive the investigating institution's current standard of care (described in detail in the "standard of care" arm) for patients with COVID-19. Colchicine 0.6 mg: Colchicine is an oral anti-inflammatory agent that is relatively inexpensive, readily available, and has been used for generations. Approved for treatment and prophylaxis of gout flares and Mediterranean fever, it is also used in a variety of other inflammatory conditions (e.g. pericarditis and diffuse vascular inflammation such as Behcet syndrome). Colchicine binds to tubulin causing depolymerization, which interferes with neutrophil chemotaxis, adhesion, and mobilization to sites of inflammation, and contributes to reduction in superoxide production; through interference of the NLRP3 inflammasome protein complex, colchicine inhibits IL-1b, IL-6, and IL-18 production.	Colchicine and Naltrexone ("Combined") Arm n=33 Participants Patients randomized to a colchicine-containing treatment arm (including the "combined arm") will receive colchicine 0.6 mg twice daily for up to 28 days. Patients in the "combined" arm will also receive naltrexone. Patients randomized to an LDN-containing treatment arm (including the "combined arm") will receive naltrexone 4.5 mg once daily. Patients in this arm will also receive the investigating institution's current standard of care (described in detail in the "standard of care" arm) for patients with COVID-19. Colchicine 0.6 mg: Colchicine is an oral anti-inflammatory agent that is relatively inexpensive, readily available, and has been used for generations. Approved for treatment and prophylaxis of gout flares and Mediterranean fever, it is also used in a variety of other inflammatory conditions (e.g. pericarditis and diffuse vascular inflammation such as Behcet syndrome). Colchicine binds to tubulin causing depolymerization, which interferes with neutrophil chemotaxis, adhesion, and mobilization to sites of inflammation, and contributes to reduction in superoxide production; through interference of the NLRP3 inflammasome protein complex, colchicine inhibits IL-1b, IL-6, and IL-18 production. Naltrexone: Most well known as an opioid antagonist, or a treatment for alcohol dependence, naltrexone also possesses immunomodulatory effects. Seen exclusively at low doses, this attribute is being employed in the pain community as a novel anti-inflammatory agent.	Naltrexone-Only Arm n=35 Participants Patients randomized to an LDN-containing treatment arm (including the "combined arm") will receive naltrexone 4.5 mg once daily. The first dose can be given at any time during the day of enrollment/randomization, and will be timed at 08:00 daily thereafter (with AM colchicine dose, if in combined colchicine/LDN arm) for up to 28 days (unless new contraindication or exclusion criteria met). Patients in this arm will also receive the investigating institution's current standard of care (described in detail in the "standard of care" arm) for patients with COVID-19. Naltrexone: Most well known as an opioid antagonist, or a treatment for alcohol dependence, naltrexone also possesses immunomodulatory effects. Seen exclusively at low doses, this attribute is being employed in the pain community as a novel anti-inflammatory agent that has been shown to reduce symptom severity in fibromyalgia, Crohn's disease, multiple sclerosis, and complex regional pain syndrome. For this study, patients enrolled in a naltrexone-containing arm will take their daily dose of the medication (4.5mg) by oral suspension.	Standard of Care Arm n=35 Participants Patients in this arm will receive the investigating institution's current standard of care for patients with COVID-19. For example, all patients requiring supplemental oxygen (assuming no contraindications) would be candidates for both remdesivir 200 mg x 1 IV dose followed the next day by 100 mg q24h IV x up to 4 doses, as well as dexamethasone 6 mg q24h x 10 up to 10 doses.	Total n=137 Participants Total of all reporting groups
Age, Continuous	57 years STANDARD_DEVIATION 11 • n=5 Participants	55 years STANDARD_DEVIATION 15 • n=7 Participants	59 years STANDARD_DEVIATION 16 • n=5 Participants	59 years STANDARD_DEVIATION 16 • n=4 Participants	58 years STANDARD_DEVIATION 15 • n=21 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants	16 Participants n=4 Participants	58 Participants n=21 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	24 Participants n=7 Participants	16 Participants n=5 Participants	19 Participants n=4 Participants	79 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	0 Participants n=4 Participants	10 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=5 Participants	30 Participants n=7 Participants	32 Participants n=5 Participants	35 Participants n=4 Participants	126 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized White	24 Participants n=5 Participants	24 Participants n=7 Participants	24 Participants n=5 Participants	25 Participants n=4 Participants	97 Participants n=21 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	7 Participants n=4 Participants	19 Participants n=21 Participants
Race/Ethnicity, Customized Hispanic	3 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	0 Participants n=4 Participants	8 Participants n=21 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	7 Participants n=21 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Unknown	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Region of Enrollment United States	34 participants n=5 Participants	33 participants n=7 Participants	35 participants n=5 Participants	35 participants n=4 Participants	137 participants n=21 Participants

PRIMARY outcome

Timeframe: Assessed from time of hospitalization until (1) 5 days after enrollment, while still hospitalized (or until discharge, which may be less than 5 days)

Disease recovery from moderate COVID-19 was defined as achieving a clinical scale score of 1 (indicating the patient no longer required hospital-level care for COVID-19. Attainment of a score of 1 by study day 5 was chosen based on initial experience treating COVID-19 within this specific health system-patients with similar disease severity were typically hospitalized for 6-7 days, and time from admission to enrollment in preceding COVID-19 studies was generally 1-2 days.

Outcome measures

Outcome measures
Measure	Colchicine-Only Arm n=34 Participants Patients randomized to a colchicine-containing treatment arm will receive colchicine 0.6 mg twice daily for up to 28 days. Patients experiencing gastrointestinal side effects (nausea, vomiting, and diarrhea) on twice daily dosing may have the dose decreased to 0.6 mg daily. Dosing will continue twice daily unless there is a change that requires a dose adjustment or an exclusion criterion is met. Dosing deviations above the study protocol will be allowed if medically necessary for the treatment of an additional indication (e.g. colchicine for viral pericarditis). Patients in this arm will also receive the investigating institution's current standard of care (described in detail in the "standard of care" arm) for patients with COVID-19. Colchicine 0.6 mg: Colchicine is an oral anti-inflammatory agent that is relatively inexpensive, readily available, and has been used for generations. Approved for treatment and prophylaxis of gout flares and Mediterranean fever, it is also used in a variety of other inflammatory conditions (e.g. pericarditis and diffuse vascular inflammation such as Behcet syndrome). Colchicine binds to tubulin causing depolymerization, which interferes with neutrophil chemotaxis, adhesion, and mobilization to sites of inflammation, and contributes to reduction in superoxide production; through interference of the NLRP3 inflammasome protein complex, colchicine inhibits IL-1b, IL-6, and IL-18 production.	Colchicine and Naltrexone ("Combined") Arm n=33 Participants Patients randomized to a colchicine-containing treatment arm (including the "combined arm") will receive colchicine 0.6 mg twice daily for up to 28 days. Patients in the "combined" arm will also receive naltrexone. Patients randomized to an LDN-containing treatment arm (including the "combined arm") will receive naltrexone 4.5 mg once daily. Patients in this arm will also receive the investigating institution's current standard of care (described in detail in the "standard of care" arm) for patients with COVID-19. Colchicine 0.6 mg: Colchicine is an oral anti-inflammatory agent that is relatively inexpensive, readily available, and has been used for generations. Approved for treatment and prophylaxis of gout flares and Mediterranean fever, it is also used in a variety of other inflammatory conditions (e.g. pericarditis and diffuse vascular inflammation such as Behcet syndrome). Colchicine binds to tubulin causing depolymerization, which interferes with neutrophil chemotaxis, adhesion, and mobilization to sites of inflammation, and contributes to reduction in superoxide production; through interference of the NLRP3 inflammasome protein complex, colchicine inhibits IL-1b, IL-6, and IL-18 production. Naltrexone: Most well known as an opioid antagonist, or a treatment for alcohol dependence, naltrexone also possesses immunomodulatory effects. Seen exclusively at low doses, this attribute is being employed in the pain community as a novel anti-inflammatory agent.	Naltrexone-Only Arm n=35 Participants Patients randomized to an LDN-containing treatment arm (including the "combined arm") will receive naltrexone 4.5 mg once daily. The first dose can be given at any time during the day of enrollment/randomization, and will be timed at 08:00 daily thereafter (with AM colchicine dose, if in combined colchicine/LDN arm) for up to 28 days (unless new contraindication or exclusion criteria met). Patients in this arm will also receive the investigating institution's current standard of care (described in detail in the "standard of care" arm) for patients with COVID-19. Naltrexone: Most well known as an opioid antagonist, or a treatment for alcohol dependence, naltrexone also possesses immunomodulatory effects. Seen exclusively at low doses, this attribute is being employed in the pain community as a novel anti-inflammatory agent that has been shown to reduce symptom severity in fibromyalgia, Crohn's disease, multiple sclerosis, and complex regional pain syndrome. For this study, patients enrolled in a naltrexone-containing arm will take their daily dose of the medication (4.5mg) by oral suspension.	Standard of Care Arm n=35 Participants Patients in this arm will receive the investigating institution's current standard of care for patients with COVID-19. For example, all patients requiring supplemental oxygen (assuming no contraindications) would be candidates for both remdesivir 200 mg x 1 IV dose followed the next day by 100 mg q24h IV x up to 4 doses, as well as dexamethasone 6 mg q24h x 10 up to 10 doses.	Colchicine Group n=67 Participants All subjects who received Colchicine from being randomized into Colchicine-Only Arm or Colchicine and Naltrexone Combined Arm	No Colchicine Group n=70 Participants All subjects who did not receive Colchicine from being randomized into the Naltrexone-Only Arm and Standard of Care Arm	Naltrexone Group n=68 Participants All subjects who received Naltrexone from being randomized into Colchicine and Naltrexone Combined Arm or Naltrexone-Only Arm	No Naltrexone Group n=69 Participants All subjects who did not receive Naltrexone from being randomized into the Colchicine-Only Arm and Standard of Care Arm
In Patients Hospitalized With Moderate COVID-19, the Impact of Colchicine and LDN, Alone or in Combination, on Achieving Disease Recovery by Day 5.	22 Participants	24 Participants	20 Participants	18 Participants	46 Participants	38 Participants	44 Participants	40 Participants

SECONDARY outcome

Timeframe: Assessed from time of hospitalization until discharge, calculated after patient completes hospital stay - approximately 7 days on average

Study team will investigate the effects of colchicine and LDN, alone or in combination, on total amount of time (in days) patient spent in hospital from admission to discharge