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

• Status: Enrolling by invitation
• Trial end date: 2021-12-31
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to explore the impact of two medications-colchicine and low-dose naltrexone (LDN)-relative to standard of care (SOC) on COVID-19 disease progression to severe/critical illness and/or intubation in patients hospitalized with moderate COVID-19. As researchers have learned, COVID-19's clinical course suggests that the hyperinflammatory response seen in severe/critical cases is involved in the pathogenesis of associated adverse sequelae such as acute respiratory distress syndrome (ARDS), thromboembolic disease, and acute cardiac injury. Given colchicine has demonstrated clinical utility in inflammatory syndromes within these systems (e.g. endothelial/vascular/myocardial), and LDN acts both to boost the immune system, and limit an excessive response; they may prove useful in minimizing the risk of disease progression and associated adverse sequelae.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: HealthPartners Institute
• Collaborator: Park Nicollet Foundation
• Treatments: Colchicine; Naltrexone

Criteria

Inclusion Criteria:

1. Male and (non-pregnant, non-breastfeeding) females aged 18 years or older

2. Requiring admission to Methodist or Regions Hospital due to laboratory-confirmed COVID-19

3. Meets criteria of only up to moderate COVID-19 disease as defined by a clinical score of 2 or 3 at the time of enrollment, and one or more of the following:

1. Dyspnea limiting usual activities on baseline O2 needs

2. Respiratory rate >/= 30/min on O2 or room air

3. Blood oxygen saturations <94% on room air (or on baseline O2 needs if on supplemental oxygen prior to presentation at the hospital for a condition unrelated to COVID-19).

4. Requiring supplemental 02 above baseline needs (i.e. prior to presentation at hospital)

5. COVID-19 contributed to the current hospital admission, per attending provider's clinical assessment of the patient.

4. Ability to provide written informed consent, or has identifiable LAR that is able to do so on the patient's behalf as defined by study protocol, prior to performing study procedures.

Exclusion Criteria:

1. Patients meeting criteria for severe/critical COVID-19 as defined by study protocol or requiring O2 supplementation ≥10L nasal cannula at screening

2. Patients currently in shock as defined by hemodynamic instability requiring vasopressors

3. Patients with a current hospitalization for COVID-19 that is >/=7 days at the time of screening.

4. Clinical estimation of attending physician that the patient will require mechanical respiratory support within 48 hours of enrollment

5. Patients in which EITHER symptom onset OR a positive COVID-19 laboratory test occurred >14 days prior to enrollment.

6. Patients with concomitant influenza A or B at time of hospitalization if tested as part of ED/hospital admission.

7. Female patients who are pregnant or breastfeeding at time of hospital admission

8. Diagnosis of Chronic Kidney Disease stage ≥4 as documented in the patient's problem list (not based on CrCI calculations alone)

9. CrCl < 30 mL/min or requiring renal replacement therapy (e.g. intermittent hemodialysis, continuous renal replacement therapy, peritoneal dialysis) at screening

10. History of cirrhosis or advanced liver disease, or active hepatic viral infection

11. Transplant of kidney, lung, heart, or liver in the past 2 years

12. Uncontrolled severe gastrointestinal disorders, Crohn's disease, ulcerative colitis, chronic diarrhea, diarrhea predominant irritable bowel syndrome, active stomach or intestinal ulcer, or one that was treated within the last 6 months

13. Patients currently receiving agents that are p-glycoprotein AND strong CYP3A4 inhibitors with CrCl < 60 mL/min, or any combination of drug interactions that is not amenable to dosage adjustment (refer to list of medications with potential Colchicine and Naltrexone interactions).

14. Patients actively undergoing chemotherapy for an active malignancy, or history of a hematologic malignancies

15. Chronic or current use of colchicine or any mu-opioid antagonist.

16. Chronic, scheduled opioid therapy (i.e. not intermittent as needed use), or, prior to enrollment, an acute condition requiring continued pain control that is unattainable without ongoing opioid therapy.

17. Pre-existing condition that is being treated with tocilizumab, anakinra, sarilumab, other interleukin-antagonists, TNF-inhibitors, or JAK inhibitors.

18. NOTE: Patients treated with tocilizumab will be permitted to enroll if their care team is prescribing it for COVID-19. Use of tocilizumab at baseline for another indication will continue to be excluded.

19. Participation in any other clinical trial of an experimental treatment for COVID-19, note:

1. While convalescent plasma is no longer recommended within HP, it can be given if deemed appropriate by the medical team once ≥ 24 hours has elapsed since enrollment;

2. Patients previously enrolled in the C3PO study can enroll in this study, as any convalescent plasma received would have been outpatient;

3. Remdesivir is allowed per standard protocol;

4. Dexamethasone is allowed per standard protocol

20. Patients actively enrolled in hospice or that are DNI or on palliative care

21. History of hypersensitivity reaction to colchicine or its inactive ingredients

22. History of hypersensitivity reaction to naltrexone or its inactive ingredients

23. Incarcerated or a ward of the state

24. Any patient considered an unsuitable candidate, for any reason, by study investigators.