Mineralocorticoid Use in COVID-19 Patients

COVID-19 Clinical Trial

Official title:

Safety and Efficacy of Fludrocortisone Addition to Dexamethasone in the Management of Hospitalised COVID-19 Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05453214
• Other study ID #: FMASU R111c/2021
• Status: Completed
• Phase: Phase 3
• Start date: December 4, 2021
• Est. completion date: June 20, 2022

Study information

• Verified date: July 2022
• Source: Ain Shams University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

There is a considerable variability in aldosterone levels between individuals, and this may explain the wide variability in disease severity among those infected so we designed a pilot study to test for the safety and efficacy of fludrocortisone addition to standard of care in hospitalised COVID-19 patients.

Description:

Many studies have shown involvement of renin-angiotensin-aldosterone system (RAAS) in pathophysiology of COVID-19. There is a considerable variability between people infected with SARS-COV-2 virus in terms of severity. At pathophysiological level there are variable degrees of increased capillary permeability with resultant fluid leak. We hypothesize that the physiological response to overcome this fluid leak mainly involves stimulation of mineralocorticoid (aldosterone) pathway. Hence; those with defective mineralocorticoid response are at high risk for disease complications. Aldosterone secretion capacity is affected by many factors whether physiological (age, sex, ethnicity and pregnancy) or pathological (e.g. smoking); this is reflected in wide differences (regarding aldosterone levels) between groups of people depending on these factors. These variations in mineralocorticoid capacity between groups of people may explain why some certain groups are at high risk for severe disease while others are at a lower risk. So we designed this pilot study to assess safety and efficacy of mineralocorticoid, in the form of fludrocortisone, as a potential treatment for COVID-19 by its addition to dexamethasone in hospitalized COVID-19 patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: June 20, 2022
• Est. primary completion date: March 3, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male and non-pregnant female patients 18 years of age or older
• Diagnosed with COVID-19 pneumonia as per local guidelines
• Oxygen saturation (SaO2) of 93 % or less while they were breathing ambient air.

Exclusion Criteria:

• A physician decision that involvement in the trial will not be in the patient's best interest, presence of any condition that would not allow the protocol to be followed safely.
• known allergy or hypersensitivity to fludrocortisone.
• known severe liver or kidney disease, uncontrolled hypertension, diabetes mellitus and peptic ulcer disease.
• Hypokalemia (serum potassium of less than 3.5 mEq/L)
• Use of medications that are contraindicated with fludrocortisone and that could not be replaced or stopped during the trial period.

Related Conditions & MeSH terms

• ARDS
• COVID-19

Intervention

Drug:
• Fludrocortisone Acetate 0.1 MG
Fludrocortisone acetate 0.1 mg tablet / 12 hours; dose to be titrated according to response.

Locations

Country	Name	City	State
Egypt	Ain Shams University	Cairo	Abbasia

Sponsors (1)

Lead Sponsor	Collaborator
Ain Shams University

Country where clinical trial is conducted

Egypt, 

References & Publications (5)

Bauer JH. Age-related changes in the renin-aldosterone system. Physiological effects and clinical implications. Drugs Aging. 1993 May-Jun;3(3):238-45. Review. — View Citation

Coto E, Avanzas P, Gómez J. The Renin-Angiotensin-Aldosterone System and Coronavirus Disease 2019. Eur Cardiol. 2021 Mar 9;16:e07. doi: 10.15420/ecr.2020.30. eCollection 2021 Feb. Review. — View Citation

Gossain VV, Sherma NK, Srivastava L, Michelakis AM, Rovner DR. Hormonal effects of smoking--I: Effects on plasma renin activity. Am J Med Sci. 1986 May;291(5):321-4. — View Citation

Szymanski P, Klisiewicz A, Lubiszewska B, Lipczynska M, Kowalski M, Janas J, Hoffman P. Gender differences in angiotensin II and aldosterone secretion in patients with pressure overloaded systemic right ventricles are similar to those observed in systemic arterial hypertension. Int J Cardiol. 2011 Mar 17;147(3):366-70. doi: 10.1016/j.ijcard.2009.09.535. Epub 2009 Nov 7. — View Citation

Wang W, Tang J, Wei F. Updated understanding of the outbreak of 2019 novel coronavirus (2019-nCoV) in Wuhan, China. J Med Virol. 2020 Apr;92(4):441-447. doi: 10.1002/jmv.25689. Epub 2020 Feb 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to recovery	The first day, during the 28 days after enrollment, on which a patient met the criteria for category 1 or 2 on the eight-category ordinal scale	28 days
Secondary	Mortality Rate	All-cause mortality rate over 28 days post enrollment.	28 days
Secondary	Length of hospital stay	Number of days since enrollment till hospital discharge.	28 days
Secondary	Rate of ICU admission	Number of patients who experienced worsening of clinical status necessitating ICU admission.	28 days
Secondary	Mechanical ventilation need	Number of patients who needed invasive mechanical ventilation during hospitalisation.	28 days
Secondary	Improvement of lymphopenia	Reversal of lymphopenia - measured at days 3 and 7 after initiation of treatment.	7 days
Secondary	Duration of Increased Supplemental Oxygen	Number of days counted from enrollment over which the participant requires supplemental oxygen in excess over his/her baseline.	28 days