Clinical trial NCT05453214: Mineralocorticoid Use in COVID-19 Patients
Official title: Safety and Efficacy of Fludrocortisone Addition to Dexamethasone in the Management of Hospitalised COVID-19 Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
ARDS
Keywords: fludrocortisone
mineralocorticoid
COVID-19
ARDS
Aldosterone
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2022-07-12
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time to recovery
timeFrame: 28 days
Secondary outcomes:
measure: Mortality Rate
timeFrame: 28 days
measure: Length of hospital stay
timeFrame: 28 days
measure: Rate of ICU admission
timeFrame: 28 days
measure: Mechanical ventilation need
timeFrame: 28 days
measure: Improvement of lymphopenia
timeFrame: 7 days
measure: Duration of Increased Supplemental Oxygen
timeFrame: 28 days
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Ain Shams University
state: Abbasia
Study officials:
affiliation: Alazhar allergy and immunology center
name: Muhammad S Zeafan
role: PRINCIPAL_INVESTIGATOR
References:
citation: Coto E, Avanzas P, Gomez 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.
citation: Bauer JH. Age-related changes in the renin-aldosterone system. Physiological effects and clinical implications. Drugs Aging. 1993 May-Jun;3(3):238-45. doi: 10.2165/00002512-199303030-00005.
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.
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.
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. doi: 10.1097/00000441-198605000-00006.