NCT04492280

Evaluation of the Role of Hydrocortisone Either Alone or Combined With Fludrocortisone in the Outcome of Septic Shock in Adults

Completed Phase 4 Last updated 30 July 2020

What this trial tests

Phase 4 trial testing Hydrocortisone in Septic Shock in 66 participants. Completed in 1 September 2019.

Timeline

1 September 2018

Primary endpoint
1 September 2019

1 September 2019

Quick facts

Lead sponsor	Ain Shams University
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	prevention
Enrollment	66
Start date	1 September 2018
Primary completion	1 September 2019
Estimated completion	1 September 2019
Sites	1 location across Egypt

Drugs / interventions tested

• Hydrocortisone (hydrocortisone) — full drug profile →

Conditions studied

• Septic Shock — all drugs for Septic Shock →

Sponsor

Ain Shams University

Who can join

Adults 18 to 80, any sex, with Septic Shock. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

During Infection, oflfending microbes interact with the host immune system producing a downstream inflammatory cascade involving cytokines and other mediators, which in turn triggers a systemic response. The resultant effects linclude vasodilation, increased vascular permeability, myocardial depression, and impairment of the coagulation cascade, resulting in global imbalance of systemic oxygen supply and demand. During the late stage of sepsis, immunosuppression predominates, leading to multi-organ dysfunction and further clinical deterioration .

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection with two or three on Quick Sepsis-related organ failure assessment score (qSOFA). Septic shock is defined as the presence of sepsis and refractory hypotension to fluid management. Vasopressors are needed to maintain systolic blood pressure more than 90mmHg or mean blood pressure more than 65 mmHg .

Experimental and Clinical evidence suggests that sepsis is associated with dysregulated response of Hypothalamic-pituitary-adrenal axis that may involve any of the steps from cortisol production to cortisol use by cells .

Glucocorticoid therapy for the treatment of septic shock remains controversial, with conflicting evidence regarding a mortality benefit. It has been used in patients with septic shock who remained hypotensive after fluid and vasopressor resuscitation.

Fludrocortisone is a corticosteroid and acts as a powerful mineralocorticoid along with some additional but comparatively very weak glucocorticoid activity. Relative to cortisol, it is to 10 times the glucocorticoid potency but 250 to 800 times the mineralocorticoid potency .

Fludrocortisone is added to hydrocortisone to provide additional mineralocorticoid potency. The rationale for adding mineralocorticoid treatment is that an experimental sepsis study showed marked nuclear factor NF-κB mediated down regulation of vascular mineralocorticoid receptors .

Corticosteroids attenuate inflammation in various organs an effect partly related to inhibition of nuclear factor NF-κB. Improve cardiovascular function by restoring effective blood volume through increased mineralocorticoid activity and by increasing systemic vascular resistance through vascular α-Adrenergic responsiveness and reduces inflammation-mediated vasodilation .

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Effectiveness of Fludrocortisone Plus Hydrocortisone versus Hydrocortisone Alone in Septic Shock: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.
   Teja B, Berube M, Pereira TV, Law AC, et al · · 2024 · cited 30× · PMID 38271488 · DOI 10.1164/rccm.202310-1785oc
2. Corticosteroids for treating sepsis in children and adults.
   Annane D, Briegel J, Granton D, Bellissant E, et al · · 2025 · cited 7× · PMID 40470636 · DOI 10.1002/14651858.cd002243.pub5