Clinical trial NCT03455322: Norepinephrine Infusion Versus Midodrine & Octreotide in Patients With Hepatorenal Syndrome Type 1.
Official title: Pros & Cons of Norepinephrine Infusion Versus Midodrine & Octreotide in Patients With Hepatorenal Syndrome Type 1 in Intensive Care Unit.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Renal Impairment in Hepatorenal Syndrome
Lead sponsor: National Hepatology & Tropical Medicine Research Institute
Sponsor class: OTHER_GOV
First posted: 2018-03-06
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aimed to investigate the efficacy of midodrine plus octreotide versus norepinephrine and to determine the predictive factors of response in patients with HRS-AKI.

Detailed description: Both sexes aged 18 years or older having cirrhosis, ascites, and a diagnosis of HRS-AKI based on the 2015 International Club of Ascites (ICA) diagnostic criteria \[2\] were eligible for participation.

Screening and eligibility criteria were verified upon admission to the ICU. A diagnosis of AKI was established through comparing sCr value at time of ICU admission to that recorded in the patient's file. Patients who meet all other diagnostic criteria of HRS-AKI provided by the previous definition \[2\] were enrolled in the study. Qualified patients were subjected to baseline assessments after informed consent signature. It included vital sign measurements, presence of comorbidities, height and weight, Child-Pugh score and Sequential Organ Failure Assessment (SOFA) score. Vital signs, Blood urea nitrogen, sCr, serum sodium, serum albumin, total bilirubin, and complete blood count with differential were measured at baseline and at daily basis throughout the study period. Patients were randomized in a 1:1 ratio to receive either continuous infusion of norepinephrine in an initial dose of 0.5mg/h (Maximum 3 mg/h or oral midodrine 5mg three times/day (Maximum 12.5mg three times/day) plus octreotide 100μg/6h as subcutaneous injection (Maximum 200 μg/6h). Duration of treatment was allowed to extend to a maximum of 10 days. Administration of albumin at doses of 20 to 40 gm/day was recommended, as clinically indicated, for all patients in both study arms as per current ICA guidelines.

Eligibility criteria: Inclusion Criteria:

* All patients that will be included in the study have cirrhosis as diagnosed by clinical, biochemical, and ultrasound findings, with HRS type 1, the absence of bacterial infections; however, patients with bacterial infections could be included in the study if renal failure persisted after infection resolution by clinical, laboratory indices up to 48 hours.

Exclusion Criteria:

* Patients will be excluded if there are advanced cardiovascular diseases due to poor prognosis or any extrahepatic disease that could affect the short-term prognosis, the presence of advanced hepatocellular carcinoma or presence of contraindication to norepinephrine as hypotension due to blood volume deficits except emergency measure, mesenteric or peripheral vascular thrombosis unless there is life-saving procedure, profound hypoxia or hypercarbia.

Primary outcomes:
measure: the proportion of patients achieved full response
timeFrame: within10 days
Secondary outcomes:
measure: the proportion of patients achieved partial response
timeFrame: within 10 days
measure: Incidence of HRS reversal
timeFrame: within 10 days
measure: incidence of HRS-AKI relapse
timeFrame: 30 days
measure: overall survival
timeFrame: 30 days
measure: adverse events experienced throughout the study period in both treatment groups.
timeFrame: within 10 days
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: NHTMRI
Study officials:
References:
citation: El-Desoki Mahmoud EI, Abdelaziz DH, Abd-Elsalam S, Mansour NO. Norepinephrine is More Effective Than Midodrine/Octreotide in Patients With Hepatorenal Syndrome-Acute Kidney Injury: A Randomized Controlled Trial. Front Pharmacol. 2021 Jul 2;12:675948. doi: 10.3389/fphar.2021.675948. eCollection 2021.