Methylene Blue Versus Vasopressin Analogue for Treatment of Septic Shock in Preterm Neonate

Study Overview
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Brief Summary
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A randomized, prospective study comparing methylene blue versus terlipressin in treatment of catecholamines resistant shock in preterm neonate

Detailed Description
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The study will be an un-blinded, Phase 2, randomized, 1:1, prospective trial comparing methylene blue versus terlipressin in treatment of preterm neonate with catecholamines resistant septic shock the outcome as regard elevation of mean arterial blood pressure will be measured within 72 hours

Official Title
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Methylene Blue Versus Vasopressin Analogue for Treatment of Septic Shock in Preterm Neonate

Conditions
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Neonatal Sepsis, Refractory Shock

Intervention / Treatment
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* Drug: Methylene Blue


Participation Criteria
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Eligibility Criteria
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Neonate with Gestational age at birth ≤ 36weeks Inclusion Criteria: diagnosis of Septic shock according to clinical sepsis score of Tollner and Hematologic Scoring System of Rodwell Refractory septic shock defined as hypotension although adequate fluid resuscitate and high dose vasopressor(NE >0.5 mcg/kg/min) consent form Exclusion Criteria: known case of G6pd deficiency Hx of drug allergy MB, NE, terlipressin Patients with severely impaired renal function. History of maternal drug intake of selective serotonin reuptake inhibitors,and Serotonin-Norepinephrine Reuptake Inhibitors
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Methylene Blue group (Group MB)<br>Methylene Blue is supplied in 1 ml or 10 mL single-dose ampules. Each 1 mL ampule contains 10 mg of methylene blue as a clear dark blue solution Any unused product or waste material should be disposed of in accordance with local practice, For administration to be diluted before use in a solution of 50 mL 5% Dextrose in Water (D5W) in order to avoid local pain, particularly in the paediatric population. Use the diluted solution immediately after preparation. Do not mix with sodium chloride 9 mg/mL (0.9%) solution for injection, because it has been demonstrated that chloride reduces the solubility of methylene blue. | Drug: Methylene Blue<br>* Methylene Blue group (Group MB):will receive IV MB initiated with a first loading dose ( 1 mg/kg over 30 minutes ) then continuous IV infusion( 0.15 mg/kg per hour for up to 24 hours) Terlipressin Group (Group TP) Terlipressin will be initiated with a loading dose ( 2 μg/kg intravenous over 30 minutes ) followed by continuous IV infusion starting by 2 μg/kg/h escalating up every 15 minutes up to 20 μg/kg/h<br>* Other names: terlipressin acetate;|
| Placebo Comparator: Terlipressin Group (Group TP )<br>The active substance is terlipressin acetate. Each ampoule contains 1 mg of terlipressin acetate in 8.5 ml solution for injection. This is equivalent to 0.12 mg terlipressin acetate per ml. The powder is to be dissolved in the enclosed solvent and slowly administered intravenously. Further dilution up to 10 ml with sterile isotonic sodium chloride solution is possible. Store in a refrigerator at 2-8˚C. Keep the ampoules in the outer carton in order to protect from light | Drug: Methylene Blue<br>* Methylene Blue group (Group MB):will receive IV MB initiated with a first loading dose ( 1 mg/kg over 30 minutes ) then continuous IV infusion( 0.15 mg/kg per hour for up to 24 hours) Terlipressin Group (Group TP) Terlipressin will be initiated with a loading dose ( 2 μg/kg intravenous over 30 minutes ) followed by continuous IV infusion starting by 2 μg/kg/h escalating up every 15 minutes up to 20 μg/kg/h<br>* Other names: terlipressin acetate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to assess the efficancy of each intervention in improving hemodymaic status: time taken to reach adequate mean blood pressure | The time taken to reach adequate mean blood pressure Reduction in the dosage of the standard inotropic support | 24hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to assess the effect of intervention on survival | mortality rate | 4 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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methylene blue, terlipressin, septic shock, preterm neonate