Anabolic Steroid and Propranolol in Paediatric Burn

Role of Anabolic Steroid and Propranolol in Paediatric Burn- A Randomized Controlled Trial

propranolol and anabolic steroids have a role in pediatric burn patients and their combined effects are to be studied here. They decrease the catabolic response to burn trauma and minimize the duration of growth arrest hence improving the outcome

Study Overview

• Status: Recruiting
• Conditions: Development; Growth; Bone; Arrest
• Intervention / Treatment: Drug: Propranolol; Drug: Nandrolone Decanoate

Detailed Description

Burn is a major cause of morbidity and mortality worldwide; rate being seven times higher in low- and middle- income countries than high income countries. According to WHO, worldwide 11million people require medical attention secondary to burns. In Pakistan, 17% of burn patients have temporary disability while 18% suffer from a permanent disability Various studies have been done to improve patient outcome in terms of morbidity and mortality. Different medical interventions seem to have promising role in improving patient outcome in burn population.

Majority of pathological problems are due to catecholamines, an integral part of systemic metabolic drive, which increase approximately 10-fold as a response to injury . Hypermetabolic state has two aspects-the "ebb" and "flow" phases. The "ebb" phase lasts till first 48hours and has decreased metabolic rate and oxygen consumption while "flow" phase, which starts after resuscitation and has huge metabolic turnover, is the problematic one and needs intervention to decrease grave outcomes on patient's health. Systemic effects of catecholamines are significant once burned surface area increases more than 20% of the TBSA and persist for years . Various studies show that Propranolol and Oxandrolone have beneficial effects on decreasing morbidity and mortality in burn population Propranolol, a non-selective beta adrenergic blocker, has been used to minimize systemic effects of catecholamines and hypothetically results in anti-catabolic effects especially when given during ebb phase of the process i.e. decreases heart rate (HR) and blood pressure (BP) while during flow phase it increases hematocrit levels by increasing the renal erythropoietin secretion and decreases number of transfusions as well as blood loss during skin grafting "Herndon et al demonstrated that the cardiac effort was significantly reduced by 20% to 36% when the patients were given 2 mg/kg every 24 hours for 5 days. They determined that an ideal dose of 0.5 to 1.0 mg/kg intravenously every 6 to 8 hours should be given to adequately reduce left ventricular work without adversely affecting oxygen delivery or other cardiac functions" In another study done by Minifee et al, propranolol does not affect overall body delivery and consumption of oxygen but significantly decreases cardiac muscle requirement of oxygen . Moreover hyper-/hypo-glycemia, hypotension, azotemia, hypothermia, arrythmias and peripheral ischemia are also not observed as adverse effects . Another study by Baron et al showed that prolonged administration of oral or IV propranolol does not have an adverse effect on morbidity or mortality

Anabolic steroid (Oxandrolone/nandrolone) has a definite role in building up body's protein stores. Unlike testosterone, its adverse effects, acne, hirsutism, behavioral changes and liver functions are not documented, so they are considered safe. Use of oxandrolone alone and in combination with propranolol has a definitive effect as anti-catabolic agent and helps in better recovery and long-term outcomes on child's growth and decreases cardiac load.

A study done by Sylvia Ojeda et al at university of Texan in 2018 showed that propranolol is both safe and effective in managing the cardiovascular effects of hypermetabolic state in burn patients. A couple of other studies show that both propranolol and oxandrolone have a role in reducing the burden of disease in burn but data is lacking on effects of administration of both the drugs combined. Moreover, how the medication will affect our population is yet to be determined. This study will help us compare the effects of both drugs in our population and decrease the morbidity and mortality in burn patients.

• Study Type: Interventional
• Enrollment (Anticipated): 114
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Azwa Janjua; Phone Number: 03326223344; Email: azwamunim@gmail.com

Study Locations

• Pakistan
  • Punjab
    • Lahore, Punjab, Pakistan, 54000
      • Recruiting
      • King Edward Medical University, Mayo Hospital
      • Contact: Azwa Janjua; Phone Number: 03326223344; Email: azwamunim@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 12 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients presenting within 48 hours of burn
• more than 20% and less than 40 %of TBSA burn (measured via modified rule of nine for pediatric burn according to age)
• age 2-12 years (as safety of anabolic steroids is not established in <2years of age)
• Scald and flame burn

Exclusion Criteria:

• Diabetics (diagnosed before hospital admission)
• Renal disease (diagnosed before hospital admission)
• Asthmatics (on medication previously)
• Cardiac anomalies (previously diagnosed)
• Patients requiring cardiac support (norepinephrine, dobutamine at any dose and dopamine >7ug/kg).
• All 4 limbs burnt

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Propranolol will be given to this group	Drug: Propranolol; 2mg/kg/day in 3-4 dividd doses
Experimental: group b; steroid will be given	Drug: Nandrolone Decanoate; 1mg/kg weekly
Experimental: group c; both propranolol and steroids will be given	Drug: Propranolol; 2mg/kg/day in 3-4 dividd doses; Drug: Nandrolone Decanoate; 1mg/kg weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
reversal of growth arrest	BMI in kg/m^2	at 1 year after burn
Bone mineral density measure	Bone mineral density as g/cm^2 (Z-score)	at 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
no of blood transfusions	number of blood transfusions during hospital stay	at 60 days

Collaborators and Investigators

• Sponsor: King Edward Medical University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Anticipated): September 28, 2023
• Study Completion (Anticipated): September 28, 2023

Study Registration Dates

• First Submitted: January 26, 2021
• First Submitted That Met QC Criteria: March 27, 2023
• First Posted (Actual): April 10, 2023

Study Record Updates

• Last Update Posted (Actual): April 10, 2023
• Last Update Submitted That Met QC Criteria: March 27, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Pediatric; Growth; Steroid; Propranolol; Burn; arrest
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Bone Density Conservation Agents; Androgens; Anabolic Agents; Propranolol; Nandrolone; Nandrolone Decanoate; Nandrolone phenpropionate
• Other Study ID Numbers: 126/RC/KEMU

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No