Dobutamine Versus Milrinone in Management of Critically Ill Low Cardiac Output Pediatric Patients at Cairo University Children's Hospital

NCT ID: NCT05999487

Last Updated: 2023-08-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-10-31

Study Completion Date

2024-05-31

Brief Summary

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The aim of the study is to detect wither dobutamine or milrinone have a privilege in the management of low cardiac output pediatric patients over the other.

Detailed Description

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Randomized controlled trials (RCTs) enrolling critically ill patients with low cardiac output syndrome (LCOS) admitted at pediatrics emergency and intensive care units ,Cairo University Children's Hospital, identified by treating medical team as requiring initiation of inotropic therapy based on healthcare team assessment of :

* Capillary refill time \> 3 sec
* Hypotension (less than the 5th percentile or less than 90/50 mmHg for children 10 years or older (Kleinman et al.,2010) (Haque et al .,2007)
* Oliguria (urine output that is less than 1 mL/kg/h in infants, less than 0.5 mL/kg/h in children ) (Nakano et al.,2022)
* Metabolic acidosis with base excess \> -2 (Nakano et al.,2020)

Patient randomization will be done by a computer based generation , serial enveloped numbers will be taken for the patients. Cardiac assessment will be done by a blinded pediatric cardiologist. If at any time the randomly assigned therapy considered to be failed or unsafe to continue, the treating physician will discontinue randomization and will continue with the appropriate medication according to the patients need.

Every patient will be evaluated after the first 24 hours of starting the inotropic therapy by :

* pre and post inotropic therapy ICON measurements ( evaluating cardiac index and systemic vascular resistance pre and post inotropic support)
* pre and post inotropic therapy echocardiography ( evaluating systolic and diastolic dysfunction by M-mode and two dimensional methods) through measuring LV EDD cm, LV ESD cm, LV EDV ml, LVESV ml, FS% , LV mass, EF% , MAPSE cm, TAPSE cm.
* pre and post inotropic therapy clinical assessment of vital signs (heart rate , blood pressure, capillary refill time and urine output as mention before)
* The need of titration up of inotropes :

Milrinone will start by 0.25 , 0.5 , 0.75 we can titrate up with time interval 3 hours after re-assessment.

Dobutamine will start by 5, 10 , 15, 20 we can titrate with time interval 15 mins after re-assesment.

-Time to achievement of therapeutic endpoints for hemodynamics

* adequate blood pressure
* clinically adequate cardiac output ( capillary refill time \< 2sec , urine output that is more than 1 mL/kg/h in infants, more than 0.5 mL/kg/h in children, full conscious )

Data will be collected for each patient in form of \[ Time Frame: Through first 24 hours up to first week since admission \] :

1. Total time on inotropes (in hours)
2. Non-invasive or invasive mechanical ventilation Total number of days requiring non-invasive or invasive mechanical ventilation
3. Change in cardiac index (\[CI\] measured with ICON
4. Change in systemic vascular resistance \[SVR\] measured with ICON
5. Presence of acute kidney injury (defined as an increase in serum creatinine or a decrease in urine output or both over hours to days.) (Jacob J et al.,2020)
6. Absence of metabolic acidosis (BE -2 to 2)
7. Arrhythmia requiring medical team intervention, either through electrical or chemical cardioversion or any intravenous anti-arrhythmia medication administration
8. Need for up-titration or addition of new vasopressor therapy

Conditions

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Dobutamine, Milrinone , Pediatrics , Low Cardiac Output

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Investigators
. Cardiac assessment will be done by a blinded pediatric cardiologist.

Study Groups

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patients who will recieve dobutrex

patient presenting with acute heart failure , who will recieve dobutrex as a result of their randomixation , startng dose will be 5 mic , assesing their need for tittration of dose , the need for addition of another inotrope , the prescence of any side effects and the duration of inotropic use for reaching hemodynamically stable state

Group Type ACTIVE_COMPARATOR

Dobutamine

Intervention Type DRUG

Patient randomization will be done by a computer based generation , serial enveloped numbers will be taken for the patients. Cardiac assessment will be done by a blinded pediatric cardiologist. If at any time the randomly assigned therapy considered to be failed or unsafe to continue, the treating physician will discontinue randomization and will continue with the appropriate medication according to the patients need.

Milrinone will start by 0.25 , 0.5 , 0.75 we can titrate up with time interval 3 hours after re-assessment.

Dobutamine will start by 5, 10 , 15, 20 we can titrate with time interval 15 mins after re-assesment.

patients who will recieve milirinone

patient presenting with acute heart failure , who will recieve milirinone as a result of their randomixation , startng dose will be 0.25 mic , assesing their need for tittration of dose , the need for addition of another inotrope , the prescence of any side effects and the duration of inotropic use for reaching hemodynamically stable state

Group Type EXPERIMENTAL

Dobutamine

Intervention Type DRUG

Patient randomization will be done by a computer based generation , serial enveloped numbers will be taken for the patients. Cardiac assessment will be done by a blinded pediatric cardiologist. If at any time the randomly assigned therapy considered to be failed or unsafe to continue, the treating physician will discontinue randomization and will continue with the appropriate medication according to the patients need.

Milrinone will start by 0.25 , 0.5 , 0.75 we can titrate up with time interval 3 hours after re-assessment.

Dobutamine will start by 5, 10 , 15, 20 we can titrate with time interval 15 mins after re-assesment.

Interventions

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Dobutamine

Patient randomization will be done by a computer based generation , serial enveloped numbers will be taken for the patients. Cardiac assessment will be done by a blinded pediatric cardiologist. If at any time the randomly assigned therapy considered to be failed or unsafe to continue, the treating physician will discontinue randomization and will continue with the appropriate medication according to the patients need.

Milrinone will start by 0.25 , 0.5 , 0.75 we can titrate up with time interval 3 hours after re-assessment.

Dobutamine will start by 5, 10 , 15, 20 we can titrate with time interval 15 mins after re-assesment.

Intervention Type DRUG

Other Intervention Names

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milrinone

Eligibility Criteria

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Inclusion Criteria

* 1-Patients from age of 1 month to 14 years old of both sexes.

2-Patients presenting with fluid refractory shock with low cardiac output state, evidenced by sustained hypotension (systolic blood pressure below 5th percentile for age) and end organ dysfunction (altered level of consciousness, renal or hepatic dysfunction)

3-Clinical evidence of systemic and/or pulmonary congestion despite use of vasodilators and/or diuretics

4-Refractory heart failure requiring admission for inotropic support.

Exclusion Criteria

1-All other causes of pediatric shock not in need for inotropic support (eg.isolated hypovolemic shock, anaphylaxis,….)

2 - patients not fit for randomization needing specific line of management (eg. Sever hypotension patients with good filling pressure unfit for milrinone , patients previously known having sever pulmonary hypertension not fit for dobutamine ,…)

3-post cardiac surgery patients with low cardiac output manifestation.
Minimum Eligible Age

1 Month

Maximum Eligible Age

14 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cairo University

OTHER

Sponsor Role lead

Responsible Party

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Nada Gamal

pediatric resident

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Cairo University Children'S Hospital

Giza, , Egypt

Site Status

Countries

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Egypt

Central Contacts

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nada gamal

Role: CONTACT

01062094645

Hafez Bazraa, professor

Role: CONTACT

01222235316

References

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Haque IU, Zaritsky AL. Analysis of the evidence for the lower limit of systolic and mean arterial pressure in children. Pediatr Crit Care Med. 2007 Mar;8(2):138-44. doi: 10.1097/01.PCC.0000257039.32593.DC.

Reference Type BACKGROUND
PMID: 17273118 (View on PubMed)

Jacob J, Dannenhoffer J, Rutter A. Acute Kidney Injury. Prim Care. 2020 Dec;47(4):571-584. doi: 10.1016/j.pop.2020.08.008. Epub 2020 Oct 1.

Reference Type BACKGROUND
PMID: 33121629 (View on PubMed)

Jentzer JC, Coons JC, Link CB, Schmidhofer M. Pharmacotherapy update on the use of vasopressors and inotropes in the intensive care unit. J Cardiovasc Pharmacol Ther. 2015 May;20(3):249-60. doi: 10.1177/1074248414559838. Epub 2014 Nov 28.

Reference Type BACKGROUND
PMID: 25432872 (View on PubMed)

Kleinman ME, Chameides L, Schexnayder SM, Samson RA, Hazinski MF, Atkins DL, Berg MD, de Caen AR, Fink EL, Freid EB, Hickey RW, Marino BS, Nadkarni VM, Proctor LT, Qureshi FA, Sartorelli K, Topjian A, van der Jagt EW, Zaritsky AL; American Heart Association. Pediatric advanced life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Pediatrics. 2010 Nov;126(5):e1361-99. doi: 10.1542/peds.2010-2972D. Epub 2010 Oct 18. No abstract available.

Reference Type BACKGROUND
PMID: 20956434 (View on PubMed)

Lewis TC, Aberle C, Altshuler D, Piper GL, Papadopoulos J. Comparative Effectiveness and Safety Between Milrinone or Dobutamine as Initial Inotrope Therapy in Cardiogenic Shock. J Cardiovasc Pharmacol Ther. 2019 Mar;24(2):130-138. doi: 10.1177/1074248418797357. Epub 2018 Sep 2.

Reference Type BACKGROUND
PMID: 30175599 (View on PubMed)

Mathew R, Di Santo P, Jung RG, Marbach JA, Hutson J, Simard T, Ramirez FD, Harnett DT, Merdad A, Almufleh A, Weng W, Abdel-Razek O, Fernando SM, Kyeremanteng K, Bernick J, Wells GA, Chan V, Froeschl M, Labinaz M, Le May MR, Russo JJ, Hibbert B. Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock. N Engl J Med. 2021 Aug 5;385(6):516-525. doi: 10.1056/NEJMoa2026845.

Reference Type BACKGROUND
PMID: 34347952 (View on PubMed)

Masse L, Antonacci M. Low cardiac output syndrome: identification and management. Crit Care Nurs Clin North Am. 2005 Dec;17(4):375-83, x. doi: 10.1016/j.ccell.2005.07.005.

Reference Type BACKGROUND
PMID: 16344207 (View on PubMed)

Nakano H, Nagai T, Honda Y, Honda S, Iwakami N, Matsumoto C, Asaumi Y, Aiba T, Noguchi T, Kusano K, Yokoyama H, Ogawa H, Yasuda S, Chikamori T, Anzai T. Prognostic value of base excess as indicator of acid-base balance in acute heart failure. Eur Heart J Acute Cardiovasc Care. 2020 Aug;9(5):399-405. doi: 10.1177/2048872619898781. Epub 2020 Jan 23.

Reference Type BACKGROUND
PMID: 31970993 (View on PubMed)

Nakano H. Oliguria. https://emedicine.medscape.com/article/983156-overview. Updated: Feb 28, 2022. Accessed at 15-12-2022.

Reference Type BACKGROUND

Uhlig K, Efremov L, Tongers J, Frantz S, Mikolajczyk R, Sedding D, Schumann J. Inotropic agents and vasodilator strategies for the treatment of cardiogenic shock or low cardiac output syndrome. Cochrane Database Syst Rev. 2020 Nov 5;11(11):CD009669. doi: 10.1002/14651858.CD009669.pub4.

Reference Type BACKGROUND
PMID: 33152122 (View on PubMed)

Other Identifiers

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inotropes in pediatrics

Identifier Type: -

Identifier Source: org_study_id

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