Safety and Efficacy of Midodrine Hydrochloride in the Management of Refractory Ascites Due to Cirrhosis in Children

NCT04043858 | Unknown

• 1 other identifier: Mid-Asci-Ped
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Ascites in liver cirrhosis is explained by increased production of vasoactive substances leading to renal vasoconstriction and salt and water retention. The retained water then accumulates in the peritoneal cavity under the effect of portal hypertension and low albumin. Refractory ascites is defined as ascites that cannot be mobilized or prevented from early recurrence after large-volume paracentesis despite medical therapy and dietary sodium restriction. Midodrine is an α1 receptor agonist that can improve systemic and renal hemodynamics in non-azotemic cirrhotic patients by counteracting mesenteric vasodilatation, which is accentuated in cirrhosis.

Conditions

Refractory Ascites; Children, Only

Outcome Measures

Primary Outcomes (7)

• Side effect no 1

  number of patients with Elevated BP: ≥90th percentile to \<95th percentile

  3 months

• Side effect no 2

  number of patients with Stage 1 HTN: ≥95th percentile to \<95th percentile + 12 mmHg or 130/80 to 139/89 mm Hg (whichever is lower)

  3 months

• Side effect no 3

  number of patients with Stage 2 HTN: ≥95th percentile + 12 mm Hg or ≥140/90 mm Hg (whichever is lower) mmHg or 130/80 to 139/89 mm Hg (whichever is lower)

  3 months

• Side effect no 4

  number of patients with low heart rate

  3 months

• Side effect no 5

  number of patients with urine retention

  3 months

• Side effect no 6

  number of patients with severe itching

  3 months

• Side effect no 7

  number of patients with skin rash

  3 months

Secondary Outcomes (3)

• Complete Response

  12 months

• Partial response

  12 months

• non-response

  3 months

Study Arms (1)

Midodrine daily

EXPERIMENTAL

Midodrine hydrochloride 2.5 mg tab once per day

Drug: Midodrine 2.5 mg tab

Interventions

Midodrine 2.5 mg tab DRUG

Patients receive an oral daily dose of 2.5 mg midodrine if age 7-12 years and receive 2.5 mg twice daily of more than 12 years

Also known as: ProAmatine

Midodrine daily

Eligibility Criteria

• Age: 7 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Children aged 7-18 years
• Both sexes
• Having refractory ascites (not responding to maximal dose of diuretics
• Diuretic-induced complications necessitate discontinuation of the drug

You may not qualify if:

• Non-cirrhotic causes of ascites
• Intrinsic renal disease ( e.g; polycystic kidney disease)
• Active gastrointestinal bleeding or the presence of risky varices
• Patients with Portal vein thrombosis and Budd-Chiari
• Cardiovascular disease
• Systemic hypertension or prehypertension
• Hyperthyroidism
• Patients with narrow-angle glucoma

Sponsors & Collaborators

• National Liver Institute, Egypt: lead

Study Sites (1)

Pediatric Hepatology, Gastroenterology and Nutrition Department, National Liver Institute, Menoufia University

Shibīn al Kawm, Menofiya, 32511, Egypt

RECRUITING

Related Publications (12)

• Albillos A, Banares R, Gonzalez M, Catalina MV, Molinero LM. A meta-analysis of transjugular intrahepatic portosystemic shunt versus paracentesis for refractory ascites. J Hepatol. 2005 Dec;43(6):990-6. doi: 10.1016/j.jhep.2005.06.005. Epub 2005 Jul 5.

  PMID: 16139922 BACKGROUND

• Bes DF, Cristina Fernandez M, Malla I, Repetto HA, Buamscha D, Lopez S, Martinitto R, Cuarterolo M, Alvarez F. Management of cirrhotic ascites in children: Review and recommendations. Part 2: Electrolyte disturbances, nonelectrolyte disturbances, therapeutic options. Arch Argent Pediatr. 2017 Oct 1;115(5):505-511. doi: 10.5546/aap.2017.eng.505. English, Spanish.

  PMID: 28895701 BACKGROUND

• Cardenas A, Arroyo V. Refractory ascites. Dig Dis. 2005;23(1):30-8. doi: 10.1159/000084723.

  PMID: 15920323 BACKGROUND

• Chen L, Wang L, Sun J, Qin J, Tang C, Jin H, Du J. Midodrine hydrochloride is effective in the treatment of children with postural orthostatic tachycardia syndrome. Circ J. 2011;75(4):927-31. doi: 10.1253/circj.cj-10-0514. Epub 2011 Feb 2.

  PMID: 21301135 BACKGROUND

• Dionne JM. Updated Guideline May Improve the Recognition and Diagnosis of Hypertension in Children and Adolescents; Review of the 2017 AAP Blood Pressure Clinical Practice Guideline. Curr Hypertens Rep. 2017 Oct 16;19(10):84. doi: 10.1007/s11906-017-0780-8.

  PMID: 29035421 BACKGROUND

• JCS Joint Working Group. Guidelines for drug therapy in pediatric patients with cardiovascular diseases (JCS 2012). Digest version. Circ J. 2014;78(2):507-33. doi: 10.1253/circj.cj-66-0083. Epub 2013 Dec 26. No abstract available.

  PMID: 24369273 BACKGROUND

• Hanafy AS, Hassaneen AM. Rifaximin and midodrine improve clinical outcome in refractory ascites including renal function, weight loss, and short-term survival. Eur J Gastroenterol Hepatol. 2016 Dec;28(12):1455-1461. doi: 10.1097/MEG.0000000000000743.

  PMID: 27622998 BACKGROUND

• Baker-Smith CM, Flinn SK, Flynn JT, Kaelber DC, Blowey D, Carroll AE, Daniels SR, de Ferranti SD, Dionne JM, Falkner B, Gidding SS, Goodwin C, Leu MG, Powers ME, Rea C, Samuels J, Simasek M, Thaker VV, Urbina EM; SUBCOMMITTEE ON SCREENING AND MANAGEMENT OF HIGH BP IN CHILDREN. Diagnosis, Evaluation, and Management of High Blood Pressure in Children and Adolescents. Pediatrics. 2018 Sep;142(3):e20182096. doi: 10.1542/peds.2018-2096. Epub 2018 Aug 20.

  PMID: 30126937 BACKGROUND

• Moore KP, Wong F, Gines P, Bernardi M, Ochs A, Salerno F, Angeli P, Porayko M, Moreau R, Garcia-Tsao G, Jimenez W, Planas R, Arroyo V. The management of ascites in cirrhosis: report on the consensus conference of the International Ascites Club. Hepatology. 2003 Jul;38(1):258-66. doi: 10.1053/jhep.2003.50315.

  PMID: 12830009 BACKGROUND

• Singh V, Dhungana SP, Singh B, Vijayverghia R, Nain CK, Sharma N, Bhalla A, Gupta PK. Midodrine in patients with cirrhosis and refractory or recurrent ascites: a randomized pilot study. J Hepatol. 2012 Feb;56(2):348-54. doi: 10.1016/j.jhep.2011.04.027. Epub 2011 Jul 13.

  PMID: 21749847 BACKGROUND

• Tanaka H, Fujita Y, Takenaka Y, Kajiwara S, Masutani S, Ishizaki Y, Matsushima R, Shiokawa H, Shiota M, Ishitani N, Kajiura M, Honda K; Task Force of Clinical Guidelines for Child Orthostatic Dysregulation, Japanese Society of Psychosomatic Pediatrics. Japanese clinical guidelines for juvenile orthostatic dysregulation version 1. Pediatr Int. 2009 Feb;51(1):169-79. doi: 10.1111/j.1442-200X.2008.02783.x.

  PMID: 19371306 BACKGROUND

• Zhang F, Li X, Ochs T, Chen L, Liao Y, Tang C, Jin H, Du J. Midregional pro-adrenomedullin as a predictor for therapeutic response to midodrine hydrochloride in children with postural orthostatic tachycardia syndrome. J Am Coll Cardiol. 2012 Jul 24;60(4):315-20. doi: 10.1016/j.jacc.2012.04.025.

  PMID: 22813609 BACKGROUND

MeSH Terms

Conditions

Ascites

Interventions

Midodrine

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Study Officials

• Bassam Ayoub, MD

  Pediatric Hepatology Dep; National Liver Institute, Menoufia University, Egypt

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bassam Ayoub, MD

CONTACT

+201000936418; bassamayob@yahoo.com

Mohamed Abdel Hafeez, MD

CONTACT

+201002362768; abdelhafeez64@yahoo.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2019
• First Posted: August 2, 2019
• Study Start: June 5, 2020
• Primary Completion: June 5, 2021
• Study Completion: December 1, 2021
• Last Updated: August 24, 2020

Record last verified: 2020-08

Locations

EG (1)