Ignite Creation Date:
2025-12-25 @ 12:14 AM
Ignite Modification Date:
2025-12-25 @ 10:16 PM
Study NCT ID:
NCT04043858
Status:
UNKNOWN
Last Update Posted:
2020-08-24
First Post:
2019-08-01
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Safety and Efficacy of Midodrine Hydrochloride in the Management of Refractory Ascites Due to Cirrhosis in Children
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001201', 'term': 'Ascites'}], 'ancestors': [{'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D008879', 'term': 'Midodrine'}], 'ancestors': [{'id': 'D004983', 'term': 'Ethanolamines'}, {'id': 'D000605', 'term': 'Amino Alcohols'}, {'id': 'D000438', 'term': 'Alcohols'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D000588', 'term': 'Amines'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 20}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2020-06-05', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-08', 'completionDateStruct': {'date': '2021-12-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2020-08-20', 'studyFirstSubmitDate': '2019-08-01', 'studyFirstSubmitQcDate': '2019-08-01', 'lastUpdatePostDateStruct': {'date': '2020-08-24', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2019-08-02', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-06-05', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Side effect no 1', 'timeFrame': '3 months', 'description': 'number of patients with Elevated BP: ≥90th percentile to \\<95th percentile'}, {'measure': 'Side effect no 2', 'timeFrame': '3 months', 'description': '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)'}, {'measure': 'Side effect no 3', 'timeFrame': '3 months', 'description': '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)'}, {'measure': 'Side effect no 4', 'timeFrame': '3 months', 'description': 'number of patients with low heart rate'}, {'measure': 'Side effect no 5', 'timeFrame': '3 months', 'description': 'number of patients with urine retention'}, {'measure': 'Side effect no 6', 'timeFrame': '3 months', 'description': 'number of patients with severe itching'}, {'measure': 'Side effect no 7', 'timeFrame': '3 months', 'description': 'number of patients with skin rash'}], 'secondaryOutcomes': [{'measure': 'Complete Response', 'timeFrame': '12 months', 'description': 'absence of ascites by abdominal ultrasound'}, {'measure': 'Partial response', 'timeFrame': '12 months', 'description': 'ascites cannot be mobilized completely but not symptomatic or needs paracentesis'}, {'measure': 'non-response', 'timeFrame': '3 months', 'description': 'no decrease in ascites which still in need for paracentesis after 3 months of duration'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Refractory Ascites', 'Children, Only']}, 'referencesModule': {'references': [{'pmid': '16139922', 'type': 'BACKGROUND', 'citation': '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': '28895701', 'type': 'BACKGROUND', 'citation': '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': '15920323', 'type': 'BACKGROUND', 'citation': 'Cardenas A, Arroyo V. Refractory ascites. Dig Dis. 2005;23(1):30-8. doi: 10.1159/000084723.'}, {'pmid': '21301135', 'type': 'BACKGROUND', 'citation': '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': '29035421', 'type': 'BACKGROUND', 'citation': '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': '24369273', 'type': 'BACKGROUND', 'citation': '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': '27622998', 'type': 'BACKGROUND', 'citation': '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': '30126937', 'type': 'BACKGROUND', 'citation': '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': '12830009', 'type': 'BACKGROUND', 'citation': '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': '21749847', 'type': 'BACKGROUND', 'citation': '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': '19371306', 'type': 'BACKGROUND', 'citation': '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': '22813609', 'type': 'BACKGROUND', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': 'Ascites in liver cirrhosis is explained by increased production of vasoactive substances, such as nitric oxide, carbon monoxide, and endocannabinoids, which cause splanchnic vasodilatation, increased blood flow through this area, and a decrease in peripheral vascular resistance and the effective arterial volume with resulting reduction in renal blood flow with subsequent activation of rennin-angiotensin-aldosterone system which in turn leads 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.\n\nThe International Ascites Club defines refractory ascites as ascites that cannot be mobilized or prevented from early recurrence after large-volume paracentesis despite medical therapy and dietary sodium restriction.\n\nThere are two varieties of refractory ascites: diuretic-resistant ascites that is unresponsive to the maximal tolerable dose of diuretic therapy and diuretic-intractable ascites when complications such as hepatic encephalopathy, renal dysfunction, or electrolyte abnormalities limit the use of diuretics in the effective therapeutic dose (Cárdenas and Arroyo, 2005)\n\nThe therapeutic options for refractory ascites are serial therapeutic paracentesis, transjugular intrahepatic portosystemic shunt, peritoneovenous shunt, and liver transplantation.\n\nMidodrine is transformed into the active metabolite desglymidodrine, which is an α1 receptor agonist causing an increase in vascular tone and increase in blood pressure without β-adrenergic receptors stimulation so, it can improve systemic and renal hemodynamics in non-azotemic cirrhotic patients by counteracting mesenteric vasodilatation, which is accentuated in cirrhosis. It diffuses poorly across the blood-brain barrier with no central effects.\n\nIn a study included 600 adult patients with refractory ascites, midodrine was added to diuretic therapy and lead to enhancement of diuresis with the improvement of systemic, renal hemodynamics and short-term survival. Approximately, the only use of midodrine hydrochloride in children was in postural orthostatic tachycardia syndrome (POTS) which showed a good efficacy and safety profile.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '18 Years', 'minimumAge': '7 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Children aged 7-18 years\n* Both sexes\n* Having refractory ascites (not responding to maximal dose of diuretics\n* Diuretic-induced complications necessitate discontinuation of the drug\n\nExclusion Criteria:\n\n* Non-cirrhotic causes of ascites\n* Intrinsic renal disease ( e.g; polycystic kidney disease)\n* Active gastrointestinal bleeding or the presence of risky varices\n* Patients with Portal vein thrombosis and Budd-Chiari\n* Cardiovascular disease\n* Systemic hypertension or prehypertension\n* Hyperthyroidism\n* Patients with narrow-angle glucoma'}, 'identificationModule': {'nctId': 'NCT04043858', 'briefTitle': 'Safety and Efficacy of Midodrine Hydrochloride in the Management of Refractory Ascites Due to Cirrhosis in Children', 'organization': {'class': 'OTHER', 'fullName': 'National Liver Institute, Egypt'}, 'officialTitle': 'Safety and Efficacy of Midodrine Hydrochloride in the Management of Refractory Ascites Due to Cirrhosis in Children: a Pilot Study', 'orgStudyIdInfo': {'id': 'Mid-Asci-Ped'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Midodrine daily', 'description': 'Midodrine hydrochloride 2.5 mg tab once per day', 'interventionNames': ['Drug: Midodrine 2.5 mg tab']}], 'interventions': [{'name': 'Midodrine 2.5 mg tab', 'type': 'DRUG', 'otherNames': ['ProAmatine'], 'description': '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', 'armGroupLabels': ['Midodrine daily']}]}, 'contactsLocationsModule': {'locations': [{'zip': '32511', 'city': 'Shibīn al Kawm', 'state': 'Menofiya', 'status': 'RECRUITING', 'country': 'Egypt', 'contacts': [{'name': 'Bassam Ayoub, MD', 'role': 'CONTACT', 'email': 'bassamayob@yahoo.com', 'phone': '+201000936418'}, {'name': 'Mohamed Abdel Hafeez, MD', 'role': 'CONTACT', 'email': 'abdelhafeez64@yahoo.com', 'phone': '+201002362768'}, {'name': 'Tahany A Salem, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Marwa S Rizk, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Salma A Nage, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Rasha A Ali, MD', 'role': 'SUB_INVESTIGATOR'}], 'facility': 'Pediatric Hepatology, Gastroenterology and Nutrition Department, National Liver Institute, Menoufia University', 'geoPoint': {'lat': 30.55258, 'lon': 31.00904}}], 'centralContacts': [{'name': 'Bassam Ayoub, MD', 'role': 'CONTACT', 'email': 'bassamayob@yahoo.com', 'phone': '+201000936418'}, {'name': 'Mohamed Abdel Hafeez, MD', 'role': 'CONTACT', 'email': 'abdelhafeez64@yahoo.com', 'phone': '+201002362768'}], 'overallOfficials': [{'name': 'Bassam Ayoub, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Pediatric Hepatology Dep; National Liver Institute, Menoufia University, Egypt'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'National Liver Institute, Egypt', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}