Ignite Creation Date:
2025-12-24 @ 1:21 PM
Ignite Modification Date:
2025-12-29 @ 3:23 AM
Study NCT ID:
NCT03547895
Status:
COMPLETED
Last Update Posted:
2018-12-05
First Post:
2017-05-27
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Management of Decompensated HCV Cirrhotic Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D000069474', 'term': 'Sofosbuvir'}, {'id': 'C549273', 'term': 'daclatasvir'}, {'id': 'D012254', 'term': 'Ribavirin'}, {'id': 'D014812', 'term': 'Vitamin K'}, {'id': 'D010837', 'term': 'Vitamin K 1'}, {'id': 'D005665', 'term': 'Furosemide'}, {'id': 'D013148', 'term': 'Spironolactone'}, {'id': 'C000713827', 'term': 'milk-thistle extract'}, {'id': 'D012838', 'term': 'Silymarin'}], 'ancestors': [{'id': 'D014542', 'term': 'Uridine Monophosphate'}, {'id': 'D014500', 'term': 'Uracil Nucleotides'}, {'id': 'D011742', 'term': 'Pyrimidine Nucleotides'}, {'id': 'D011743', 'term': 'Pyrimidines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D009711', 'term': 'Nucleotides'}, {'id': 'D009706', 'term': 'Nucleic Acids, Nucleotides, and Nucleosides'}, {'id': 'D012265', 'term': 'Ribonucleotides'}, {'id': 'D012263', 'term': 'Ribonucleosides'}, {'id': 'D009705', 'term': 'Nucleosides'}, {'id': 'D009285', 'term': 'Naphthoquinones'}, {'id': 'D009281', 'term': 'Naphthalenes'}, {'id': 'D011084', 'term': 'Polycyclic Aromatic Hydrocarbons'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D010836', 'term': 'Phytol'}, {'id': 'D004224', 'term': 'Diterpenes'}, {'id': 'D013729', 'term': 'Terpenes'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D011809', 'term': 'Quinones'}, {'id': 'D013424', 'term': 'Sulfanilamides'}, {'id': 'D013449', 'term': 'Sulfonamides'}, {'id': 'D000577', 'term': 'Amides'}, {'id': 'D000814', 'term': 'Aniline Compounds'}, {'id': 'D000588', 'term': 'Amines'}, {'id': 'D013450', 'term': 'Sulfones'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D007783', 'term': 'Lactones'}, {'id': 'D011283', 'term': 'Pregnenes'}, {'id': 'D011278', 'term': 'Pregnanes'}, {'id': 'D013256', 'term': 'Steroids'}, {'id': 'D000072473', 'term': 'Fused-Ring Compounds'}, {'id': 'D044947', 'term': 'Flavonolignans'}, {'id': 'D005419', 'term': 'Flavonoids'}, {'id': 'D002867', 'term': 'Chromones'}, {'id': 'D001578', 'term': 'Benzopyrans'}, {'id': 'D011714', 'term': 'Pyrans'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'patients with decompensated cirrhosis with frequent hepatic encephalopathy (HE) or difficult to treat ascites were included if they had chronic active HCV'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 80}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2015-06-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2018-12', 'completionDateStruct': {'date': '2018-06-24', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2018-12-03', 'studyFirstSubmitDate': '2017-05-27', 'studyFirstSubmitQcDate': '2018-06-04', 'lastUpdatePostDateStruct': {'date': '2018-12-05', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2018-06-06', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2016-05-24', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'sustained virological response', 'timeFrame': '3 months after 3 months after treatment termination', 'description': 'undetectable HCV RNA 3 months after treatment termination by Polymerase Chain Reaction'}], 'secondaryOutcomes': [{'measure': 'improved liver synthetic function', 'timeFrame': '24 months', 'description': 'improvement of serum albumin'}, {'measure': 'improved liver synthetic function', 'timeFrame': '24 months', 'description': 'improvement of coagulation profile'}, {'measure': 'improved liver excretory function', 'timeFrame': '24 hours', 'description': 'improvement of serum total bilirubin'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Decompensated Cirrhosis']}, 'referencesModule': {'references': [{'pmid': '30758786', 'type': 'DERIVED', 'citation': 'Hanafy AS, Bassiony MA, Basha MAA. Management of HCV-related decompensated cirrhosis with direct-acting antiviral agents: who should be treated? Hepatol Int. 2019 Mar;13(2):165-172. doi: 10.1007/s12072-019-09933-8. Epub 2019 Feb 13.'}]}, 'descriptionModule': {'briefSummary': '-The limited treatment varieties of decompensated cirrhosis due to hepatitis C virus (HCV) remain a challenge. In patients with reduced hepatic reserve, DAAs may be associated with complications as worsening decompensation. The impact of DAAs therapy on mortality in decompensated cirrhosis was not investigated.', 'detailedDescription': "An observational case-control study which was conducted from June 2015 till the first of January 2018 in the Hepatology clinic - Zagazig University hospital-Egypt which is a tertiary referral center.\n\nOut of 422 patients presented with decompensated cirrhosis due to HCV, 342 patients were excluded due to Hepatocellular carcinoma (n=61), cirrhotic cardiomyopathy (n=21), renal impairment (n=34), ischemic heart disease (n=37), active gastrointestinal bleeding (n=42), avoided treatment with DAAs and preferred conservative therapy (n=147); finally 80 patients with decompensated cirrhosis who were willing to be treated and showed frequent hepatic encephalopathy (HE) or difficult to treat ascites were selected to receive DAAs and included if they had chronic HCV proved by the positivity of HCV RNA and elevated transaminases. Their CTP score was \\>9, MELD score was \\<29 Patients were excluded if they had compensated cirrhosis or HCV without cirrhosis; exposure to previous antiviral therapy; hepatocellular carcinoma; other causes of liver diseases or mixed causes as excessive alcohol consumption, autoimmune liver disease; previous liver transplantation; patients with risk factors of myocardial dysfunction as abnormal T wave in electrocardiogram, ejection fraction (EF) less than 50%, left ventricular ejection fraction (LVEF) less than 50%.\n\nThe control group included 80 patients; they sought medical care at the Hepatology outpatient clinic-Zagazig University hospital. They had decompensated liver disease and preferred to be managed conservatively; they desired to avoid treatment by DAAs by themselves (n=43) or by their relatives (n=37) as they were concerned about the potential risk of liver cancer after direct antiviral agents. They were age, sex, CTP and MELD scores matched with the same inclusion and exclusion criteria and had been chosen from the patients who refused the treatment with DAAs (n=147) after their consent to participate in the study, while the remaining patients refused to be enrolled (n=67).\n\nB-Baseline laboratory investigation\n\n* Investigations preliminary to antiviral therapy as liver function tests, Prothrombin time, Prothrombin concentration (%), kidney function tests, complete Blood Count, fasting blood sugar, HBA1c if diabetes was present and serum AFP. For each patient, CTP and MELD scores were calculated.\n* Quantitative assessment of HCV load in the serum by real-time Quantitative PCR (COBAS Ampliprep/Taqman HCV monitor version 2.0, with a detection limit of 15 IU/ml; Roche Diagnostic Systems, just before the study in both groups and after the first month, at the end of treatment and 3 months post-treatment to detect SVR 12th in DAAs treated group\n* Genotyping for HCV using INNO-LiPA II, based on genotype-specific oligonucleotides from the 5' UTR that are immobilized on a nitrocellulose strip. The probe reactivity patterns were interpreted according to the manufacturer instructions.\n\nC- Abdominal Ultrasonography (USG) The patients were evaluated for criteria of decompensated cirrhosis including shrunken cirrhotic liver and ascites, patients with HCC were excluded. Criteria of portal hypertension as portal vein diameter \\> 13mm or cavernous transformation, splenic bipolar diameter \\>13 cm, splenic vein diameter \\>8 mm or the presence of splenic collaterals. After treatment termination; USG was done every 6 months for a period of 20 months for early detection of HCC or worsening of hepatic decompensation.\n\nD- Treatment exposure and outcome\n\n* Medications The study patients will be given Sofosbuvir 400mg, ribavirin 400mg, and daclatasvir 60 mg for 3 months and will be evaluated for the development of sustained virological response (SVR), the occurrence of complications after DAAs and the effects of SVR on the frequency of hepatic encephalopathy, improvement in ascites control or difficult to treat ascites defined as ascites that rapidly recurs after paracentesis or cannot be completely mobilized despite maximal medications (sodium restriction of less than 2 g/day with maximal dose of furosemide (160 mg) or spironolactone (400 mg) or inability to reach maximum diuretic dose due to emergence of side effects, and after confirming compliance with sodium restrictions if the 24-hour urine sodium level is \\<78 mEq, also the impact of therapy on Survival.\n* Monitoring\n* All the patients will have regular biweekly visits in the first 6 months then every 2 months for 20 months. Every visit a full history taking, laboratory evaluation which included complete blood count (CBC), serum creatinine, total and direct bilirubin, serum albumin, serum transaminases, coagulation profile and AFP.\n\nThe patients who did not complete the follow-up will be excluded from the study."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* chronic active HCV proved by the positivity of HCV RNA, elevated transaminases.\n* CTP score was \\>9, MELD score was \\<29\n* Decompensated cirrhosis with frequent hepatic encephalopathy (HE) or difficult to treat ascites\n\nExclusion Criteria:\n\n* exposure to previous antiviral therapy\n* hepatocellular carcinoma\n* other causes of liver diseases or mixed causes (excessive alcohol consumption, autoimmune liver disease)\n* previous liver transplantation.'}, 'identificationModule': {'nctId': 'NCT03547895', 'briefTitle': 'Management of Decompensated HCV Cirrhotic Patients', 'organization': {'class': 'OTHER_GOV', 'fullName': 'Zagazig University'}, 'officialTitle': 'Real Life Experience in the Management of HCV Related Decompensated Cirrhosis With Direct Antiviral Agents', 'orgStudyIdInfo': {'id': '3778'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'cases', 'description': 'patients with decompensated cirrhosis\n\ntreated with Sofosbuvir 400 mg (Sovaldi) + Daclatasvir 60mg (Daklinza) + Ribavirin 200 mg (Rebetol)', 'interventionNames': ['Drug: Sofosbuvir 400mg (Sovaldi) + Daclatasvir 60 mg (Daklinza) + Ribavirin 200 mg (Rebetol)']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'control group', 'description': 'the control group treated with liver support including silymarin 140 + phytomenadione 10 mg + lasilactone 50 mg + albumin infusion', 'interventionNames': ['Drug: vitamin K (Phytomenadione) 10 mg+ furosemide and spironolactone (Lasilactone) 50 mg + milk thistle (Silymarin) 140 mg + Albumin infusion']}], 'interventions': [{'name': 'Sofosbuvir 400mg (Sovaldi) + Daclatasvir 60 mg (Daklinza) + Ribavirin 200 mg (Rebetol)', 'type': 'DRUG', 'otherNames': ['Direct Acting Antivirals (DAAs)'], 'description': 'sofosbuvir 400mg+ribavirin 400mg+daclatasvir 60 mg were adminstered for 3 months', 'armGroupLabels': ['cases']}, {'name': 'vitamin K (Phytomenadione) 10 mg+ furosemide and spironolactone (Lasilactone) 50 mg + milk thistle (Silymarin) 140 mg + Albumin infusion', 'type': 'DRUG', 'otherNames': ['liver support therapy'], 'description': 'symptomatic therapy for liver support, control of ascites and bleeding tendency.', 'armGroupLabels': ['control group']}]}, 'contactsLocationsModule': {'overallOfficials': [{'name': 'Amr S Hanafy, md', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Assistant prof of medicine-Zagazig University'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Zagazig University', 'class': 'OTHER_GOV'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Assistant professor', 'investigatorFullName': 'Amr Shaaban Hanafy', 'investigatorAffiliation': 'Zagazig University'}}}}