Ignite Creation Date:
2025-12-24 @ 10:54 PM
Ignite Modification Date:
2026-01-01 @ 4:57 AM
Study NCT ID:
NCT04485169
Status:
COMPLETED
Last Update Posted:
2020-09-28
First Post:
2020-07-21
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Therapeutic Plasma Exchange for Coronavirus Disease-2019 Triggered Cytokine Release Storm;
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000086382', 'term': 'COVID-19'}, {'id': 'D000080424', 'term': 'Cytokine Release Syndrome'}], 'ancestors': [{'id': 'D011024', 'term': 'Pneumonia, Viral'}, {'id': 'D011014', 'term': 'Pneumonia'}, {'id': 'D012141', 'term': 'Respiratory Tract Infections'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D014777', 'term': 'Virus Diseases'}, {'id': 'D018352', 'term': 'Coronavirus Infections'}, {'id': 'D003333', 'term': 'Coronaviridae Infections'}, {'id': 'D030341', 'term': 'Nidovirales Infections'}, {'id': 'D012327', 'term': 'RNA Virus Infections'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D018746', 'term': 'Systemic Inflammatory Response Syndrome'}, {'id': 'D007249', 'term': 'Inflammation'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D012769', 'term': 'Shock'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D010951', 'term': 'Plasma Exchange'}], 'ancestors': [{'id': 'D001803', 'term': 'Blood Transfusion'}, {'id': 'D001691', 'term': 'Biological Therapy'}, {'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D010956', 'term': 'Plasmapheresis'}, {'id': 'D001781', 'term': 'Blood Component Removal'}, {'id': 'D016060', 'term': 'Sorption Detoxification'}, {'id': 'D005112', 'term': 'Extracorporeal Circulation'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'It was an interventional retrospective Propensity score matched (PSM) single centre based cohort study in Pak Emirates Military Hospital Rawalpindi (PEMH), Pakistan from 1st April to 30th June 2020. This study was carried out at the Department of Pulmonology and Critical care. PEMH is the largest Covid-19 designated hospital in the country. Data of all hospitalized patients is maintained by PEMH Covid-19 Research and evaluation cell. The study was approved by Institutional Review Board.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 280}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2020-04-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-09', 'completionDateStruct': {'date': '2020-07-31', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-09-24', 'studyFirstSubmitDate': '2020-07-21', 'studyFirstSubmitQcDate': '2020-07-22', 'lastUpdatePostDateStruct': {'date': '2020-09-28', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-07-24', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2020-07-31', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Survival', 'timeFrame': '28 days', 'description': 'Death or recovery'}], 'secondaryOutcomes': [{'measure': 'Duration of Hospitalization', 'timeFrame': '28 days', 'description': 'Duration of hospitalization in days'}, {'measure': 'Timing of PCR negativity', 'timeFrame': '28 days', 'description': 'Time in days to achieve viral clearance'}, {'measure': 'Time to CRS resolution', 'timeFrame': '28 days', 'description': 'Time in days required to settle symptoms and laboratory parameters of CRS'}, {'measure': 'Complications', 'timeFrame': '28 days', 'description': 'Complications secondary to use of TPE'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Therapeutic Plasma exchange', 'Cytokine release storm', 'COVID-19', 'ARDS', 'Critical disease'], 'conditions': ['COVID-19', 'Cytokine Release Syndrome']}, 'referencesModule': {'references': [{'type': 'BACKGROUND', 'citation': '6. Clinical Management Guidelines for COVID-19 Infections, Version 2 [Internet]. Nhsrc.gov.pk. 2020 [cited 1 July 2020]. Available from: http://www.nhsrc.gov.pk/SiteImage/Misc/files/Clinical-Management-nfection%20v2.pdf'}, {'pmid': '31180581', 'type': 'BACKGROUND', 'citation': 'Padmanabhan A, Connelly-Smith L, Aqui N, Balogun RA, Klingel R, Meyer E, Pham HP, Schneiderman J, Witt V, Wu Y, Zantek ND, Dunbar NM, Schwartz GEJ. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice - Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue. J Clin Apher. 2019 Jun;34(3):171-354. doi: 10.1002/jca.21705.'}, {'pmid': '20453703', 'type': 'BACKGROUND', 'citation': 'Patel P, Nandwani V, Vanchiere J, Conrad SA, Scott LK. Use of therapeutic plasma exchange as a rescue therapy in 2009 pH1N1 influenza A--an associated respiratory failure and hemodynamic shock. Pediatr Crit Care Med. 2011 Mar;12(2):e87-9. doi: 10.1097/PCC.0b013e3181e2a569.'}, {'pmid': '12373468', 'type': 'BACKGROUND', 'citation': 'Busund R, Koukline V, Utrobin U, Nedashkovsky E. Plasmapheresis in severe sepsis and septic shock: a prospective, randomised, controlled trial. Intensive Care Med. 2002 Oct;28(10):1434-9. doi: 10.1007/s00134-002-1410-7. Epub 2002 Jul 23.'}, {'pmid': '32241301', 'type': 'BACKGROUND', 'citation': 'Keith P, Day M, Perkins L, Moyer L, Hewitt K, Wells A. A novel treatment approach to the novel coronavirus: an argument for the use of therapeutic plasma exchange for fulminant COVID-19. Crit Care. 2020 Apr 2;24(1):128. doi: 10.1186/s13054-020-2836-4. No abstract available.'}, {'pmid': '32298745', 'type': 'BACKGROUND', 'citation': 'Shi H, Zhou C, He P, Huang S, Duan Y, Wang X, Lin K, Zhou C, Zhang X, Zha Y. Successful treatment with plasma exchange followed by intravenous immunoglobulin in a critically ill patient with COVID-19. Int J Antimicrob Agents. 2020 Aug;56(2):105974. doi: 10.1016/j.ijantimicag.2020.105974. Epub 2020 Apr 13.'}, {'pmid': '32453903', 'type': 'BACKGROUND', 'citation': 'Zhang L, Zhai H, Ma S, Chen J, Gao Y. Efficacy of therapeutic plasma exchange in severe COVID-19 patients. Br J Haematol. 2020 Aug;190(4):e181-e183. doi: 10.1111/bjh.16890. Epub 2020 Jun 12. No abstract available.'}, {'pmid': '32247038', 'type': 'BACKGROUND', 'citation': 'Ma J, Xia P, Zhou Y, Liu Z, Zhou X, Wang J, Li T, Yan X, Chen L, Zhang S, Qin Y, Li X. Potential effect of blood purification therapy in reducing cytokine storm as a late complication of critically ill COVID-19. Clin Immunol. 2020 May;214:108408. doi: 10.1016/j.clim.2020.108408. Epub 2020 Apr 1. No abstract available.'}, {'pmid': '30373638', 'type': 'RESULT', 'citation': 'Knaup H, Stahl K, Schmidt BMW, Idowu TO, Busch M, Wiesner O, Welte T, Haller H, Kielstein JT, Hoeper MM, David S. Early therapeutic plasma exchange in septic shock: a prospective open-label nonrandomized pilot study focusing on safety, hemodynamics, vascular barrier function, and biologic markers. Crit Care. 2018 Oct 30;22(1):285. doi: 10.1186/s13054-018-2220-9.'}]}, 'descriptionModule': {'briefSummary': 'Background:\n\ninvestigators have seen recently from experience in Western countries with best health care systems that pandemics cannot be managed in hospitals. Investigators have seen ICUs crowded to capacity, healthcare workers being exposed and going to quarantine or dying after exposure to large doses of viral inoculums. Investigators recommend that institutions should register for Clinical trials and consider emergency use of TPE. In Pandemics, time is of essence to avoid mortality by intervening early with available evidence, preferably as part of clinical trial.\n\nScientific rationale:\n\nBeyond supportive care, there are currently no proven treatment options for coronavirus disease (COVID-19) and related pneumonia, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). However, literature review has shown that most common cause of death in severe SARS-COV-2 is Cytokine release syndrome and Hemophygocytic Lymphohistocytosis (HLH). In this context, Investigators seek to treat patients who are sick enough to warrant hospitalization prior to the onset of overwhelming disease including a systemic inflammatory response, sepsis, and/or Acute Respiratory Distress Syndrome (ARDS).', 'detailedDescription': 'PROTOCOL SUMMARY:\n\nTherapeutic plasma exchange for coronavirus disease-2019 triggered cytokine release storm; a retrospective propensity matched control study\n\nClinical Phase: Two arms, Phase 2 Open Label\n\nConducted by: Department of Pulmonology and Critical Care; Pak Emirates Military Hospital.\n\nSample Size: 280\n\nStudy Population: Hospitalized COVID-19 patients aged ≥18 years to 80 years of with Moderate- severe-critical disease and evidence of Cytokine release storm (CRS)\n\nStudy Duration: 1st April, 2020 to 31st July 2020\n\nStudy Design: A retrospective propensity matched control trial will assess the efficacy and safety of following treatment options\n\n1. Standard treatment including steroids\n2. Therapeutic plasma exchange in addition to standard treatment\n\nOperational Definitions\n\n1. Moderate disease:\n\n COVID-19 positive case with lung infiltrates \\< 50% of total lung fields on Chest X-ray / peripheral ground glass opacities (GGOs) on High Resolution Computerized Tomography (HRCT)chest but no evidence of hypoxemia.\n2. Severe disease:\n\n COVID-19 pneumonia with evidence of hypoxemia (RR \\> 30/minute or PaO2 on ABGs \\< 80mmHg or PaO2/FiO2 (PF ratio) \\< 300 or lung infiltrates \\> 50% of the lung field).\n3. Critical illness:\n\n COVID-19 pneumonia with evidence of either respiratory failure (PaO2 \\< 60mmHg) or multiorgan dysfunction syndrome (MODS) measured by Sequential Organ Failure assessment (SOFA score) \\> 10 or septic shock (Systolic BP less than 90 or less than 40mm Hg of baseline in hypertensive or Urine output \\< 0.5 ml/kg/hour).Age, sex, comorbidities, date of symptoms, source of infection, type of admission SOFA score, Clinical status, vital signs including temperature, respiratory rate, oxygen saturation, oxygen requirement, Complete Blood counts (CBC) with neutrophil counts, lymphocytes count, C-reactive Proteins (CRP), chest imaging (CT or X-ray), location and status in hospital\n4. Cytokine release storm (CRS):\n\nDiagnostic criteria of Cytokine release syndrome (CRS) CRS is defined as fever of equal to or more than 100 F persisting \\> 48 hours in absence of documented bacterial infection and ANY of the following in the presence of moderate, severe or critical disease\n\n1. Ferritin \\>1000 mcg/L and rising in last 24 hours\n2. Ferritin \\>2000 mcg/L in patient requiring high flow oxygen or ventilation\n3. Lymphopenia \\< 800 cells/ul or lymphocyte percentage \\<20% and two of the following\n\n 1. Ferritin \\>700 mcg/mL and rising in the last 24 hours\n 2. LDH \\> 300 IU (reference 140-250 IU/L) and rising in the last 24 hours\n 3. D-Dimer \\>1000ng/mL (or \\>1mcg/ml) and rising in the last 24 hours\n 4. CRP \\>70 mg/L (or \\>10 hsCRP) and rising in the last 24 hours, in absence of bacterial infection\n 5. If any 3 of above presents on admission no need to document rise\n\n5\\. Standard treatment:\n\nAs per Institutional COVID-19 Management Guidelines all patients of moderate, severe and critical COVID-19 received standard protocol of aspirin, anticoagulation, ulcer prophylaxis, awake Proning (if PaO2 \\< 80mmHg) and corticosteroids. All patients of CRS received Methylprednisolone 1 mg/kg irrespective of disease severity.\n\n6\\. Therapeutic Plasma exchange (TPE)\n\nTherapeutic plasma exchange: 1-1.5 plasma exchange daily (1-5 sessions) with replacement fluid Fresh frozen Plasma (FFP) (whole volume) to 70 willing patients of moderate, severe and critical disease with evidence of CRS after explaining the investigational role of this therapy. TPE will be given in addition to standard treatment to 70 patients randomly. TPE related complications to be documented\n\n7\\. Recovery Recovery to be defined by de-escalation of patients condition from severe to moderate, or from moderate to mild, plus at least 2 of the following; serum Ferritin \\< 1000 ug/ml (and decreasing trend on two consecutive days), serum LDH normalization, C-reactive protein \\> 50% fold reduction (and decreasing trend in on two consecutive days),), ALC \\> 1000 and PT/APTT normalization.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* COVID-19 diagnosed by Polymerase Chain Reaction (PCR) positivity for SARS-CoV2\n* CRS at presentation or developing during hospitalization\n* 10-80 years age and both genders\n* hospital admission\n* At least 1 completed session of plasma-exchange in patients included in TPE arm\n* No other novel therapy administered.\n\nExclusion criteria were:\n\n* Death within 48 hours of admission\n* severe septic shock at time of admission\n* Congestive cardiac failure (EF\\<20%) (4)\n* Those receiving immunotherapy, Anti-thymocyte globulin or hematopoietic stem cell transplant in recent past\n* Patients of hematological or solid organ malignancies\n* patients receiving other investigational drugs including Tocilizumab, Convalescent plasma, Remdesivir, or Mesenchymal stem cells.'}, 'identificationModule': {'nctId': 'NCT04485169', 'acronym': 'Plex', 'briefTitle': 'Therapeutic Plasma Exchange for Coronavirus Disease-2019 Triggered Cytokine Release Storm;', 'organization': {'class': 'OTHER', 'fullName': 'UNICEF'}, 'officialTitle': 'Therapeutic Plasma Exchange for Coronavirus Disease-2019 Triggered Cytokine Release Storm; a Retrospective Propensity Matched Control Study', 'orgStudyIdInfo': {'id': 'Sultan Mehmood Kamran'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'TPE Arm', 'description': "In addition to standard care TPE was performed once daily using COBE Spectra Apheresis machine version 7 (Manufacturer TERUMO BCT, Lakewood, CO, USA INC) having continuous flow centrifugation. Venous access was achieved using an ultrasound guided double lumen catheter (Arrow - 12 FR) via femoral vein. Patient's total blood volume was calculated as per Nadler's formula. Anticoagulant acid dextrose ratio was 1:10 and flow rate 30-40 ml/minutes (Adjusted as per hemodynamic status). Patients' blood pressure, pulse, oxygen saturation was monitored throughout procedure. Duration of procedure varied from 2-4 hours and 1-1.5 times total plasma volume was removed during each procedure. Replacement fluid was fresh frozen plasma (FFP) and normal saline in 2:1 respectively. All procedures were performed in intensive care or high dependency unit by Apheresis Department of PEMH. TPE was continued till recovery", 'interventionNames': ['Procedure: Therapeutic Plasma Exchange']}, {'type': 'NO_INTERVENTION', 'label': 'NON TPE arm', 'description': 'Only supportive treatment offered including Vit C, Zinc, Vit D, famotidine, Enoxaparin and Methylprednisolone'}], 'interventions': [{'name': 'Therapeutic Plasma Exchange', 'type': 'PROCEDURE', 'description': 'a. 1-1.5 plasma volume exchange, 2/3rd plasma should be replacing with FFP to avoid coagulopathy, adequate dieresis to prevent volume overload, 1-5 sessions in total, 1 session daily', 'armGroupLabels': ['TPE Arm']}]}, 'contactsLocationsModule': {'locations': [{'zip': '46000', 'city': 'Rawalpindi', 'state': 'Punjab Province', 'country': 'Pakistan', 'facility': 'Pak Emirates Military Hospital', 'geoPoint': {'lat': 33.59733, 'lon': 73.0479}}], 'overallOfficials': [{'name': 'Imran m Fazal, FCPS', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Pak Emirates Military Hospital (PEMH) Rawalpindi'}]}, 'ipdSharingStatementModule': {'infoTypes': ['STUDY_PROTOCOL', 'SAP', 'ICF'], 'timeFrame': 'Data is available right now and will remain available (6 months)', 'ipdSharing': 'YES', 'description': 'data can be shared on demand in SPSS sheet', 'accessCriteria': 'By email'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'UNICEF', 'class': 'OTHER'}, 'collaborators': [{'name': 'Pak Emirates Military Hospital Rawalpindi', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Classified Medical specialist', 'investigatorFullName': 'sultan mehmood kamran', 'investigatorAffiliation': 'UNICEF'}}}}