NCT04521309

Brief Summary

Severe and critically ill patients will be enrolled in the study (50 patients) after duly filled consent forms. Recipients shall be divided in to 5 groups with 10 patients per group to compare clinical efficacy and safety of patients in clinical phase I/phase II study. Each group shall receive particular single dose of Intravenously administered Immunoglobulins (IVIG) developed from convalescent plasma of recovered COVID-19 individual , an experimental drug along with standard treatment except for control group which will receive standard treatment only.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P50-P75 for phase_1 covid19

Timeline
Completed

Started Jun 2020

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 7, 2020

Completed
1 month until next milestone

Study Start

First participant enrolled

June 19, 2020

Completed
2 months until next milestone

First Posted

Study publicly available on registry

August 20, 2020

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 26, 2021

Completed
13 days until next milestone

Study Completion

Last participant's last visit for all outcomes

February 8, 2021

Completed
Last Updated

March 24, 2021

Status Verified

March 1, 2021

Enrollment Period

7 months

First QC Date

May 7, 2020

Last Update Submit

March 21, 2021

Conditions

COVID-19

Keywords

COVID19 ( Corona Virus Disease -2019)SARS-CoV-2 (Severe Acute respiratory syndrome Coronavirus 2)Passive ImmunizationIntravenous Immunoglobulin (IVIG)Pooled convalescent PlasmaCritically ill COVID-19 patientsSevere COVID-19 patientsAntibody

Outcome Measures

Primary Outcomes (8)

  • 28 Days mortality

    All cause mortality of participants will be monitored for 28 days to assess the safety and efficacy of IVIG treatment.

    28 days

  • Requirement of supplemental oxygen support

    Number of days required for invasive or non-invasive oxygen supply during hospital stay as per oxygen saturation status of patient

    28 days

  • Number of days on assisted ventilation

    Number of days a participant will be requiring assisted ventilation both invasive and noninvasive

    28 days

  • Days to step down

    Shifting from ICU to ward

    28 days

  • Days to Hospital Discharge

    Duration from day of enrollment in study to Day of hospital discharge

    28 days

  • Adverse events during hospital stay

    Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI)

    28 days

  • Change in C-Reactive Protein (CRP) levels

    Change in C-Reactive Protein (CRP) levels from baseline will be used to monitor inflammation

    28 days

  • Change in neutrophil lymphocyte ratio

    change in neutrophil lymphocyte ratio from baseline will be used to monitor inflammation

    28 days

Secondary Outcomes (10)

  • Change in Ferritin levels

    28 days

  • Change in lactate dehydrogenase (LDH) levels

    28 days

  • Change in radiological (X-ray) findings

    28 days

  • Days to negative SARS-CoV-2 Polymerase Chain Reaction (PCR) test

    28 days

  • Anti-SARS-CoV-2 Antibody

    28 days

  • +5 more secondary outcomes

Study Arms (5)

Control

NO INTERVENTION

Standard care only n = 10 patients.

IVIG dose: 0.15 g/kg

EXPERIMENTAL

Standard Care + Single dose of 0.20 g/Kg anti-COVID-19 IVIG (experimental drug prepared at DUHS) n= 10 patients

Biological: SARS-CoV-2 antibody based IVIG therapy

IVIG dose: 0.20 g/kg

EXPERIMENTAL

Standard Care + Single dose of 0.25 g/Kg anti-COVID19 IVIG (experimental drug prepared at DUHS) n= 10 patients

Biological: SARS-CoV-2 antibody based IVIG therapy

IVIG dose: 0.25 g/kg

EXPERIMENTAL

Standard Care + Single dose of 0.30 g/Kg anti-COVID19 IVIG (experimental drug prepared at DUHS) n= 10 patients

Biological: SARS-CoV-2 antibody based IVIG therapy

IVIG dose: 0.30 g/kg

EXPERIMENTAL

Standard Care + Single dose of 0.35 g/Kg anti-COVID19 IVIG (experimental drug prepared at DUHS) n= 10 patients

Biological: SARS-CoV-2 antibody based IVIG therapy

Interventions

SARS-CoV-2 antibody based IVIG therapyBIOLOGICAL

Patient groups will receive IVIG prepared from pooled convalescent plasma from recovered COVID-19 patients. This will be administered sequentially and in varying dosages, infused over a period of 12 hours, intravenously.Additionally, all treatment groups will receive same standard care as control group. Standard Care as per hospital protocol, which may include: Airway support, Anti-Viral medication, Antibiotics, Fluid Resuscitation, Hemodynamic Support, Steroids, Painkillers, Anti-Pyretics

IVIG dose: 0.15 g/kgIVIG dose: 0.20 g/kgIVIG dose: 0.25 g/kgIVIG dose: 0.30 g/kg

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Above 18 years of age
  • Have positive SARS-CoV-2 PCR on nasopharyngeal and/or oropharyngeal swabs
  • Admitted in isolation ward and ICU of institutes affiliated with DUHS
  • have severe or critical COVID 19 as judged by the treating physician
  • Consent given by the patient or first degree relative

You may not qualify if:

  • Pregnancy
  • Previous allergic reaction to immunoglobulin treatment
  • Ig A deficiency
  • Patient requiring 2 inotropic agents to maintain blood pressures
  • Known case of any autoimmune disorder
  • Acute kidney injury or chronic renal failure
  • Known case of thromboembolic disorder
  • Aseptic meningitis

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Dow University of Health Sciences

Karachi, Sindh, 74200, Pakistan

Location

Related Publications (13)

  • Cunningham AC, Goh HP, Koh D. Treatment of COVID-19: old tricks for new challenges. Crit Care. 2020 Mar 16;24(1):91. doi: 10.1186/s13054-020-2818-6. No abstract available.

    PMID: 32178711BACKGROUND

  • Chen L, Xiong J, Bao L, Shi Y. Convalescent plasma as a potential therapy for COVID-19. Lancet Infect Dis. 2020 Apr;20(4):398-400. doi: 10.1016/S1473-3099(20)30141-9. Epub 2020 Feb 27. No abstract available.

    PMID: 32113510BACKGROUND

  • Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, Wang F, Li D, Yang M, Xing L, Wei J, Xiao H, Yang Y, Qu J, Qing L, Chen L, Xu Z, Peng L, Li Y, Zheng H, Chen F, Huang K, Jiang Y, Liu D, Zhang Z, Liu Y, Liu L. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. 2020 Apr 28;323(16):1582-1589. doi: 10.1001/jama.2020.4783.

    PMID: 32219428BACKGROUND

  • Buchacher A, Iberer G. Purification of intravenous immunoglobulin G from human plasma--aspects of yield and virus safety. Biotechnol J. 2006 Feb;1(2):148-63. doi: 10.1002/biot.200500037.

    PMID: 16892245BACKGROUND

  • Hughes RA, Donofrio P, Bril V, Dalakas MC, Deng C, Hanna K, Hartung HP, Latov N, Merkies IS, van Doorn PA; ICE Study Group. Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial. Lancet Neurol. 2008 Feb;7(2):136-44. doi: 10.1016/S1474-4422(07)70329-0.

    PMID: 18178525BACKGROUND

  • Hung IFN, To KKW, Lee CK, Lee KL, Yan WW, Chan K, Chan WM, Ngai CW, Law KI, Chow FL, Liu R, Lai KY, Lau CCY, Liu SH, Chan KH, Lin CK, Yuen KY. Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection. Chest. 2013 Aug;144(2):464-473. doi: 10.1378/chest.12-2907.

    PMID: 23450336BACKGROUND

  • Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw FM, Lim WS, Makki S, Rooney KD, Nguyen-Van-Tam JS, Beck CR; Convalescent Plasma Study Group. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J Infect Dis. 2015 Jan 1;211(1):80-90. doi: 10.1093/infdis/jiu396. Epub 2014 Jul 16.

    PMID: 25030060BACKGROUND

  • Arabi Y, Balkhy H, Hajeer AH, Bouchama A, Hayden FG, Al-Omari A, Al-Hameed FM, Taha Y, Shindo N, Whitehead J, Merson L, AlJohani S, Al-Khairy K, Carson G, Luke TC, Hensley L, Al-Dawood A, Al-Qahtani S, Modjarrad K, Sadat M, Rohde G, Leport C, Fowler R. Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol. Springerplus. 2015 Nov 19;4:709. doi: 10.1186/s40064-015-1490-9. eCollection 2015.

    PMID: 26618098BACKGROUND

  • Cheng Y, Wong R, Soo YO, Wong WS, Lee CK, Ng MH, Chan P, Wong KC, Leung CB, Cheng G. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis. 2005 Jan;24(1):44-6. doi: 10.1007/s10096-004-1271-9.

    PMID: 15616839BACKGROUND

  • Pandey S, Vyas GN. Adverse effects of plasma transfusion. Transfusion. 2012 May;52 Suppl 1(Suppl 1):65S-79S. doi: 10.1111/j.1537-2995.2012.03663.x.

    PMID: 22578374BACKGROUND

  • Ali S, Uddin SM, Shalim E, Sayeed MA, Anjum F, Saleem F, Muhaymin SM, Ali A, Ali MR, Ahmed I, Mushtaq T, Khan S, Shahab F, Luxmi S, Kumar S, Arain H, Khan M, Khan AS, Mehmood H, Rasheed A, Jahangeer A, Baig S, Quraishy S. Hyperimmune anti-COVID-19 IVIG (C-IVIG) treatment in severe and critical COVID-19 patients: A phase I/II randomized control trial. EClinicalMedicine. 2021 Jun;36:100926. doi: 10.1016/j.eclinm.2021.100926. Epub 2021 Jun 4.

    PMID: 34109306DERIVED

  • Ali S, Uddin SM, Ali A, Anjum F, Ali R, Shalim E, Khan M, Ahmed I, M Muhaymin S, Bukhari U, Luxmi S, Khan AS, Quraishy S. Production of hyperimmune anti-SARS-CoV-2 intravenous immunoglobulin from pooled COVID-19 convalescent plasma. Immunotherapy. 2021 Apr;13(5):397-407. doi: 10.2217/imt-2020-0263. Epub 2021 Feb 9.

    PMID: 33557591DERIVED

  • Ali S, Luxmi S, Anjum F, Muhaymin SM, Uddin SM, Ali A, Ali MR, Tauheed S, Khan M, Bajwa M, Baig SU, Shalim E, Ahmed I, Khan AS, Quraishy S. Hyperimmune anti-COVID-19 IVIG (C-IVIG) Therapy for Passive Immunization of Severe and Critically Ill COVID-19 Patients: A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Nov 2;21(1):905. doi: 10.1186/s13063-020-04839-5.

    PMID: 33138867DERIVED

Related Links

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract Diseases

Study Officials

  • Dr.Shaukat Ali, PhD

    Dow University of Health Sciences, Principal Dow College of Biotechnology

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 7, 2020

First Posted

August 20, 2020

Study Start

June 19, 2020

Primary Completion

January 26, 2021

Study Completion

February 8, 2021

Last Updated

March 24, 2021

Record last verified: 2021-03

Data Sharing

IPD Sharing
Will not share

Locations

PA(1)