Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04549376 |
| Other study ID # |
BRiCM-1131-2020 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
July 1, 2020 |
| Est. completion date |
October 30, 2020 |
Study information
| Verified date |
January 2022 |
| Source |
Bangladesh Reference Institute of Chemical Measurements (BRICM) |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
It is an established fact that, corona virus spread through the respiratory droplets.
Colonization of the virus in oropharynx and/or nasopharynx is considered to be major factor
for transmissibility of the virus through respiratory secretions. Preventing colonization of
the virus by administrating povidone iodine in the nasal passage therefore, a rational
thought which is supported by recent evidence of in-vitro virucidal action of povidone iodine
in Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS CoV-2). Therefore, the study is
designed to assess the virucidal effect of povidone iodine on COVID-19 virus in-vivo.This
open label randomized clinical trial will be conducted at Department of Otorhinolaryngology
and Head Neck Surgery, in collaboration with Department of Virology and Department of
Medicine in Dhaka Medical College (DMC) Hospital. The study will be conducted from September
2020 to October 2020. Total 175 confirmed cases of COVID-19 disease, proven by Reverse
transcription polymerase chain reaction (RT-PCR) testing will be enrolled in this study.
Written informed consent will be ensured before participation. In case of no literacy, finger
print will be considered for written permission.Consent will be sought from the legal
guardian in case of minor or underaged.Formal ethical clearance will be taken from Ethical
Review Committee (ERC) of Dhaka Medical College. All of the Participants will be divided into
seven groups: Group A will receive Povidone iodine (PVP-I) nasal irrigation at concentration
of 0.4%, Group B and Group C will received 0.5% and 0.6%; Group D will receive PVP-I nasal
spray at concentration of 0.5% and Group E will received at 0.6% concentration. Group F
(Placebo comparator group) will receive nasal irrigation by distilled water (DW) and Group G
(Placebo comparator group) will received nasal spray by distilled water. The contact time
will be minimum 30 seconds. After the individual application of PVP-I and distilled water in
respective participant, they will be tested again for RT-PCR for COVID-19 from nasopharyngeal
and oropharyngeal sample. All patients will be subjected to detail history, physical
examination and adverse events. Block Randomization will be followed for randomization. Data
will be recorded in a semi-structured questionnaire and will be analyzed by 'R-4.0.2' data
analysis software
Description:
Rationale of the study
The coronavirus disease 2019 (COVID-19) is a highly infectious disease and cause human to
human transmission primarily by respiratory droplets from coughing, sneezing and speaking. In
early SARS-CoV-2 infection, a greater viral titre can be found in saliva and nasal mucous;
minimization of these titres should help to reduce cross infection. Povidone-iodine (PVP-I)
disinfectant has better anti-viral activity than other antiseptics and has already been
proven to be an extremely effective virucide in vitro against severe acute respiratory
syndrome and Middle East respiratory syndrome coronaviruses (SARS-CoV and MERS-CoV). Its' in
vivo virucidal activity is unknown, though its nasal or oral preparation can be effective in
reducing transmission. Earlier, a very few studies have evaluated the efficacy of
povidone-iodine as nasal antiseptics or oral rinse antiseptics against the SARS-CoV-2 virus
but the result of those studies are not undebatable. So aim of this study is to investigate
the virucidal activity of povidone iodine on coronavirus located on the mucosal surface of
oropharynx and nasopharynx and is very rational in this pandemic period.
Research Hypothesis:
Objectives:
General Objective:
To determine the virucidal efficacy of povidone iodine on COVID-19 virus located in
nasopharynx.
Secondary objectives:
i. To determine the efficacy of povidone iodine to clear COVID-19 virus located in
nasopharynx ii. To assess the adverse events among the groups
Study Design: Open label randomized clinical trial. Place of Study: Department of
Otorhinolaryngology and Head Neck Surgery, in collaboration with Department of Virology and
Department of Medicine, Dhaka Medical College Hospital, Dhaka, Bangladesh.
Period of study: The study period will be September 2020 to November 2020. Study population:
Confirmed cases of COVID-19 disease proven by RT-PCR testing. Sampling and Statistical basis
of the sample size: The sample size is determined using the following formula Sample size:
estimated sample size 189 (twenty seven in each group) Research instruments General
questionnaire for recording baseline information A checklist for for detecting COVID-19
status
Method and data collection:
Participant selection and enrollment: All patients admitted to the medical wards through
emergency department or Outpatient department with suspected COVID-19 cases will be initially
approached and screened for confirmation of the COVID-19. Confirmation of the COVID-19 will
be done by positive impression of RT-PCR result. Following confirmation of the viral
infection, the patients will be seen by the ward doctors and clinical trial physicians
(registered physicians). Moreover, baseline complete blood count (CBC) will be done for each
patient. Chest X-ray/High resolution computed tomography (HRCT) will be done in necessary
case. The ward doctors and trial physicians will together care for the patient; then the
patients will be briefed about the aim, objective and details of the procedure of the study.
If without capacity, their relatives will be approached about the trial and seek their
consent for recruitment. As this study will be confined into a tertiary care hospital,
patients will be recruited up to day 4 of illness.
Consenting participants: It will be prioritized that the patients will be treated early for
COVID-19 management by standard regiment and in accordance to the guidance of the national
guidelines. And within shortest possible time preferably within 4 hours of admission,
consenting procedure will be completed either from the patient or from the attendant/legal
guardian of the patients to obtain the full potential benefit of the treatment. Written
informed consent will be obtained from the patient in their own language [Bengali] by trial
physicians working on the trial.
Screening for eligibility: During admission, demographic and clinical details including name,
age/date of birth, gender, duration of onset of fever and hospitalization, vital statistics
will be recorded before randomization. RT PCR for COVID-19 will be used for confirmation of
the COVID-19 virus infection. A screening log will be maintained including these essential
details and the decision taken by the patient or attendant or legal guardian where
appropriate concerning recruitment. Ineligible and non-recruited patients will also be cared
by the ward physicians following standard treatment guidelines.
Procedure of randomization: The study participants will be randomly assigned in this study
into six equal groups; where each group has equal opportunity to receive any treatment
option. Randomization will be done by block randomization methods. Randomization will be done
quickly, with baseline information typically captured in <15 min. Recruitment & randomization
will be performed contemporaneously with assessment/resuscitation of patients by a second
person so that medical care is not delayed by recruitment. Patients will only be randomized
once baseline data has been entered; after this has been done, participants will not be
withdrawn from the study. Following completion of the randomization, the trial physicians
reported the Principal Investigator (PI) of the trial and then the Principal Investigator
(PI) handed over an opaque sealed envelope, which will be numbered sequentially to correspond
to patient enrollment numbers, which will be used for concealment of treatment allocations.
Envelopes will be kept in a locked drawer and will be opened in strictly numerical order by
in supervisor in presence of nursing supervisor of study unit. Allocation between arms will
initially be equal, although this may be revised following guidance of the PI and his team
(as per the statistical plan).
Withdrawal of study participants: Participants are free to withdraw from the study at any
point, for any reason. If this occurs, the primary reason for withdrawal will be documented
in the participant's case record form. The participant will have the option of withdrawal
from:
participant samples. Randomized patients who wish to withdraw from the study before they have
undertaken any study-related procedures will be replaced. Data on the original participant
will be kept on the CRF/database if the participant agrees to this.
Investigational medicinal products:
All of the Participants will be divided into three groups: Group A will receive Povidone
iodine (PVP-I) nasal irrigation (NI) at three different concentration of 0.4%, Group B and
Group C will received 0.5% and 0.6%; Group D will receive PVP-I nasal spray (NS) at
concentration of 0.5% and Group E will received at 0.6% concentration. Group F (Placebo
comparator group) will receive nasal irrigation by distilled water and Group G (Placebo
comparator group) will received nasal spray by distilled water Participant compliance: The
study team will not create any problem with compliance while the patient is under care and
supervision in hospital. It was ensured that all recruited patients receive the appropriate
interventions, although it could be interrupted due to the onset of potential adverse effects
such as hypotension.
Responsibility sharing of care of the patients: As the patients will remain under the care of
the hospitals' consultant physicians/unit head who will have primary responsibility for their
management. Management protocols will be agreed between the medical team and study team.
Decisions about intubation, requirement of blood and blood products, transfer of patients to
intensive care, weaning of ventilation and extubation will be made by the medical team
independently of study doctors. All decisions will be based on the patient's clinical
condition and the available hospital resources, as per usual hospital practice. The study
team preferably by trial physicians will note down the record in patient's Case Record Form
(CRF).
Methods of data collection: data collection will be done by the trial physicians. A paper
based semi-structured questionnaire was made and pre-tested before data collection. All
potential participants will be recorded in this database at first contact and assigned a
study number. This study number (eg DMC-PVP-I-0001) will be used for all data and samples
collected from that person. Study doctors will recruit and randomize patients at the bedside
with a randomization procedure. They will not be able to predict allocation before
randomization. Following randomization, allocation will be done by the PI and trial
physicians or nurse will confirm the administration of the either drug/distilled water.
Patients will be closely monitored. Temperature will be measured in every 6 hours, blood
pressure, respiratory rate, pulse rate will be measured in every hour. Urine output will be
measured in every 8 hours. Drug related side effects or any adverse events will be observed
in each group.
If there is no reaction or unusual event, another RT-PCR sample will be collected from the
nasopharynx and sent for further testing.
Total duration of the follow up will be for 2 days (or person fulfills the discharge
criteria). All clinical events will be noted in case record form by trial physicians,
including vital status at hospital discharge. Data entry will be date/time stamped.
Laboratory analysis data will be collected using same CRF.
Data quality and standards: following collection, all data set and collected record form will
be checked. A formal clinical data management plan will be written before the study starts,
agreed by the co-investigators, and Data Monitoring Committee, and documented trail master
file. Laboratory results will be discussed regularly between the PI and laboratory managers.
Proposed Analysis Plan of the study:
Data analysis will be done by data management software, R-4.0.2'. Statistical significance is
set as 95% confidence level at 5% acceptable error level. Differences will be considered
significant at the P < 0.05 level for all these tests. The data will be expressed as means
±Standard deviations (SD) for continuous variables and as frequencies (%) for categorical
variables. Chi-square test, student t test or ANOVA or other statistical test will be used in
case of normally distributed data and similar non-parametric data will be used whenever
appropriate. Graph & chart will be expressed by Microsoft Excel 2016.
Ethical consideration:
The researcher is duly concern about the ethical issues relate to the study. In this study
the following criteria will be followed to ensure maintaining the ethical values. All ethical
measure will be followed in accordance to the current Declaration of the Helsinki and Good
clinical practice (GCP) and Good laboratory practice (GLP) guidelines.
Facilities available at study center:
The RT-PCR and other study-related testing will be done at DMCH. DMCH was designated as a
COVID dedicated hospital which provide multidisciplinary care.Necessary investigations are
available here with minimal cost.
