Ignite Creation Date:
2024-05-06 @ 3:19 PM
Last Modification Date:
2024-10-26 @ 1:47 PM
Study NCT ID:
NCT04597775
Status:
UNKNOWN
Last Update Posted:
2020-10-22
First Post:
2020-10-18
Brief Title:
Chemoprevention Clinical Trial of COVID-19 Hydroxychloroquine Post Exposure Prophylaxis
Sponsor:
Regional Center for Disease Control and Prevention Jordan
Organization:
Regional Center for Disease Control and Prevention Jordan
Study Overview
Official Title:
A Prospective Randomized Adaptive Phase IIIII Clinical Trial Controlled Open-label 3-arms Parallel Multi-centred Chemoprevention of COVID-19 Hydroxychloroquine Post Exposure Prophylaxis For COVID-19
Status:
UNKNOWN
Status Verified Date:
2020-10
Last Known Status:
NOT_YET_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
APCC-19
Brief Summary:
Protocol summary
Title
A Prospective randomized adaptive phase IIIII clinical trial controlled open-label chemoprevention 3-arms parallel multi-centred to A Prospective randomized clinical trial controlled open-label 3-arms parallel multi-centred chemoprevention of COVID-19 Hydroxychloroquine Post Exposure Prophylaxis For COVID-19
Study Periods Duration of Treatment
Study Duration 6 months
Approval IRB and regulatory bodies 1 month
Recruitment and follow-up 3 months
Analysis report writing and submission of publications 1 month This study is a parallel study of one period with an expected duration of treatment for each subject of 28 days
Objectives
To evaluate if hydroxychloroquine with the proposed dose can provide potent chemoprophylaxis against the development of COVID-19 positive patients in subjects who had primary exposure to COVID-19 positive patients
To measure the incidence of potential adverse drug reaction rates for giving hydroxychloroquine for prevention of COVID-19 amongst close contacts
To provide early analysis of results and redefine sample size accordingly
identifying subjects most likely to benefit during the phase II and focusing recruitment efforts on them during phase III
stopping one arm or the whole trial at an early stage for success or lack of efficacy based on phase II study results
Design
Prospective Randomized open-label three-arm parallel adaptive phase IIIII controlled study in which subjects will be randomly assigned in a 111 ratio as per the following
Arm-1 hydroxychloroquine 800mg 400mg twice daily given orally on day 1 loading dose hydroxychloroquine Then 400mg 200mg 2 tablets on day 23 4 and 5
Arm-2 hydroxychloroquine 400mg 200mg twice daily Given orally first day loading dose then 200mg once daily on day 23 4 and 5
Arm-3 No Intervention- SARS-CoV-2 surveillance Standard control measures in the country of interest such as self isolation good personal hygiene and good nutrition
Title
A Prospective randomized adaptive phase IIIII clinical trial controlled open-label chemoprevention 3-arms parallel multi-centred to A Prospective randomized clinical trial controlled open-label 3-arms parallel multi-centred chemoprevention of COVID-19 Hydroxychloroquine Post Exposure Prophylaxis For COVID-19
Study Periods Duration of Treatment
Study Duration 6 months
Approval IRB and regulatory bodies 1 month
Recruitment and follow-up 3 months
Analysis report writing and submission of publications 1 month This study is a parallel study of one period with an expected duration of treatment for each subject of 28 days
Objectives
To evaluate if hydroxychloroquine with the proposed dose can provide potent chemoprophylaxis against the development of COVID-19 positive patients in subjects who had primary exposure to COVID-19 positive patients
To measure the incidence of potential adverse drug reaction rates for giving hydroxychloroquine for prevention of COVID-19 amongst close contacts
To provide early analysis of results and redefine sample size accordingly
identifying subjects most likely to benefit during the phase II and focusing recruitment efforts on them during phase III
stopping one arm or the whole trial at an early stage for success or lack of efficacy based on phase II study results
Design
Prospective Randomized open-label three-arm parallel adaptive phase IIIII controlled study in which subjects will be randomly assigned in a 111 ratio as per the following
Arm-1 hydroxychloroquine 800mg 400mg twice daily given orally on day 1 loading dose hydroxychloroquine Then 400mg 200mg 2 tablets on day 23 4 and 5
Arm-2 hydroxychloroquine 400mg 200mg twice daily Given orally first day loading dose then 200mg once daily on day 23 4 and 5
Arm-3 No Intervention- SARS-CoV-2 surveillance Standard control measures in the country of interest such as self isolation good personal hygiene and good nutrition
Detailed Description:
Type of study and design
Prospective Randomized open-label three-arm parallel controlled adaptive phase IIIII clinical trial in which subjects will be randomly assigned in a 111 ratio as per the following
Arm 1 Arm 2 Arm 3 Day 1 HCQ 400 mg twice daily HCQ 200 mg twice daily Standard measurements of the country until the end of the participation in the study Day 2 HCQ 400 mg once daily HCQ 200 mg once daily Day 3 HCQ 400 mg once daily HCQ 200 mg once daily Day 4 HCQ 400 mg once daily HCQ 200 mg once daily Day 5 HCQ 400 mg once daily HCQ 200 mg once daily
Amount needed Plaquenil 200mg 558 tables per protocol 42 tablets are needed as preserved supply total 600 tables
Randomisation Subjects who meet the eligibility criteria at the study locations will be invited to take part in the study
Participants will be randomly assigned to the treatment arms Index cases will be used for the assignment of contacts For example number 147 9 will be on arm 1 number 3 5 10etc will be in arm 2 number 26 8 etc will be in arm 3
All close contacts of the same index case will be allocated to the same arm This would allow more valid results through prevention of potential further exposure to the virus mainly for the control arms who are expected to have higher incidence of the disease
Blinding This clinical trial is open-label The study does not compare multiple medicinal products it also does not include the use of a placebo product as it is a Proamtic clinical trial
Study procedures and evaluations Baseline assessment
Medical history
Inquiry about previous history of G6PD
Check for contraindications
Vital signs
Physical examination
RT-PCR
IgM IgG AB for SARS-Cov-2
Hematology
Biochemistry
Urinalysis
Retinopathy
Pregnancy test
ECG
Retinopathy screening
During follow-up visits subjects will assessed for
Random glucose level
Vital signs
Assessment of study intervention adherence
Assessment of adverse events
ECG
Retinopathy screening Study schedule
Sampling technique
This adaptive phase IIIII clinical trial will be conducted in two sites in Tunisia The main study is planned in 2 sites in Tunisia
As soon as a new subject in identified heshe will be consented for reaching his contacts according to Eligibility criteria The research team within 48 hours of index case identification will call hisher contacts who fulfil below criteria for participation in the trial All potential participants will be tested using RT-PCR and IgM and IgG antibodies to rule out current or previous disease status Results will be obtained on the same day and before consenting for taking part in the study Subjects positive for COVID-19 will be referred to local authorities for treatment according to their protocols
We will follow multistage sampling technique in involved countries Samples will be stratified by gender and then follow simple random sampling process
Screening
Before carrying out any procedure in this study subjects will be provided subject information and consent form The study will be thoroughly explained and all questions will be answered to the satisfaction of the subject Subjects will be given enough time to think about their participation through and inquire about any detail that may influence the decision Consent procedure will be carried out by the clinical investigator delegated clinical staff Neither the investigator nor the study staff will coerce or unduly influence subjects to participate or to continue to participate against their will Prior to the subjects participation the subject will personally sign date the consent form along with one witness at least the principal investigator the principal investigator may delegate the clinical investigator to sign the ICF whenever needed
Enrollment Baseline All potential participants will be tested using RT-PCR and IgM and IgG antibodies to rule out current or previous disease status Results will be obtained on the same day and before consenting for taking part in the study Subjects positive for COVID-19 will be referred to local authorities for treatment according to their protocols
Only subjects eligible for this study will be enrolled Refer to section 5 for eligibility criteria
Informed consent demographics vital signs Medical History and contraindications physical examinationhematology KFT LFT urinalysisIgM and IgG antibodies for SARS-CoV-2 RT-PCR Pregnancy test ECG Retinopathy screening Blood Glucose dosing Adverse event review
During screening and follow-up visits subjects will be examined and vital signs will be taken with relevant medical history taken to determine the lack of contraindication of the use the IMP and the achievement of the inclusion criteria Laboratory evaluations Laboratory evaluations will be conducted as per Table 61 of visits and procedures elaborated on table 61
Safety considerations Methods and timing for assessing recording and analysing safety parameters Adverse events The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up At each contact with the subject the Clinical Investigator will seek information on adverse events by specific questioning and as appropriate by examination Information on all adverse events will be recorded immediately in the source document and also in the appropriate adverse event module of the case report form CRF
All adverse events occurring during the study period will be recorded The clinical course of each event will be followed until resolution stabilization or until it has been determined that the study treatment or participation is not the cause Serious adverse events that are still ongoing at the end of the study period will be followed up to determine the final outcome Any serious adverse event that occurs after the study period and is considered to be possibly related to the study treatment or study participation should be recorded and reported immediately
The AE report will include the intensity severity duration of the event It will also explain how the case was managed At the end of the study all records and follow up forms of AEsADRsSAEsSADRs will be enlisted in the final report
4 Discontinuation criteria 41 Participants premature termination
The reason for participants premature termination will be documented on the appropriate page of the CRF and specified which of the following possible reasons were responsible for the study premature termination
Serious Adverse Event SUSAR
Participants consent withdrawal
Inappropriate enrolment
Development of exclusion criterion
Protocol deviation as described below
Such as not taking study treatment on time or the prescribed dose more than one time
Decline PCR test at baseline or during the follow-up
Decline ECG or ophthalmoscopy exams
Migratedmoved from the study area
Lost to follow-up A lost to follow-up is any participant who completed all protocol specific procedures up to the administration of the investigational product or intervention but was then lost during the study period to any further follow-up with no safety information and no efficacy endpoint data ever became available
It is vital to collect safety data on any participant discontinued because of an AE or SAE In any case every effort must be made to undertake protocol-specified safety follow-up procedures If voluntary withdrawal occurs the participant should be asked to continue scheduled evaluations complete an end-of-study evaluation and be given appropriate care under medical supervision until the symptoms of any AE resolve or the participants condition becomes stable
5 Statistical considerations Following an adaptive seamless phase IIIII design assuming 60 efficacy an odds ratio of about 03 of hydroxychloroquine in reducing COVID-19 infections for primary contacts and reported secondary attack rate of 35 incidence amongst close contacts Liu Y etal 90 power a confidence level of 95 and 10 loss to follow-up 31 COVID-19 contacts are needed in each arm for phase II totaling 93 contacts for the three arms
The primary endpoints of this study are observed COVID-19 infection and observed ADRs Descriptive statistics including means frequencies and proportions will be used to summarize collected contacts data Incidence of the primary endpoints will be reported as well All summaries will be provided for the three study arms Chi-squared test will be used to compare incidence levels of the primary endpointsacross the three study arms To examine for associations among categorical contacts attributes Chi-squared and Fishers exact tests whenever appropriate will be usedWhen needed ANOVA will be used to test for significant differences among numerical attributesLogistic Regression techniques with stepwise selection method will be used to identify significant predictors of the primary endpoints Intention to treat analysis will be followed in this clinical trial
Data handling and record keeping Source documents and access to source data The Principal Investigators will maintain appropriate medical and research records for this study in compliance with the principles of good clinical practice and regulatory and institutional requirements for the protection of confidentiality of participants The study team members will have access to records
Authorised representatives of the sponsor the ethics committees or regulatory bodies may inspect all documents and records required to be maintained by the investigator for the purposes of quality assurance reviews audits inspections and evaluation of the study safety and progress This will include but not limited to medical records office clinic or hospital for the participants in this study The clinical study site will permit access to such records
Missing data will be reported as missing indicating the reasons where applicable
Protocol deviations A protocol deviation is any noncompliance with the clinical trial protocol good clinical practice GCP or other protocol-specific requirements
If a deviation from or a change of the protocol is implemented to eliminate an immediate hazards to trial participant without prior ethics approval the PI or designee will submit the implemented deviation or change the reasons for it and if appropriate the proposed protocol amendments as soon as possible to the relevant ethics committees for review and approval and to the sponsor for agreement
The PI or designee will document and explain any deviation from the approved protocol on the CRF where appropriate and record and explain any deviation in a file note or deviation form that will be maintained as an essential document
Deviations from the protocol GCP or trial specific requirements that might have an impact on the conduct of the trial or the safety of participants will be reported within 5 working days to the sponsor and relevant EC as appropriate
Ethical considerations The investigator will ensure that this study is conducted in full conformity with the principles set forth in the ICH Harmonised Tripartite Guideline for Good Clinical Practice and the Declaration of Helsinki in its current version whichever affords the greater protection to the participants
Rationale for participants election Study population will be males and females aged 18-65 years non-pregnant and non-lactating with primary exposure to COVID-19 patients The study is proposed to be conducted in Tunisia
Financing and insurance All subjects will be covered by insurance throughout the study and in case of an injury to health caused by the trial
Prospective Randomized open-label three-arm parallel controlled adaptive phase IIIII clinical trial in which subjects will be randomly assigned in a 111 ratio as per the following
Arm 1 Arm 2 Arm 3 Day 1 HCQ 400 mg twice daily HCQ 200 mg twice daily Standard measurements of the country until the end of the participation in the study Day 2 HCQ 400 mg once daily HCQ 200 mg once daily Day 3 HCQ 400 mg once daily HCQ 200 mg once daily Day 4 HCQ 400 mg once daily HCQ 200 mg once daily Day 5 HCQ 400 mg once daily HCQ 200 mg once daily
Amount needed Plaquenil 200mg 558 tables per protocol 42 tablets are needed as preserved supply total 600 tables
Randomisation Subjects who meet the eligibility criteria at the study locations will be invited to take part in the study
Participants will be randomly assigned to the treatment arms Index cases will be used for the assignment of contacts For example number 147 9 will be on arm 1 number 3 5 10etc will be in arm 2 number 26 8 etc will be in arm 3
All close contacts of the same index case will be allocated to the same arm This would allow more valid results through prevention of potential further exposure to the virus mainly for the control arms who are expected to have higher incidence of the disease
Blinding This clinical trial is open-label The study does not compare multiple medicinal products it also does not include the use of a placebo product as it is a Proamtic clinical trial
Study procedures and evaluations Baseline assessment
Medical history
Inquiry about previous history of G6PD
Check for contraindications
Vital signs
Physical examination
RT-PCR
IgM IgG AB for SARS-Cov-2
Hematology
Biochemistry
Urinalysis
Retinopathy
Pregnancy test
ECG
Retinopathy screening
During follow-up visits subjects will assessed for
Random glucose level
Vital signs
Assessment of study intervention adherence
Assessment of adverse events
ECG
Retinopathy screening Study schedule
Sampling technique
This adaptive phase IIIII clinical trial will be conducted in two sites in Tunisia The main study is planned in 2 sites in Tunisia
As soon as a new subject in identified heshe will be consented for reaching his contacts according to Eligibility criteria The research team within 48 hours of index case identification will call hisher contacts who fulfil below criteria for participation in the trial All potential participants will be tested using RT-PCR and IgM and IgG antibodies to rule out current or previous disease status Results will be obtained on the same day and before consenting for taking part in the study Subjects positive for COVID-19 will be referred to local authorities for treatment according to their protocols
We will follow multistage sampling technique in involved countries Samples will be stratified by gender and then follow simple random sampling process
Screening
Before carrying out any procedure in this study subjects will be provided subject information and consent form The study will be thoroughly explained and all questions will be answered to the satisfaction of the subject Subjects will be given enough time to think about their participation through and inquire about any detail that may influence the decision Consent procedure will be carried out by the clinical investigator delegated clinical staff Neither the investigator nor the study staff will coerce or unduly influence subjects to participate or to continue to participate against their will Prior to the subjects participation the subject will personally sign date the consent form along with one witness at least the principal investigator the principal investigator may delegate the clinical investigator to sign the ICF whenever needed
Enrollment Baseline All potential participants will be tested using RT-PCR and IgM and IgG antibodies to rule out current or previous disease status Results will be obtained on the same day and before consenting for taking part in the study Subjects positive for COVID-19 will be referred to local authorities for treatment according to their protocols
Only subjects eligible for this study will be enrolled Refer to section 5 for eligibility criteria
Informed consent demographics vital signs Medical History and contraindications physical examinationhematology KFT LFT urinalysisIgM and IgG antibodies for SARS-CoV-2 RT-PCR Pregnancy test ECG Retinopathy screening Blood Glucose dosing Adverse event review
During screening and follow-up visits subjects will be examined and vital signs will be taken with relevant medical history taken to determine the lack of contraindication of the use the IMP and the achievement of the inclusion criteria Laboratory evaluations Laboratory evaluations will be conducted as per Table 61 of visits and procedures elaborated on table 61
Safety considerations Methods and timing for assessing recording and analysing safety parameters Adverse events The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up At each contact with the subject the Clinical Investigator will seek information on adverse events by specific questioning and as appropriate by examination Information on all adverse events will be recorded immediately in the source document and also in the appropriate adverse event module of the case report form CRF
All adverse events occurring during the study period will be recorded The clinical course of each event will be followed until resolution stabilization or until it has been determined that the study treatment or participation is not the cause Serious adverse events that are still ongoing at the end of the study period will be followed up to determine the final outcome Any serious adverse event that occurs after the study period and is considered to be possibly related to the study treatment or study participation should be recorded and reported immediately
The AE report will include the intensity severity duration of the event It will also explain how the case was managed At the end of the study all records and follow up forms of AEsADRsSAEsSADRs will be enlisted in the final report
4 Discontinuation criteria 41 Participants premature termination
The reason for participants premature termination will be documented on the appropriate page of the CRF and specified which of the following possible reasons were responsible for the study premature termination
Serious Adverse Event SUSAR
Participants consent withdrawal
Inappropriate enrolment
Development of exclusion criterion
Protocol deviation as described below
Such as not taking study treatment on time or the prescribed dose more than one time
Decline PCR test at baseline or during the follow-up
Decline ECG or ophthalmoscopy exams
Migratedmoved from the study area
Lost to follow-up A lost to follow-up is any participant who completed all protocol specific procedures up to the administration of the investigational product or intervention but was then lost during the study period to any further follow-up with no safety information and no efficacy endpoint data ever became available
It is vital to collect safety data on any participant discontinued because of an AE or SAE In any case every effort must be made to undertake protocol-specified safety follow-up procedures If voluntary withdrawal occurs the participant should be asked to continue scheduled evaluations complete an end-of-study evaluation and be given appropriate care under medical supervision until the symptoms of any AE resolve or the participants condition becomes stable
5 Statistical considerations Following an adaptive seamless phase IIIII design assuming 60 efficacy an odds ratio of about 03 of hydroxychloroquine in reducing COVID-19 infections for primary contacts and reported secondary attack rate of 35 incidence amongst close contacts Liu Y etal 90 power a confidence level of 95 and 10 loss to follow-up 31 COVID-19 contacts are needed in each arm for phase II totaling 93 contacts for the three arms
The primary endpoints of this study are observed COVID-19 infection and observed ADRs Descriptive statistics including means frequencies and proportions will be used to summarize collected contacts data Incidence of the primary endpoints will be reported as well All summaries will be provided for the three study arms Chi-squared test will be used to compare incidence levels of the primary endpointsacross the three study arms To examine for associations among categorical contacts attributes Chi-squared and Fishers exact tests whenever appropriate will be usedWhen needed ANOVA will be used to test for significant differences among numerical attributesLogistic Regression techniques with stepwise selection method will be used to identify significant predictors of the primary endpoints Intention to treat analysis will be followed in this clinical trial
Data handling and record keeping Source documents and access to source data The Principal Investigators will maintain appropriate medical and research records for this study in compliance with the principles of good clinical practice and regulatory and institutional requirements for the protection of confidentiality of participants The study team members will have access to records
Authorised representatives of the sponsor the ethics committees or regulatory bodies may inspect all documents and records required to be maintained by the investigator for the purposes of quality assurance reviews audits inspections and evaluation of the study safety and progress This will include but not limited to medical records office clinic or hospital for the participants in this study The clinical study site will permit access to such records
Missing data will be reported as missing indicating the reasons where applicable
Protocol deviations A protocol deviation is any noncompliance with the clinical trial protocol good clinical practice GCP or other protocol-specific requirements
If a deviation from or a change of the protocol is implemented to eliminate an immediate hazards to trial participant without prior ethics approval the PI or designee will submit the implemented deviation or change the reasons for it and if appropriate the proposed protocol amendments as soon as possible to the relevant ethics committees for review and approval and to the sponsor for agreement
The PI or designee will document and explain any deviation from the approved protocol on the CRF where appropriate and record and explain any deviation in a file note or deviation form that will be maintained as an essential document
Deviations from the protocol GCP or trial specific requirements that might have an impact on the conduct of the trial or the safety of participants will be reported within 5 working days to the sponsor and relevant EC as appropriate
Ethical considerations The investigator will ensure that this study is conducted in full conformity with the principles set forth in the ICH Harmonised Tripartite Guideline for Good Clinical Practice and the Declaration of Helsinki in its current version whichever affords the greater protection to the participants
Rationale for participants election Study population will be males and females aged 18-65 years non-pregnant and non-lactating with primary exposure to COVID-19 patients The study is proposed to be conducted in Tunisia
Financing and insurance All subjects will be covered by insurance throughout the study and in case of an injury to health caused by the trial
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None