Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000386730
Ethics application status
Approved
Date submitted
2/03/2022
Date registered
4/03/2022
Date last updated
22/11/2022
Date data sharing statement initially provided
4/03/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Therapies to prevent progression of COVID-19 in outpatients: The 'Primary Care Australian COVID-19 Therapeutics' (PACT) Trial
Scientific title
Therapies to prevent progression of COVID-19, including Ivermectin, Doxycycline, Vitamin C, Vitamin D, and Zinc with or without Famotidine: a randomised placebo-controlled double-blind multi-centre outpatient trial
Secondary ID [1] 306521 0
Nil
Universal Trial Number (UTN)
Trial acronym
PACT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19 325394 0
Condition category
Condition code
Infection 322783 322783 0 0
Other infectious diseases
Respiratory 322784 322784 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
2 trial arms:
1) Ivermectin, Doxycycline, Vitamin C, Vitamin D3 and Zinc
2) Ivermectin, Doxycycline, Vitamin C, Vitamin D3 and Zinc plus Famotidine

with the following daily doses for 10 days:
Arm 1+2:
Ivermectin 12 mg twice daily
Doxycycline 100mg twice daily
Vitamin C (1 gm thrice daily)
Vitamin D3 (10,000iu midday daily)
Zinc picolinate (50 mg elemental midday daily)

plus - Arm 2 only:
Famotidine (Histamine H2 receptor antagonist) 40mg twice daily for 10 days

Therapy packs are dispensed as ten days supply (at daily dosing), to be administered as one tablet and one capsule three times daily for ten days.

Arm 1: Core Therapy - 20 capsules containing (ivermectin 12mg, doxycycline 100mg), vitamin-C 1g (30 tablets), 10 capsules containing (vitamin D3 10000iu, zinc picolinate 50mg).

Arm 2: Core Therapy & Famotidine - 20 capsules containing (ivermectin 12mg, doxycycline 100mg, famotidine 40mg), vitamin-C 1g (30 tablets), 10 capsules containing (vitamin D3 10000iu, zinc picolinate 50mg).

The morning and evening therapy (containing ivermectin) is to be consumed with a fatty meal prepared by the participant's at their own discretion.
Both intervention and control groups will be able to make contact with the Trial Research Nurse at any time. Compliance will be checked daily by verbal confirmation with the trial nurse.
Intervention code [1] 322949 0
Treatment: Drugs
Comparator / control treatment
No Famotidine in the comparator group .
Both groups receive Ivermectin, Doxycycline, Vitamin C, Vitamin D3 and Zinc.
In both groups, outcomes will be compared to population data on outcomes of standard care without Ivermectin, Doxycycline, Vitamin C, Vitamin D3 and Zinc.
Control group
Active

Outcomes
Primary outcome [1] 330577 0
The primary outcome of this trial is hospital admission.
Hospital admission is defined as the requirement to receive inpatient care for a COVID-19 related illness.
This can include short stay emergency department admission, hospital in the home (HITH) admission/care, general medical admission, intensive care admission.
Assessed by data linkage to patient medical records
Timepoint [1] 330577 0
daily for 15 days since enrolment
Secondary outcome [1] 406747 0
Composite: Duration and severity of symptoms by daily online specifically designed questionnaire filled in by the trial nurse
Timepoint [1] 406747 0
daily by trial nurse/doctor on days 1-10, and 28 since start of symptoms
Secondary outcome [2] 406749 0
oxygen saturation levels, assessed by daily online diary
Timepoint [2] 406749 0
daily by trial nurse/doctor on days 1-10, and 28 since start of symptoms
Secondary outcome [3] 406750 0
oxygen supplementation needs, assessed by data linkage to patient medical records
Timepoint [3] 406750 0
daily by trial nurse/doctor on days 1-10, and 28 since start of symptoms
Secondary outcome [4] 406751 0
healthcare provider contacts assessed by trial nurse/ doctor contact
Timepoint [4] 406751 0
daily by trial nurse/doctor on days 1-10, and 28 since start of symptoms
Secondary outcome [5] 406752 0
requirement for additional antibiotics or other therapies since start of symptoms assessed by telephone follow-up by trial nurse/ doctor contact
Timepoint [5] 406752 0
daily by trial nurse/doctor on days 1-10, and 28 since start of symptoms
Secondary outcome [6] 406753 0
WHO-5 Wellbeing Index by online questionnaire
Timepoint [6] 406753 0
day 10 and 28 since enrolment since start of symptoms
Secondary outcome [7] 406754 0
requirement of mechanical ventilation, assessed by data linkage to patient medical records
Timepoint [7] 406754 0
daily by trial nurse/doctor on days 1-10, and 28 since start of symptoms
Secondary outcome [8] 406755 0
death, assessed by data linkage to patient medical records
Timepoint [8] 406755 0
daily by trial nurse/doctor on days 1-10, and 28 since start of symptoms

Eligibility
Key inclusion criteria
• COVID-19 diagnosis in the preceding 4 days (RAT positive or PCR positive)
• At least 40 years old
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Women who are pregnant, breastfeeding or actively trying to achieve a pregnancy
• Current hospital inpatient with COVID-19 related disease
• Allergy to ivermectin, doxycycline or famotidine
• Known bleeding disorder
• Known severe liver disease
• Diagnosis of Myasthenia Gravis/SLE
• Consumption of grapefruit juice
• Ever travelled to countries that are endemic for Loa loa (West and Central Africa – Angola, Cameroon, Central African Republic, Democratic Republic of Congo, Ethiopia, Guinea, Gabon, Republic of Congo, Nigeria and Sudan)
• Currently on the following medications:
o Cardiac - quinidine, amiodarone, diltiazem, verapamil, warfarin
o Anti-infective – clarithromycin, erythromycin, itraconazole, ketoconazole,
o Anti-viral – indinavir, ritonavir, cobicistat
o Disease modifying – cyclosporine, tacrolimus, sirolimus, methotrexate
o Other – retinoids, lithium, spironlactone

Neither minority groups nor NESB/LOTE persons will be excluded provided they possess the capacity (ie ability to understand, retain, comprehend and dutifully consider a response) to consent.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Trial medication will be packaged in identical blister packs by centralised pharmacy.
After written consent is obtained, a ‘script’ will be written for the participant (including random study number) by the Trial General Practitioner. The pharmacist after obtaining the written prescription will allocate the next ‘treatment’ as per the random allocation sheet.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be according to computer-generated variable block randomisation by a researcher not involved with patient recruitment and treatment.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Stage 1: Minimum total sample size required is N=300, or N=150 in each trial arm in order to adequately explore the benefit.
During the conduct of the trial, we may need to make adjustments to several aspects of study design. To enable this and to monitor safety, the trial data will be reviewed periodically by an expert and independent data safety monitoring board (DSMB).

All analysis will be by intention to treat and per protocol. Statistical analyses of the data will be performed by the investigators with external support as required. This analysis will be undertaken blinded to therapy arms.

Data will be summarized according to epidemiological and clinical risk factors and other baseline characteristics, clinical presentation, and outcome appropriate summary statistics. The first step of the analysis will be to assess the adequacy of the randomisation process by comparing demographics of each of the arms of the PACT Trial. If important imbalances exist, multivariate analysis may be required. Statistical analysis will be by intention to treat and per protocol for all outcome measures.
Categorical data will be analysed using chi-squared and presented as relative risks. Student-t test will be used for data presented on a continuous scale, including the WHO-5 Wellbeing Index. Subgroup analyses will be undertaken including: if previously vaccinated (with or without booster status), day of illness on therapy initiation, participant age and BMI.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
28/03/2022
Actual
26/04/2022
Date of last participant enrolment
Anticipated
31/03/2023
Actual
Date of last data collection
Anticipated
28/04/2023
Actual
Sample size
Target
300
Accrual to date
44
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 310865 0
Charities/Societies/Foundations
Name [1] 310865 0
Lumina Medical Research
Country [1] 310865 0
Australia
Primary sponsor type
Individual
Name
AProf Dr Karin Ried
Address
National Institute of Integrative Medicine
21 Burwood Rd
Hawthorn VIC 3122
Country
Australia
Secondary sponsor category [1] 312126 0
None
Name [1] 312126 0
Address [1] 312126 0
Country [1] 312126 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310427 0
National Institute of Integrative Medicine Human Research Ethics Committee (NIIM HREC)
Ethics committee address [1] 310427 0
National Institute of Integrative Medicine
21 Burwood Rd
Hawthorn VIC 3122
Ethics committee country [1] 310427 0
Australia
Date submitted for ethics approval [1] 310427 0
08/02/2022
Approval date [1] 310427 0
07/03/2022
Ethics approval number [1] 310427 0
0099N_2022

Summary
Brief summary
COVID-19 is a global pandemic and has limited cost-effective early treatments. There is some evidence that the use of Vitamin C, Vitamin D and Zinc may be of benefit in conjunction with Ivermectin and Doxycycline. The second phase of the illness is inflammatory and it is possible that Famotidine may help this phase and reduce people needing hospitalisation.
This randomised multi-centre outpatient trial aims to ascertain whether therapy with Ivermectin, Doxycycline, Vitamin C, Vitamin D, and Zinc with or without Famotidine reduces hospitalisation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 117630 0
Dr Lucas McLindon
Address 117630 0
Gynaecology & Fertility
537 Stanley St
South Brisbane QLD 4101
Country 117630 0
Australia
Phone 117630 0
+61 7 3379 8676
Fax 117630 0
Email 117630 0
[email protected]
Contact person for public queries
Name 117631 0
Dr Lucia Grace Murnane
Address 117631 0
General Practitioner
National Institute of Integrative Medicine
PO Box 6070
Hawthorn VIC 3122
Country 117631 0
Australia
Phone 117631 0
+61 490 441 911
Fax 117631 0
Email 117631 0
[email protected]
Contact person for scientific queries
Name 117632 0
Dr Bruce Wauchope
Address 117632 0
Molechecks Australia
Bedford Medical Clinic
1284 South Road
Clovelly Park
South Australia SA 5042
Country 117632 0
Australia
Phone 117632 0
+61 407 607 092
Fax 117632 0
Email 117632 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.