South African National Clinical Trials Registry
South African Medical Research Council, Cochrane South Africa
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: sactradmin@mrc.ac.za Website: sanctr.samrc.ac.za
Trial no.: DOH-27-032024-8873 Date of Approval: 13/03/2024
Trial Status: Approved
TRIAL DESCRIPTION
Public title A MULTI-CENTRE, DOUBLE-BLIND, RANDOMISED, PARALLEL GROUP, CONTROLLED STUDY TO PROVIDE RELIABLE EVIDENCE OF THE EFFICACY OF THE AFRICAN TRADITIONAL HERBAL MEDICINE, PHELA, AS AN ADJUNCT THERAPY IN ADULT PATIENTS WITH LONG‑TERM EFFECTS OF COVID‑19 WHO DEVELOP FIRST-EPISODE NON‑DRUG RESISTANT PULMONARY TUBERCULOSIS
Official scientific title A MULTI-CENTRE, DOUBLE-BLIND, RANDOMISED, PARALLEL GROUP, CONTROLLED STUDY TO PROVIDE RELIABLE EVIDENCE OF THE EFFICACY OF THE AFRICAN TRADITIONAL HERBAL MEDICINE, PHELA, AS AN ADJUNCT THERAPY IN ADULT PATIENTS WITH LONG‑TERM EFFECTS OF COVID‑19 WHO DEVELOP FIRST-EPISODE NON‑DRUG RESISTANT PULMONARY TUBERCULOSIS
Brief summary describing the background and objectives of the trial PHELA is a herbal preparation containing four African traditional medicinal plants (Gladiolus dalenii, Senna occidentalis, Rotheca myriciodes and Clerodendrum glabrum) that have been used for decades to treat wasting conditions and for increasing energy in patients who were weak and wasted. PHELA has recently been reported to benefit immune compromised individuals as an immune stimulant. There have been voluntary observational studies submitted to the Indigenous Knowledge Systems (IKS) Health Division and anecdotal reports of patients having benefited from using this medication have also been received. These findings, supported by pathology laboratory results, have been reported to the IKS by a number of independent medical practitioners who have been working with traditional practitioners in the management of over 1000 HIV-positive and AIDS patients. The mechanism of action of PHELA is yet to be fully described. However, in preliminary research performed in rats, it was found that PHELA stimulates or restores Cyclosporine-induced immune suppression indicating possible Interleukin-2 (IL-2) activation. Some immune stimulation studies are ongoing, looking at the effects of PHELA in Cytokine Immune Stimulation, specifically at the stimulation of IL-2, IL-8 and Tumour Necrosis Factor (TnF). Experiments were also conducted in animals to evaluate the anti-viral activity of PHELA. The effect of PHELA on Reverse transcriptase, Protease and Integrase enzymes were also briefly studied. It was found that the different plant extracts of PHELA have very good activity in the inhibition of these enzymes, but more research is proposed. Primary Objective To evaluate the efficacy of Long-COVID treatment and pTB SoC plus PHELA compared to Long-COVID treatment and pTB SoC plus PHELA-placebo as an adjunct therapy in adult patients presenting with long-term effects of COVID-19 and confirmed drug sensitive TB disease per SA NTCP requirements who develops first episode non-drug resistant pTB.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) Phela
Disease(s) or condition(s) being studied Infections and Infestations,Long-COVID
Sub-Disease(s) or condition(s) being studied Tuberculosis
Purpose of the trial Treatment: Other
Anticipated trial start date 03/07/2023
Actual trial start date
Anticipated date of last follow up 31/07/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 516
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
PHELA post COVID Sponsor
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Sealed opaque envelopes Masking/blinding used Care giver/Provider,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Phela Placebo 2 x placebo capsules Twice daily 6 to 7 months Long-COVID treatment AND pTB SoC PLUS PHELA-placebo (2 x placebo capsules b.i.d [12 hourly]) for at least 6 months/7 months 258 Placebo
Experimental Group Phela 350mg 2 x 350mg capsules Twice daily 6 to 7 months Long-COVID treatment AND pTB SoC PLUS PHELA (2 x 350 mg capsules b.i.d [12 hourly]) for at least 6 months/7 months (per SA NTCP requirements) 258
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Written consent given for participation in the study. 2. Non-hospitalised males and females, ≥ 18 years at the screening visit. 3. Body weight of at least 50 kg at screening. 4. Patients with a history of and/or documented confirmation of previous acute COVID-19 infection presenting with COVID-19-associated symptoms persisting ≥ 3 months after the acute COVID-19 infection, including, but not limited to: fever or chills, shortness of breath or difficulty breathing, cough, fatigue, muscle or body aches, headache, new loss of taste, new loss of smell, blocked or runny nose, nausea, vomiting or diarrhoea. 5. Patients presenting with pulmonary TB disease symptoms and subsequently confirmed drug-sensitive first-episode pulmonary TB disease as per the South African National TB Control Programme (NTCP) requirements. 6. Patients with chronic comorbidities (e.g., hypertension, diabetes mellitus) adequately controlled through lifestyle and/or treatment may be enrolled in the study at the discretion of the site investigator. 7. Laboratory investigations (i.e., full blood count, clinical chemistry, D-Dimer, and urinalysis) within acceptable ranges at the discretion of the site investigator. 8. Acceptable physical examination findings at the discretion of the site investigator. 9. Estimated Glomerular Filtration Rate (eGFR) > 60 mL/min. 10. Women of childbearing potential and non-childbearing potential will be included. A woman will be considered of non-childbearing potential if she has been surgically sterilized, undergone a hysterectomy, has amenorrhea for ≥ 12 months and is considered post-menopausal. 11. Patients willing to use the prescribed treatment (this includes treatment prescribed for pulmonary TB and for COVID-19-related symptoms persisting ≥ 3 months after the acute COVID-19 infection) and the experimental treatment (PHELA or PHELA-placebo), and who are willing to follow the site investigator’s and study staff’s instructions. 1. Patient currently using PHELA or who used PHELA within 7 days prior to enrolment in the study. 2. Patients who developed symptoms more than 96 hours (4 days) before Screening. 3. Known allergy to any of the constituents of PHELA. 4. Contra-indications to PHELA or treatments for Long-COVID and/or pTB. 5. Need for or use of antiviral medications at the time of screening for any viral pathology, except antiretroviral medication for HIV/AIDS. 6. Patients participating in another clinical study. 7. Patients with multidrug-resistant tuberculosis (MDR TB) and extensively drug-resistant TB (XDR TB). 8. Patients with any other concomitant acute infectious disease, at the discretion of the site investigator. 9. Patients using oxygen at home. 10. Intake of an investigational drug or biologic in another study within 3 months or within 5 half-lives (whichever is longer) before administration of treatment in this study. 11. Employees or close relatives of the contract research organisation, the sponsor, 3rd party vendors or affiliates of the above-mentioned parties. Adult: 19 Year(s)-105 Year(s) 18 Year(s) 105 Year(s) Both
APPROVALS
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 07/06/2023 SAMAREC
Ethics Committee Address
Street address City Postal code Country
Block F, Castle Walk Office Park, Nossob Street, Erasmuskloof, Ext 3, Pretoria, 0181 Pretoria 0181 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 27/11/2023 SAHPRA
Ethics Committee Address
Street address City Postal code Country
CSIR Reception Building 38a Meiring Naudé Road Brummeria Pretoria Pretoria 0083 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Time to AFB-negative sputum smear Weeks 2 to 12
Secondary Outcome Change over time in cumulative 0-x signs/symptoms score Day 1, weeks 2 to 12 and between week 25 and 29
Secondary Outcome Change over time in cumulative 0-x quality-of-life score Day 1, weeks 2 to 12 and between week 25 and 29
Secondary Outcome Change over time in measured blood-based biomarkers (as indicators of immunomodulation) Screening, day 1, 28, 56, 84, 161 and between weeks 25 to 29
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
FCRN Clinical Trial Centre Orwell Place 3, Orwell Drive Three Rivers Vereeniging 1935 South Africa
Prohealth Wellness Clinic Suite 27 B, Ziyabuya complex KwaDwesi Port Elizabeth 6201 South Africa
Trident Clinical 12 Angel Street New Park Kimberley 8301 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
University of the Free State 205 Nelson Mandela drive Bloemfontein 9301 South Africa
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of the Free State 205 Nelson Mandela Drive Bloemfontein 9301 South Africa University
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Christopher Mushwana dr.chris@ctcvaal.co.za +27734870620 Orwell Park 3 Orwell Drive Three Rivers
City Postal code Country Position/Affiliation
Vereeniging 1935 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator Lungisa Excel Nojoko doctor@ppmresearch.co.za +27727860207 Suite 27 B Ziyabuya Complex
City Postal code Country Position/Affiliation
KwaDwesi Port Elizabeth 6201 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator Clementina Duran Palma c.palma@tridentclinical.co.za +27721415649 12 Angel Street
City Postal code Country Position/Affiliation
New Park Kimberley 8301 South Africa Principal Investigator
Role Name Email Phone Street address
Public Enquiries Motlalepula Matsabisa matsabisamg@ufs.ac.za +27514017452 205 Nelson Mandela
City Postal code Country Position/Affiliation
Bloemfontein 9301 South Africa Sponsor
Role Name Email Phone Street address
Scientific Enquiries Motlalepula Matsabisa MatsabisaMG@ufs.ac.za +27514017452 205 Nelson Mandela
City Postal code Country Position/Affiliation
Bloemfontein 9301 South Africa Sponsor
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes At the end of the clinical study, the Sponsor may publish the study results in scientific journal(s). As part of the review for publication, independent scientists may need to use “coded” data of all the study participants to independently verify the study’s results. In addition, results from clinical trials in participants are required to be submitted to peer-reviewed journals following internal company review for accuracy, fair balance and intellectual property. For those journals that request sharing of the analyzable data sets that are reported in the publication, interested researchers are directed to submit their request to vivli.org. Analytic Code,Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol For pediatric and adult trials, the results will generally be submitted/released 6 and 12 months respectively, after the end of the clinical trial worldwide (ie, the last active, participating country). Sanofi shares information about clinical trials and results on publicly accessible websites, based on company commitments, international and local legal and regulatory requirements, and other clinical trial disclosure commitments established by pharmaceutical industry associations. These websites include ClinicalTrials.gov, euclinicaltrials.eu, and sanofi.com, as well as some national registries. Individual anonymized participant data and supporting clinical documents are available for request at vivli.org. While making information available we continue to protect the privacy of participants in our clinical trials. Details on data sharing criteria and process for requesting access can be found at this web address: vivli.org.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information