Ministry of Health Malaysia starts Ivermectin trial for high risk COVID-19 patients (I-TECH Study)
Effective pharmacologic treatments for COVID-19 remains a challenge. The Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial showed dexamethasone, a steroid, improved mortality outcomes for COVID-19 patients in severe stage of disease when oxygen supplementation or mechanical ventilation is required. But for the management of mild and moderate cases, there is lack of treatment, either to prevent disease progression or cut viral transmission.
The COVID-19 clinical characterisation study by MOH specialists and researchers found that for cases admitted to hospitals, 95% had mild illness but about 3.5% subsequently progressed to severe disease. They were mostly of older age (≥51 years) or had underlying co-morbidities such as chronic kidney disease and chronic pulmonary disease that increased their risk for severe disease. However, for high-risk COVID-19 patients, many repurposed antiviral therapies were found ineffective. The World Health Organization (WHO) COVID-19 Solidarity Trial for COVID-19 Treatments (SOLIDARITY) which included Malaysia, found insufficient evidence for the use of remdesivir, hydroxychloroquine, interferon, lopinavir in terms of mortality outcomes. Currently, the Malaysian Consensus Management Guidelines for COVID-19 maintains Favipiravir, as the only antiviral therapy for the management of COVID-19 cases. Even this recommendation may change as more evidence becomes available.
Ivermectin is an FDA-approved anti-parasitic drug widely used for treating several neglected tropical diseases, including onchocerciasis, strongyloidiasis and helminthiases. The “off-label” use of Ivermectin gained global attention due to some promising results by case studies and clinical trials. Yet, the evidence is inconclusive to recommend routine use of Ivermectin for COVID-19. The FDA has not approved Ivermectin for use in treating or preventing Covid-19 in humans, and the WHO only recommends the use of Ivermectin in the setting of clinical trials, in which patients are monitored closely by experienced clinicians and researchers for safety and efficacy. There is an on-going need for adequately powered, well-designed, and well-conducted clinical trials for evidence-based guidance on the role of Ivermectin in the treatment of COVID-19.
Under the circumstances, the Ministry of Health Malaysia and the Institute for Clinical Research (ICR) have initiated a multicentre open-label randomized controlled trial. The Ivermectin Treatment Efficacy in Covid-19 High Risk Patients (I-TECH Study) headed by Infectious Disease (ID) Physician at Hospital Raja Permaisuri Bainun, Ipoh and a team of specialists and Clinical Research Centres (CRC) at 12 MOH hospitals. The trial was approved by Medical Research and Ethics Committee (MREC), MOH on 25 May 2021. The study compares Ivermectin treatment (specific dose with specific duration) with the standard of care alone. The study will enrol 500 subjects from high risk groups aged 50 years and above admitted to MOH hospitals with mild/moderate COVID-19 symptoms (Stage 2-3). The study aims to determine the efficacy of Ivermectin in preventing the progression of COVID-19 to severe disease (Stage 4-5) and in terms of mortality outcomes. ICR has setup a Data Monitoring Board (DMB) consisting of independent ID physicians, clinical trial pharmacists and methodological experts to safeguard the trial patients on the safety and efficacy of the investigation product set by the National Pharmaceutical Regulatory Agency (NPRA).
According to MOH, the First-Patient-In (FPI) was on 31 May 2021, and to date 8 patients have been enrolled. The study is expected to be completed by September 2021.
Contacts and Locations (ClinicalTrials.gov)
Contacts:
CHEE L LIM, MRCP; 6013-3620081; stevenlimcl@gmail.com
Mohan D Pathmanathan, MD; 6012-9190794; mohan.pathmanathan@gmail.com
Locations:
Sultanah Aminah Hospital
80000 Johor Bahru, Johor, Malaysia
Contact: Masliza Zaid, MRCP
Sultanah Bahiyah Hospital
Alor Setar, Kadah, Malaysia, 05460
Contact: Lee L Low, MRCP
Sultan Abdul Halim Hospital
Sungai Petani, Kedah, Malaysia, 08000
Contact: Noralfazita An@Amran, MRCP
Hospital Raja Permaisuri Bainun, Ipoh
Ipoh, Perak, Malaysia, 30450
Contact: Hong B Ker, MRCP
Taiping Hospital
Taiping, Perak, Malaysia, 34000
Contact: Wooi K Cheah, MRCP
Tuanku Fauziah Hospital
Kangar, Perlis, Malaysia, 01000
Contact: Suhaila Ab Wahab, MRCP
Pulau Pinang Hospital
George Town, Pulau Pinang, Malaysia, 10990
Contact: Ting S Chow, MRCP
Lahad Datu Hospital
Tawau, Sabah, Malaysia, 911000
Contact: Song W Khoo, MRCP
Sarawak General Hospital
Kuching, Sarawak, Malaysia, 93586
Contact: Han H Lim, MRCP
Sungai Buloh Hospital
Shah Alam, Selangor, Malaysia, 47000
Contact: Kim H Tay, MRCP
Kuala Lumpur Hospital
Kuala Lumpur, Malaysia, 50586
Contact: Khairil E Khalid, MRCP
Melaka Hospital
Melaka, Malaysia, 754000
Contact: Nor Zaila Zaidan, MRCP
The off-label use of Ivermectin to treat COVID-19 is only for clinical trials
The Health Ministry has denied a viral message claiming that they are allowing usage of the anti-parasitic drug Ivermectin to treat Covid-19 upon request by patients in hospitals.
"The off-label use of Ivermectin to treat Covid-19 is only for clinical trials – not on the request of patients in hospital," it said in a Facebook post on Saturday (July 10).
The post claimed that the Ministry was allowing the use of Ivermectin for those who ask for it.
There is evidence that vitamin C and quercetin co-administration exerts a synergistic antiviral action due to overlapping antiviral and immunomodulatory properties and the capacity of ascorbate to recycle quercetin, increasing its efficacy.
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The COVID-19 clinical characterisation study by MOH specialists and researchers found that for cases admitted to hospitals, 95% had mild illness but about 3.5% subsequently progressed to severe disease. They were mostly of older age (≥51 years) or had underlying co-morbidities such as chronic kidney disease and chronic pulmonary disease that increased their risk for severe disease. However, for high-risk COVID-19 patients, many repurposed antiviral therapies were found ineffective. The World Health Organization (WHO) COVID-19 Solidarity Trial for COVID-19 Treatments (SOLIDARITY) which included Malaysia, found insufficient evidence for the use of remdesivir, hydroxychloroquine, interferon, lopinavir in terms of mortality outcomes. Currently, the Malaysian Consensus Management Guidelines for COVID-19 maintains Favipiravir, as the only antiviral therapy for the management of COVID-19 cases. Even this recommendation may change as more evidence becomes available.
Ivermectin is an FDA-approved anti-parasitic drug widely used for treating several neglected tropical diseases, including onchocerciasis, strongyloidiasis and helminthiases. The “off-label” use of Ivermectin gained global attention due to some promising results by case studies and clinical trials. Yet, the evidence is inconclusive to recommend routine use of Ivermectin for COVID-19. The FDA has not approved Ivermectin for use in treating or preventing Covid-19 in humans, and the WHO only recommends the use of Ivermectin in the setting of clinical trials, in which patients are monitored closely by experienced clinicians and researchers for safety and efficacy. There is an on-going need for adequately powered, well-designed, and well-conducted clinical trials for evidence-based guidance on the role of Ivermectin in the treatment of COVID-19.
Under the circumstances, the Ministry of Health Malaysia and the Institute for Clinical Research (ICR) have initiated a multicentre open-label randomized controlled trial. The Ivermectin Treatment Efficacy in Covid-19 High Risk Patients (I-TECH Study) headed by Infectious Disease (ID) Physician at Hospital Raja Permaisuri Bainun, Ipoh and a team of specialists and Clinical Research Centres (CRC) at 12 MOH hospitals. The trial was approved by Medical Research and Ethics Committee (MREC), MOH on 25 May 2021. The study compares Ivermectin treatment (specific dose with specific duration) with the standard of care alone. The study will enrol 500 subjects from high risk groups aged 50 years and above admitted to MOH hospitals with mild/moderate COVID-19 symptoms (Stage 2-3). The study aims to determine the efficacy of Ivermectin in preventing the progression of COVID-19 to severe disease (Stage 4-5) and in terms of mortality outcomes. ICR has setup a Data Monitoring Board (DMB) consisting of independent ID physicians, clinical trial pharmacists and methodological experts to safeguard the trial patients on the safety and efficacy of the investigation product set by the National Pharmaceutical Regulatory Agency (NPRA).
According to MOH, the First-Patient-In (FPI) was on 31 May 2021, and to date 8 patients have been enrolled. The study is expected to be completed by September 2021.
Contacts:
CHEE L LIM, MRCP; 6013-3620081; stevenlimcl@gmail.com
Mohan D Pathmanathan, MD; 6012-9190794; mohan.pathmanathan@gmail.com
Locations:
Sultanah Aminah Hospital
80000 Johor Bahru, Johor, Malaysia
Contact: Masliza Zaid, MRCP
Sultanah Bahiyah Hospital
Alor Setar, Kadah, Malaysia, 05460
Contact: Lee L Low, MRCP
Sultan Abdul Halim Hospital
Sungai Petani, Kedah, Malaysia, 08000
Contact: Noralfazita An@Amran, MRCP
Hospital Raja Permaisuri Bainun, Ipoh
Ipoh, Perak, Malaysia, 30450
Contact: Hong B Ker, MRCP
Taiping Hospital
Taiping, Perak, Malaysia, 34000
Contact: Wooi K Cheah, MRCP
Tuanku Fauziah Hospital
Kangar, Perlis, Malaysia, 01000
Contact: Suhaila Ab Wahab, MRCP
Pulau Pinang Hospital
George Town, Pulau Pinang, Malaysia, 10990
Contact: Ting S Chow, MRCP
Lahad Datu Hospital
Tawau, Sabah, Malaysia, 911000
Contact: Song W Khoo, MRCP
Sarawak General Hospital
Kuching, Sarawak, Malaysia, 93586
Contact: Han H Lim, MRCP
Sungai Buloh Hospital
Shah Alam, Selangor, Malaysia, 47000
Contact: Kim H Tay, MRCP
Kuala Lumpur Hospital
Kuala Lumpur, Malaysia, 50586
Contact: Khairil E Khalid, MRCP
Melaka Hospital
Melaka, Malaysia, 754000
Contact: Nor Zaila Zaidan, MRCP
"The off-label use of Ivermectin to treat Covid-19 is only for clinical trials – not on the request of patients in hospital," it said in a Facebook post on Saturday (July 10).
The post claimed that the Ministry was allowing the use of Ivermectin for those who ask for it.
Ivermectin and FLCCC
In October 2020, FLCCC (Front Line COVID-19 Critical Care) Alliance added ivermectin as a core medication in the prevention and treatment of COVID-19. FLCCC regard ivermectin as a core medication in the prevention and treatment of COVID-19. For comprehensive information on ivermectin please refer to their Review of the Emerging Evidence Supporting the Use of Ivermectin in the Prophylaxis and Treatment of COVID-19 and the included references.
In addition, check out the evidence tracker on Ivermectin versus COVID-19 from Ivmmeta.com (constantly updated).
FLCCC (Front Line COVID-19 Critical Care) Protocol
The initial MATH+ protocol was released in April 2020. In early July and August, it was updated to include quercetin and a number of optional nutrients and drugs, not only for critical care but also for prophylaxis and mild disease being treated at home (I-MASK+ protocol).
There is evidence that vitamin C and quercetin co-administration exerts a synergistic antiviral action due to overlapping antiviral and immunomodulatory properties and the capacity of ascorbate to recycle quercetin, increasing its efficacy.
For prevention, the Front Line COVID-19 Critical Care Working Group (FLCCC) recommends (updated June 30, 2021):The medical evidence to support each drug and nutrient can be found under “Medical Evidence” on the FLCCC’s website.
- Vitamin D3: 1000–3000 IU/day. Note RDA (Recommended Daily Allowance) is 800–1000 IU/day. The safe upper-dose daily limit is likely < 4000 IU/day. Vitamin D deficiency has been associated with an increased risk of acquiring COVID-19 and from dying from the disease. Vitamin D supplementation may therefore prove to be an effective and cheap intervention to lessen the impact of this disease, particularly in vulnerable populations, i.e. the elderly and obese. (Lazada)
- Vitamin C: 500 - 1,000 mg BID (twice daily) (Lazada)
- Quercetin: 250 mg daily. It is likely that vitamin C and quercetin have synergistic prophylactic benefit. Quercetin should be used with caution in patients with hypothyroidism and TSH levels should be monitored. (Lazada)
- Melatonin: 6 mg before bedtime (causes drowsiness). (Lazada)
- Zinc: 30 - 40 mg/day (elemental zinc). Zinc lozenges are preferred. (Lazada)
- Ivermectin for
- prevention in high-risk individuals (> 60 years with co-morbidities, morbid obesity, long term care facilities, etc): 0.2 mg/kg per dose (take with or after meals) — one dose today, repeat after 48 hours, then one dose weekly.
- Post COVID-19 exposure prevention: 0.2 mg/kg per dose (take with or after meals) — one dose today, repeat after 48 hours.
Notes:
- Ivermectin has a number of potentially serious drug-drug interactions. Please check for potential drug interaction at Ivermectin Drug Interactions - Drugs.com. The most important drug interactions occur with cyclosporin, tacrolimus, anti-retroviral drugs, and certain anti-fungal drugs.
- Due to the possible drug interaction between quercetin and ivermectin (may increase ivermectin levels), these drugs should not be taken simultaneously (i.e. should be staggered morning and night).
- Ivermectin is also lipophilic and therefore, bioavailability is maximised on a full stomach; or best to be taken with meal.
For early outpatient protocol (COVID-19 positive), the Front Line COVID-19 Critical Care Working Group, FLCCC recommends (updated June 30, 2021):
- Vitamin D3 — 4000 IU/day. (Lazada)
- Vitamin C: 500 - 1,000 mg BID (twice daily) (Lazada)
- Quercetin: 250 mg twice a day. (Lazada)
- Melatonin: 10 mg before bedtime (causes drowsiness). (Lazada)
- Zinc: 100 mg/day. Zinc lozenges are preferred. (Lazada)
- Ivermectin: 0.2–0.4 mg/kg per dose (take with or after meals) — one dose daily, take for 5 days or until recovered.
- Fluvoxamine (Luvox): 50 mg twice daily for 10–14 days. Add to ivermectin if: 1) minimal response after 2 days of ivermectin; 2) in regions with more aggressive variants; 3) treatment started on or after day 5 of symptoms or in pulmonary phase; or 4) numerous co-morbidities/risk factors. Avoid if patient is already on an SSRI (selective serotonin reuptake inhibitor).
- Nasopharyngeal Sanitation: Steamed essential oil inhalation 3 times a day (i.e. vapo-rub) and/or chlorhexidine/benzydamine mouthwash gargles (Lazada) and Betadine nasal spray 2–3 times a day (Lazada).
- Aspirin: 325 m/day unless contraindicated. (Lazada)
- Pulse Oximeter: FLCCC also recommend monitoring your oxygen saturation with a pulse oximeter and to go to the hospital if you get below 94%. (Lazada)
Notes:
- Optional: Curcumin: 400 mg twice a day for treatment and once a day for maintenance (Ref) (Lazada)
- Duration for supplements: Most supplements (e.g. vitamin D, zinc, quercetin) for early treatment are given for 5 - 10 days. To continue for preventive purposes, dosages will need to be reduced as per the prevention or prophylaxis protocol.
- If you can’t get fluvoxamine (Luvox), using 30mg once a day of fluoxetine (Prozac) is equally effective (equivalent to 50mg twice a day of fluvoxamine).
Summary
Be aware that most of the 'treatment' dosages for supplements are above the recommended dietary allowance (RDA) and therefore such dosages should NOT be maintained on a long term basis.
Disclaimer: Always see your doctor before taking any supplements or medications. This info-article is provided as a public service. In no event shall we or our affiliates be liable for any special, incidental or consequential damages arising out of or in connection with this information or website, including negligence.
You still need to follow the advice given by WHO and your local authority in terms of local guidelines such as face mask wearing, social distancing, vaccination and avoiding crowds. There is unlikely to be any single magic bullet strategy. It's better to combine multiple strategies in order to reduce your risk and defend yourself against this virus.
Note: COVID-19 is a highly dynamic topic. Please refer to the latest FLCCC protocol (June 30, 2021 version).
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