The Sisonke Phase 3 b study resumes on Wednesday 28 April 2021
Cape Town | The Sisonke investigators would like to update health workers and the public regarding the pause on vaccinations, review of safety data and actions taken to ensure vaccination resumes as quickly as possible.
Rare clotting syndrome: An extremely rare condition characterised by blood clots in the presence of low platelets – a component of your bloodstream that assists with clotting and the prevention of bleeding – was first described in March following administration of the AstraZeneca-Oxford vaccine in the United Kingdom and Europe. People affected by it have presented with unusual blood clots in large veins draining the brain (cerebral venous sinus thrombosis) and abdomen (splanchnic vein thrombosis). A similar clinical picture was initially reported in 6 people following vaccination of 6.8 million people with the JnJ (COVID-19 Vaccine Janssen) vaccine in the US rollout. A further 2 cases have since been reported in the USA, bringing that total to 8. No cases have been described South Africa yet. This condition, now known as Vaccine-Induced Thrombotic Thrombocytopenia or VITT (referring to clots and low platelets), has been recognised as an extremely rare complication of both the AstraZeneca-Oxford and JnJ vaccines. No information regarding its occurrence after the Sputnik V vaccine, also a viral vector vaccine, is available. VITT typically presents with new onset severe and unrelenting headache 4 to 20 days post vaccination. In these people, it can be rapidly diagnosed using a widely available blood test. Treatment differs from the usual therapies for clotting problems and should be undertaken in consultation with a specialist haematologist with experience managing a similar disorder that sometimes occurs following a commonly used blood thinner called heparin. The European Medicines Agency, South African Health Product Regulatory Authority (SAHPRA) and US Food and Drug Administration have all called for vaccination with the JnJ vaccine to recommence emphasising that the benefits of protection against severe COVID-19 infection far outweigh the risk of this rare side-effect.
Actions taken by the Sisonke investigators to mitigate this risk include widespread public and participant (both past and future) communication, education of vaccinator staff and health workers, revised screening protocols, enhanced safety monitoring and inclusion of experts in extremely rare side-effects such as VITT and anaphylaxis (a severe form of allergy) who will work with local site researchers and clinicians to ensure optimal management should these events occur. While we note that the number of cases was too low to make any generalisations regarding risk, we have introduced enhanced screening processes and consultation with our safety team for all participants with a history of a severe or chronic clotting condition. In addition, vaccine recipients will be sent two additional SMS reminders 1 and 2 weeks after their vaccination prompting them to seek care if they develop any symptoms including new-onset severe headache, weakness on one side, difficulty speaking, severe abdominal pain, swelling or pain in one leg, shortness of breath or chest pain, or blood spots around the site of injection. We remind clinicians that the Sisonke Desk is available tollfree 24 hours a day 7 days a week. Should a clinician be concerned about a suspected case of VITT, we will assign a safety doctor and haematology expert to help guide treatment. We invite concerned members of the public and media to an information webinar hosted by the Desmond Tutu Health Foundation on the 4th of May at 12 noon. Registration is available at: http://bit.ly/DTHFVaccines3.
Sisonke restart and new exclusion of breastfeeding women: We welcomed the news on 21st April that Cabinet wishes to resume the Sisonke trial and vaccination of our health workers ahead of the third wave. On the 23rd April SAHPRA gave approval to return to the field with an amended protocol. The protocol has been amended to augment safety and oversight in the case of VITT. SAHPRA has also requested that pregnant and breastfeeding women not be vaccinated under the Sisonke study.
We acknowledge that safety data for COVID-19 vaccines in pregnancy and breastfeeding are limited and still accumulating. International and local experts and groups such as the College of Obstetricians and Gynaecologists of South Africa, the World Health Organization, the International Federation of Obstetrics and Gynaecologists, the US CDC, the United Kingdom’s Joint Committee on Vaccination and Immunisation, the American College of Obstetrics and Gynaecology and the Royal College of Obstetricians and Gynaecologists have remained united in strongly recommending vaccination for pregnant and breastfeeding women given large amounts of safety data for similar ‘‘non-live’ vaccines. Pregnancy exposure safety data for >100,000 exposed pregnancies for other ‘non-live’ vaccines including seasonal influenza and tetanus, diphtheria, pertussis and poliomyelitis polyvalent vaccines show no safety concerns. Animal studies for mRNA and the JnJ vaccine showed no concerns, and the Ebola vaccine, which uses the same adenovirus vector as the JnJ vaccine, has been used widely including pregnant women with no concerns. It is therefore considered highly unlikely that such vaccines would be harmful if administered in pregnancy or breastfeeding. We welcome last week the publication of the preliminary safety data on the safety profile of m-RNA vaccines in pregnant women in the United States showing no safety concerns and note the recommendation that pregnant women be offered a m-RNA vaccine. However, as per SAHPRA approval, pregnant and breastfeeding women will not be included in the Sisonke study.
Breastfeeding health workers: To health workers who have already received the vaccine while breastfeeding, please do not be concerned. COVID-19 vaccines are not able to replicate in the human body, disintegrate within 2-3 days of vaccination, and do not pass into breastmilk. Breastfeeding women have been included in all trials of the JnJ vaccine thus far, with no safety concerns reported in mothers or their infants. If you still have concerns we ask that you be in touch with the Sisonke Desk through this link: https://is.gd/sisonke_ae.
Sisonke vaccination set to resume Wednesday 28 April: We have taken all necessary precautions and preparations to resume vaccination for non-pregnant and non-breastfeeding health workers so that we can deliver the 200 000 doses of JnJ we have at hand to ensure we protect half a million health workers before the third wave. Site staff have been briefed and all participant information updated. Unvaccinated and registered health workers will be re-invited to read and provide their consent for participation in the last phase of the Sisonke trial. We are working closely with our colleagues in the National and Provincial Departments of Health to ensure a smooth transition to the rest of Phase 1 and Phase 2 national roll out.
NOTE TO THE EDITOR:
About the Sisonke Study:
The Sisonke study is a collaboration between the National Department of Health, South African Medical Research Council, Desmond Tutu Health Foundation, CAPRISA, Janssen and Johnson & Johnson. This open label, single-arm Phase 3b vaccine clinical trial of the investigational single-dose Janssen COVID-19 vaccine candidate aims to monitor the effectiveness of the investigational single-dose Janssen vaccine candidate at preventing severe COVID-19, hospitalizations and deaths among healthcare workers as compared to the general unvaccinated population in South Africa.