| Protocol No: | ECCT/20/07/01 | Date of Protocol: | 12-09-2020 |
| Study Title: | A randomized control trial comparing convalescent plasma therapy plus standard treatment versus standard treatment alone in patients with severe COVID-19 pneumonia at a tertiary hospital |
| A randomized control trial comparing convalescent plasma therapy plus standard treatment versus standard treatment alone in patients with severe COVID-19 pneumonia at a tertiary hospital
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| No amendment | |
| Study Objectives: | Primary Objective
TTCI is defined as the time (in days) from initiation of study treatment (active or standard care) until a decline of two categories from admission status on a six-category ordinal scale of Clinical status which ranges from 1 (discharged) to 6 (death).
Six-category ordinal scale: 6. Death 5. ICU, requiring IMV; 4. ICU/hospitalization, requiring NIV/ HFNC therapy; 3. Hospitalization, requiring supplemental oxygen (but not NIV/ HFNC); 2. Hospitalization, not requiring supplemental oxygen; 1. Hospital discharge. Abbreviation: IMV, invasive mechanical ventilation; NIV, non-invasive mechanical ventilation; HFNC, High-flow nasal cannula.
Secondary objectives
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| 1 | 1 Primary Objective To evaluate safety of convalescent plasma therapy in patients with severe Covid-19. To evaluate efficacy of convalescent plasma therapy with standard treatment versus standard treatment alone with respect to time to clinical improvement (TTCI) [Time Frame: up to 28 days]. TTCI is defined as the time (in days) from initiation of study treatment (active or standard care) until a decline of two categories from admission status on a six-category ordinal scale of Clinical status which ranges from 1 (discharged) to 6 (death). Six-category ordinal scale: 6. Death; 5. ICU, requiring IMV; 4. ICU/hospitalization, requiring NIV/ HFNC therapy; 3. Hospitalization, requiring supplemental oxygen (but not NIV/ HFNC); 2. Hospitalization, not requiring supplemental oxygen; 1. Hospital discharge. Abbreviation: IMV, invasive mechanical ventilation; NIV, non-invasive mechanical ventilation; HFNC, High-flow nasal cannula. Secondary objectives To compare duration of severe illness, based on SOFA score, between patients enrolled in the intervention and control groups assessed by the ordinal scale on days 7, 14, 21, and 28. To compare the proportion of patients requiring oxygen supplementation between the intervention and control groups up to 28 days. To compare the proportion of patients on mechanical ventilation between the intervention and control groups up to 28 days. To determine the mean PaO2/FiO2 between the intervention and control groups up to 28 days. To determine time to negative SARS-COV2 RT-PCR test in respiratory tract specimens between the intervention and control groups up to 28 days To determine the length of ICU stay(days) between the intervention and control groups up to 28 days. To determine length of hospital stay (days) between the intervention and control groups up to 28 days. To determine all-cause mortality between the intervention and control groups up to 28 days. |
| 2 | Primary Objective a) To evaluate safety of convalescent plasma therapy in patients with severe COVID-19. b) To evaluate efficacy of convalescent plasma therapy with standard treatment versus standard treatment alone with respect to time to clinical improvement (TTCI) [Time Frame: up to 28 days]. TTCI is defined as the time (in days) from initiation of study treatment (active or standard care) until a decline of two categories from admission status on a six category ordinal scale of Clinical status which ranges from 1 (discharged) to 6 (death) (42). Six-category ordinal scale: 6. Death 5. ICU, requiring IMV; 4. ICU/hospitalization, requiring NIV/ HFNC therapy; 3. Hospitalization, requiring supplemental oxygen (but not NIV/ HFNC); 2. Hospitalization, not requiring supplemental oxygen; 1. Hospital discharge. Abbreviations: IMV, invasive mechanical ventilation; NIV, non-invasive mechanical ventilation; HFNC, High-flow nasal cannula. Secondary objectives a) To compare duration of severe illness, based on SOFA score, between patients enrolled in the intervention and control groups assessed by the ordinal scale on days 7, 14, 21, and 28. b) To compare the proportion of patients requiring oxygen supplementation between the intervention and control groups up to 28 days. c) To compare the proportion of patients on mechanical ventilation between the intervention and control groups up to 28 days. d) To determine the mean PaO2/FiO2 between the intervention and control groups up to 28 days. e) To determine time to negative SARS-COV2 RT-PCR test in respiratory tract specimens between the intervention and control groups up to 28 days f) To determine the length of ICU stay(days) between the intervention and control groups up to 28 days. g) To determine length of hospital stay (days) between the intervention and control groups up to 28 days. h) To determine all-cause mortality between the intervention and control groups up to 28 days. i) To determine the effect of SARS-COV-2 viral strain on CP treatment effectiveness. |
| Laymans Summary: | COVID 19 pandemic is caused by a virus called SARS COV2 that was first identified in Wuhan, China in December 2019. So far, there is no effective treatment or vaccine for the virus. As of 13 June 2020, there are over 7 million reported cases in the world and Kenya had 3457 reported cases and 100 deaths. Use of plasma from patients who have recovered from various viruses to enhance the immunity of those with the virus and help them fight it has shown promising results. However, this has only been demonstrated in small case reports. We plan to use a filtration device, Hemoclear, to separate plasma from blood donated by COVID 19 recovered patients and then give this plasma to COVID 19 patients showing signs and symptoms of severe disease to help them fight the disease and ensure quick recovery. Studies have shown patients with COVID 19 usually have developed enough antibodies by day 15 of the disease. Using statistics, we need atleast 206 patients randomly assigned to the group of convalescent plasma and standard treatment to show any difference between the 2 groups. Only group specific and infection free blood will be used. This study will happen at Kenyatta University Teaching Referral and Research hospital |
| 1 | Covid-19 pandemic is as a result of a virus called SARS-COV2 which is contagious and primarily spreds through air or contact with contaminated surfaces.There is no effective treatment or vaccine as of now. Even though a majority of people (upto 80%) have no symptoms or have mild disease, 5-15% develop severe to critical illness requiring ICU admission. Plasma, which is a component of blood, from patients who have recovered from various viral infections such as spanish flu, H1N1, ebola, Middle East respiratory syndrome (MERS) etc has been used as a treatment in the past with good results and it was found to be safe. This plasma is referred to as convalescent plasma. Since patients with severe to critical Covid-19 are at an increased risk of death, convalescent plasma from patients who have just recovered from Covid-19 and have no symptoms can help them fight the disease by boosting their immunity. This study will compare patients with standard treatment for severe Covid-19 plus convalescent plasma to those receiving standard treatment alone as specified in the national guidelines. The main objective will be to look at how safe is convalescent plasma and also see whether patients recover faster with this treatment. All safety precautions surrounding donating and transfusing blood will be followed. This study will enrol 103 patients with severe Covid-19 per group. |
| 2 | No amendments |
| Abstract of Study: | Background: Covid-19 pandemic is as a result of infection with SARS-COV2. There are no effective antiviral drugs and no vaccines yet making use of convalescent plasma therapy reasonable. Objectives: The primary objective of this study is to evaluate safety and efficacy of convalescent plasma therapy plus standard treatment versus standard treatment alone in patients with severe Covid-19 disease. Trial design: Randomized open label controlled trial Sample size: 103 experimental group and 103 control group Participants: Adults aged >18yrs who meet inclusion criteria and give informed written consent to donate whole blood at least 14 days after initial disease with 2 negative RT-PCR for SARS-COV2 and are asymptomatic. The whole blood with be filtered by a gravity driven microfiltration device, Hemoclear into plasma and packed cells. Recipients of convalescent plasma will be adults >18yrs old who meet inclusion criteria and have severe Covid-19 disease. Intervention and comparator: Standard treatment for Covid-19 plus 350mls of convalescent plasma transfused over 4 hours compared with standard treatment alone Outcomes. The primary outcome will be to evaluate adverse events and time to clinical improvement as defined by WHO ordinal scale between experimental group and control group. Secondary outcomes will include comparing duration of length of ICU stay, duration of mechanical ventilation, duration of hospital stay, oxygen requirements, rate of turning negative SARS-COV2 test and all-cause mortality in 28 days between the experimental therapy and control therapy. Trial status: Approved by PPB Trial registration: Pan African Clinical Trials Registry (PACTR202007653923168). |
| 1 | Background: Covid-19 pandemic is as a result of infection with SARS-COV2. There are no effective antiviral drugs and no vaccines yet making use of convalescent plasma therapy reasonable. Objectives: The primary objective of this study is to evaluate safety and efficacy of convalescent plasma therapy plus standard treatment versus standard treatment alone in patients with severe Covid-19 disease. Trial design: Randomized open label controlled trial Sample size: 103 experimental group and 103 control group Participants: Adults aged >18yrs who meet inclusion criteria and give informed written consent to donate whole blood at least 14 days after initial disease with 2 negative RT-PCR for SARS-COV2 and are asymptomatic. The whole blood with be filtered by a gravity driven microfiltration device, Hemoclear into plasma and packed cells. Recipients of convalescent plasma will be adults >18yrs old who meet inclusion criteria and have severe Covid-19 disease. Intervention and comparator: Standard treatment for Covid-19 plus 350mls of convalescent plasma transfused over 4 hours compared with standard treatment alone Outcomes. The primary outcome will be to evaluate adverse events and time to clinical improvement as defined by WHO ordinal scale between experimental group and control group. Secondary outcomes will include comparing duration of length of ICU stay, duration of mechanical ventilation, duration of hospital stay, oxygen requirements, rate of turning negative SARS-COV2 test and all-cause mortality in 28 days between the experimental therapy and control therapy. Trial status: Awaiting PPB approval Trial registration: Pan African Clinical Trials Registry (PACTR202007653923168). |
| 2 | No amendment |