Chronic Kidney Diseases, COVID-19
Conditions
Keywords
Vaccine, CKD
Brief summary
This study is a 12-month, four-arm parallel-group randomized control trial of Pfizer-BioNTech versus MODERNA COVID-19 (Corona Virus disease 2019)vaccine boosters in chronic kidney disease and dialysis patients with poor humoral response following COVID-19 vaccination, in collaboration with 5 dialysis centers in Ontario and British Columbia, Canada . Patients will be randomized to MODERNA or Pfizer-BioNTech COVID-19 vaccine, they may have received either MODERNA or Pfizer-BioNTech COVID-19 vaccine for their initial two doses of vaccine, and will be stratified by their initial vaccine type (MODERNA or Pfizer-BioNTech ) prior to randomization, which will result in four study groups.
Detailed description
MODERNA : Nucleocapsid Modified messenger RNA BioNTech: Bio-Pharma new Technology
Interventions
BIOLOGICALPfizer-BioNTech COVID-19 Vaccine
This arm receives Pfizer-BioNTech COVID-19 Vaccine
BIOLOGICALMODERNA SARS-CoV-2 Vaccine
This arm receives MODERNA SARS-CoV-2 Vaccine
Sponsors
University Health Network, Toronto
Unity Health Toronto
Scarborough General Hospital
Providence Healthcare
Sunnybrook Health Sciences Centre
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with Chronic Kidney Disease (CKD)stage 3b-5 defined as an eGFR( estimated glomerular filtration rate ) of less than 45ml/min/1.73m2 or less will be eligible. Stage 5 CKD will include patients receiving in-center hemodialysis, home dialysis (home hemodialysis or peritoneal dialysis), vaccinated with two doses of the COVID-19 vaccine will be eligible for a third dose to be given 2-12 months following the second dose. * Age ≥18 at the time of study enrolment
Exclusion criteria
* Patients not vaccinated against COVID-19 vaccination. * Patients who received heterologous first two doses of vaccine * Patients with a severe allergic reaction to prior COVID-19 vaccination or any of the ingredients. * New COVID-19 infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Level of Anti-RBD ( Anti Receptor Binding Domain ) | One month | To measure Anti-Spike, Anti-NP antibodies, and SARS-CoV-2 specific neutralization at 1 month (30 days) following third dose of vaccine (BNT162b2 versus mRNA-1273) binding antibody levels for anti-receptor-binding domain and antispike IgG were reported as relative ratios to a synthetic standard included as a calibration curve on each assay plate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospitalization | 6 months | Number of participants who experienced COVID-19 related hospitalizations by study groups. |
| Proportion of B and T-cell Lymphocyte Subsets in Peripheral Blood Mononuclear Cells (PBMC) | 1 month | In a subset of participants, assess cellular immunity through flow cytometry on PBMC and single-cell RNA sequencing prior to, one month, and 6 months following vaccine booster. |
| Adverse Event | 14 days | Evaluate adverse events related to third dose of vaccine through a questionnaire within 48 hours to 14 days following third vaccine dose. |
| Serum Level of SARS-CoV-2 Antibodies | 3 months | To determine the effect of a third dose of COVID-19 vaccine on humoral immune response in hemodialysis patients through measurement of Anti-Spike, Anti-RBD, and Anti-NP antibodies at 3 months binding antibody levels for anti-receptor-binding domain and antispike IgG were reported as relative ratios to a synthetic standard included as a calibration curve on each assay plate. |
| COVID-19 Infections | 6 months | Number of participants who experienced COVID-19 infections and symptomatic COVID-19 infections. |
| Death | 6 months | Differences in death between study groups. Death was collected for 6 months following third dose (shorted from 12 months due to the introduction of the 4th dose). |
| Adverse Events (30 Days) | 1 month | Evaluate adverse events related to third dose of vaccine through a questionnaire at 30 days following third vaccine dose. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Third Dose BNT162b2 This group received BNT162b2 (Pfizer-BioNTech) as their third dose. | 137 |
| Third Dose mRNA-1273 This group received mRNA-1273 (Moderna) as their third dose | 136 |
| Total | 273 |
Baseline characteristics
| Characteristic | Third Dose BNT162b2 | Third Dose mRNA-1273 | Total |
|---|---|---|---|
| Age, Continuous | 71 years | 69 years | 70 years |
| Baseline two dose COVID-19 vaccine type BNT162b2 | 81 Participants | 81 Participants | 162 Participants |
| Baseline two dose COVID-19 vaccine type mRNA-1273 | 56 Participants | 55 Participants | 111 Participants |
| Cause of kidney disease Cystic kidney disease | 3 Participants | 7 Participants | 10 Participants |
| Cause of kidney disease Diabetes mellitus | 63 Participants | 63 Participants | 126 Participants |
| Cause of kidney disease Glomerulonephritis | 20 Participants | 26 Participants | 46 Participants |
| Cause of kidney disease Ischemic nephropathy | 34 Participants | 25 Participants | 59 Participants |
| Cause of kidney disease Other/unknown | 17 Participants | 15 Participants | 32 Participants |
| Comorbidities Active smoker | 7 Participants | 5 Participants | 12 Participants |
| Comorbidities Cerebrovascular disease | 8 Participants | 7 Participants | 15 Participants |
| Comorbidities Chemotherapy (3 mo) | 3 Participants | 2 Participants | 5 Participants |
| Comorbidities Chronic obstructive lung disease | 5 Participants | 10 Participants | 15 Participants |
| Comorbidities Congestive heart failure | 24 Participants | 17 Participants | 41 Participants |
| Comorbidities Coronary artery disease | 12 Participants | 19 Participants | 31 Participants |
| Comorbidities Hepatitis B nonresponder (HbsAb ,10 mIU/ml) | 52 Participants | 58 Participants | 110 Participants |
| Comorbidities Hypertension | 118 Participants | 112 Participants | 230 Participants |
| Comorbidities Immunosuppression | 3 Participants | 4 Participants | 7 Participants |
| Comorbidities Malignancy (prior 5 yr) | 9 Participants | 9 Participants | 18 Participants |
| Comorbidities Myocardial infarction | 17 Participants | 8 Participants | 25 Participants |
| Comorbidities Obesity (BMI $30 kg/m2) | 13 Participants | 15 Participants | 28 Participants |
| Comorbidities Peripheral vascular disease | 13 Participants | 7 Participants | 20 Participants |
| Comorbidities Solid organ transplant | 27 Participants | 19 Participants | 46 Participants |
| Comorbidities Type 1 diabetes mellitus | 6 Participants | 5 Participants | 11 Participants |
| Comorbidities Type 2 diabetes mellitus | 84 Participants | 72 Participants | 156 Participants |
| Days between COVID-19 vaccine doses, median First and second dose | 28 Days | 28 Days | 28 Days |
| Days between COVID-19 vaccine doses, median Second dose and third dose | 253 Days | 252 Days | 252 Days |
| Dialysis access Arteriovenous fistula or graft | 49 Participants | 48 Participants | 97 Participants |
| Dialysis access Central venous catheter | 78 Participants | 76 Participants | 154 Participants |
| Dialysis access PD catheter | 2 Participants | 4 Participants | 6 Participants |
| Dialysis modality Home hemodialysis | 5 Participants | 5 Participants | 10 Participants |
| Dialysis modality In-center hemodialysis | 122 Participants | 119 Participants | 241 Participants |
| Dialysis modality PD | 2 Participants | 4 Participants | 6 Participants |
| Dialysis vintage | 2.6 years | 2.6 years | 2.6 years |
| eGFR category 15-29 ml/min per 1.73 m2 | 1 Participants | 2 Participants | 3 Participants |
| eGFR category <15 ml/min per 1.73 m2 (nondialysis) | 2 Participants | 2 Participants | 4 Participants |
| eGFR category 30-44 ml/min per 1.73 m2 | 5 Participants | 4 Participants | 9 Participants |
| eGFR category Dialysis | 129 Participants | 128 Participants | 257 Participants |
| Nondialysis CKD participants - eGFR by CKD-EPI | 33 ml/min per 1.73 m2 | 31 ml/min per 1.73 m2 | 31 ml/min per 1.73 m2 |
| Nondialysis CKD participants - Microalbumin to creatinine ratio | 531 mg/mmol STANDARD_DEVIATION 692 | 725 mg/mmol STANDARD_DEVIATION 800 | 628 mg/mmol STANDARD_DEVIATION 729 |
| Prior COVID-19 infection COVID-19 hospitalization | 2 Participants | 1 Participants | 3 Participants |
| Prior COVID-19 infection COVID-19 intensive care unit admission | 1 Participants | 1 Participants | 2 Participants |
| Prior COVID-19 infection COVID-19 (RT-PCR confirmed) | 5 Participants | 3 Participants | 8 Participants |
| Prior COVID-19 infection Symptomatic COVID-19 | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian | 66 Participants | 67 Participants | 133 Participants |
| Race/Ethnicity, Customized Black or African origin | 10 Participants | 13 Participants | 23 Participants |
| Race/Ethnicity, Customized Missing | 10 Participants | 10 Participants | 20 Participants |
| Race/Ethnicity, Customized Other/multiracial | 18 Participants | 17 Participants | 35 Participants |
| Race/Ethnicity, Customized White | 33 Participants | 29 Participants | 62 Participants |
| Sex: Female, Male Female | 64 Participants | 57 Participants | 121 Participants |
| Sex: Female, Male Male | 73 Participants | 79 Participants | 152 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 17 / 137 | 9 / 136 |
| other Total, other adverse events | 82 / 129 | 89 / 126 |
| serious Total, serious adverse events | 23 / 137 | 16 / 136 |
Outcome results
Primary
Serum Level of Anti-RBD ( Anti Receptor Binding Domain )
To measure Anti-Spike, Anti-NP antibodies, and SARS-CoV-2 specific neutralization at 1 month (30 days) following third dose of vaccine (BNT162b2 versus mRNA-1273) binding antibody levels for anti-receptor-binding domain and antispike IgG were reported as relative ratios to a synthetic standard included as a calibration curve on each assay plate.
Time frame: One month
Population: 7 participants withdrew from each arm and were not included in analysis. Only participants who provided samples for this timepoint were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Third Dose BNT162b2 | Serum Level of Anti-RBD ( Anti Receptor Binding Domain ) | Anti-NP | 0.0630 relative ratio | Standard Deviation 0.334 |
| Third Dose BNT162b2 | Serum Level of Anti-RBD ( Anti Receptor Binding Domain ) | Anti-RBD | 0.807 relative ratio | Standard Deviation 0.416 |
| Third Dose BNT162b2 | Serum Level of Anti-RBD ( Anti Receptor Binding Domain ) | Anti-spike | 1.26 relative ratio | Standard Deviation 0.358 |
| Third Dose mRNA-1273 | Serum Level of Anti-RBD ( Anti Receptor Binding Domain ) | Anti-NP | 0.0415 relative ratio | Standard Deviation 0.169 |
| Third Dose mRNA-1273 | Serum Level of Anti-RBD ( Anti Receptor Binding Domain ) | Anti-RBD | 0.934 relative ratio | Standard Deviation 0.398 |
| Third Dose mRNA-1273 | Serum Level of Anti-RBD ( Anti Receptor Binding Domain ) | Anti-spike | 1.33 relative ratio | Standard Deviation 0.289 |
Secondary
Adverse Event
Evaluate adverse events related to third dose of vaccine through a questionnaire within 48 hours to 14 days following third vaccine dose.
Time frame: 14 days
Population: Population consists of only individuals who returned the completed survey.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Third Dose BNT162b2 | Adverse Event | Chills | 8 Participants |
| Third Dose BNT162b2 | Adverse Event | Myalgia | 15 Participants |
| Third Dose BNT162b2 | Adverse Event | Redness | 2 Participants |
| Third Dose BNT162b2 | Adverse Event | Arthralgia | 2 Participants |
| Third Dose BNT162b2 | Adverse Event | Fatigue | 17 Participants |
| Third Dose BNT162b2 | Adverse Event | Headache | 12 Participants |
| Third Dose BNT162b2 | Adverse Event | Pain | 67 Participants |
| Third Dose BNT162b2 | Adverse Event | Any symptom | 82 Participants |
| Third Dose BNT162b2 | Adverse Event | Nausea or vomiting | 6 Participants |
| Third Dose BNT162b2 | Adverse Event | Any severe symptom | 10 Participants |
| Third Dose BNT162b2 | Adverse Event | Swelling | 2 Participants |
| Third Dose BNT162b2 | Adverse Event | Any systemic symptom | 36 Participants |
| Third Dose BNT162b2 | Adverse Event | Diarrhea | 2 Participants |
| Third Dose BNT162b2 | Adverse Event | Antipyretic medication | 29 Participants |
| Third Dose BNT162b2 | Adverse Event | Fever (38°C) | 4 Participants |
| Third Dose mRNA-1273 | Adverse Event | Antipyretic medication | 42 Participants |
| Third Dose mRNA-1273 | Adverse Event | Fever (38°C) | 14 Participants |
| Third Dose mRNA-1273 | Adverse Event | Pain | 76 Participants |
| Third Dose mRNA-1273 | Adverse Event | Redness | 6 Participants |
| Third Dose mRNA-1273 | Adverse Event | Swelling | 9 Participants |
| Third Dose mRNA-1273 | Adverse Event | Chills | 19 Participants |
| Third Dose mRNA-1273 | Adverse Event | Fatigue | 30 Participants |
| Third Dose mRNA-1273 | Adverse Event | Nausea or vomiting | 10 Participants |
| Third Dose mRNA-1273 | Adverse Event | Diarrhea | 2 Participants |
| Third Dose mRNA-1273 | Adverse Event | Myalgia | 13 Participants |
| Third Dose mRNA-1273 | Adverse Event | Arthralgia | 5 Participants |
| Third Dose mRNA-1273 | Adverse Event | Headache | 15 Participants |
| Third Dose mRNA-1273 | Adverse Event | Any symptom | 89 Participants |
| Third Dose mRNA-1273 | Adverse Event | Any severe symptom | 12 Participants |
| Third Dose mRNA-1273 | Adverse Event | Any systemic symptom | 55 Participants |
Secondary
Adverse Events (30 Days)
Evaluate adverse events related to third dose of vaccine through a questionnaire at 30 days following third vaccine dose.
Time frame: 1 month
Population: We did not systematically collect symptoms at 30 days following vaccine dose, but rather 2-14 days only. This outcome was not analyzed.
Secondary
COVID-19 Infections
Number of participants who experienced COVID-19 infections and symptomatic COVID-19 infections.
Time frame: 6 months
Population: 7 participants withdrew from each arm
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Third Dose BNT162b2 | COVID-19 Infections | Confirmed cases of COVID-19 Infections with symptoms | 3 Participants |
| Third Dose BNT162b2 | COVID-19 Infections | Confirmed cases of COVID-19 Infections | 11 Participants |
| Third Dose mRNA-1273 | COVID-19 Infections | Confirmed cases of COVID-19 Infections | 15 Participants |
| Third Dose mRNA-1273 | COVID-19 Infections | Confirmed cases of COVID-19 Infections with symptoms | 10 Participants |
Secondary
Death
Differences in death between study groups. Death was collected for 6 months following third dose (shorted from 12 months due to the introduction of the 4th dose).
Time frame: 6 months
Population: excludes 7 participants that withdrew from each arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Third Dose BNT162b2 | Death | 17 Participants |
| Third Dose mRNA-1273 | Death | 9 Participants |
Secondary
Hospitalization
Number of participants who experienced COVID-19 related hospitalizations by study groups.
Time frame: 6 months
Population: 7 participants withdrew from each arm
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Third Dose BNT162b2 | Hospitalization | 1 Participants |
| Third Dose mRNA-1273 | Hospitalization | 2 Participants |
Secondary
Proportion of B and T-cell Lymphocyte Subsets in Peripheral Blood Mononuclear Cells (PBMC)
In a subset of participants, assess cellular immunity through flow cytometry on PBMC and single-cell RNA sequencing prior to, one month, and 6 months following vaccine booster.
Time frame: 1 month
Population: Analysis on this subset was not feasible following study completion. The collaborating laboratory was unable to logistically perform this testing due to the resources required for Flow Cytometry, and therefore this secondary outcome was not analyzed.
Secondary
Serum Level of SARS-CoV-2 Antibodies
To determine the effect of a third dose of COVID-19 vaccine on humoral immune response in hemodialysis patients through measurement of Anti-Spike, Anti-RBD, and Anti-NP antibodies at 3 months binding antibody levels for anti-receptor-binding domain and antispike IgG were reported as relative ratios to a synthetic standard included as a calibration curve on each assay plate.
Time frame: 3 months
Population: 7 participants withdrew from each arm and were not included in analysis. Only participants who provided samples for this timepoint were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Third Dose BNT162b2 | Serum Level of SARS-CoV-2 Antibodies | Anti-NP | 0.0985 relative ratios | Standard Deviation 0.424 |
| Third Dose BNT162b2 | Serum Level of SARS-CoV-2 Antibodies | Anti-RBD | 0.787 relative ratios | Standard Deviation 0.479 |
| Third Dose BNT162b2 | Serum Level of SARS-CoV-2 Antibodies | Anit-Spike | 1.14 relative ratios | Standard Deviation 0.389 |
| Third Dose mRNA-1273 | Serum Level of SARS-CoV-2 Antibodies | Anti-NP | 0.0665 relative ratios | Standard Deviation 0.178 |
| Third Dose mRNA-1273 | Serum Level of SARS-CoV-2 Antibodies | Anti-RBD | 0.941 relative ratios | Standard Deviation 0.499 |
| Third Dose mRNA-1273 | Serum Level of SARS-CoV-2 Antibodies | Anit-Spike | 1.24 relative ratios | Standard Deviation 0.36 |
Secondary
Serum Level of SARS-CoV-2 Antibodies
Determine the effect of a third dose of COVID-19 vaccine on humoral immune response in hemodialysis patients through measurement of Anti-Spike, Anti-RBD, and Anti-NP antibodies at 12 months
Time frame: 12 months
Population: Study was terminated before 12 months visit occurred.
Secondary
Serum Level of SARS-CoV-2 Antibodies
To determine the effect of a third dose of COVID-19 vaccine on humoral immune response in hemodialysis patients through measurement of Anti-Spike, Anti-RBD, and Anti-NP antibodies at 6 months binding antibody levels for anti-receptor-binding domain and antispike IgG were reported as relative ratios to a synthetic standard included as a calibration curve on each assay plate.
Time frame: 6 months
Population: 7 participants withdrew from each arm and were not included in analysis. Only participants who provided samples for this timepoint were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Third Dose BNT162b2 | Serum Level of SARS-CoV-2 Antibodies | Anti-NP | 0.0703 relative ratios | Standard Deviation 0.173 |
| Third Dose BNT162b2 | Serum Level of SARS-CoV-2 Antibodies | Anti-RBD | 0.658 relative ratios | Standard Deviation 0.438 |
| Third Dose BNT162b2 | Serum Level of SARS-CoV-2 Antibodies | Anti-Spike | 1.16 relative ratios | Standard Deviation 0.403 |
| Third Dose mRNA-1273 | Serum Level of SARS-CoV-2 Antibodies | Anti-NP | 0.0711 relative ratios | Standard Deviation 0.132 |
| Third Dose mRNA-1273 | Serum Level of SARS-CoV-2 Antibodies | Anti-RBD | 0.819 relative ratios | Standard Deviation 0.463 |
| Third Dose mRNA-1273 | Serum Level of SARS-CoV-2 Antibodies | Anti-Spike | 1.30 relative ratios | Standard Deviation 0.302 |