COVID-19 Acute Respiratory Distress SyndromePhase 4WHONCT04961229
Booster Dose of COVID-19 Vaccine for Kidney Transplant Recipients Without Adequate Humoral Response
A Phase 4 study testing The Pfizer mRNA-based BNT162b2 vaccine in people with COVID-19 Acute Respiratory Distress Syndrome and Immunosuppression, run by dafna yahav.
Trial summary
Introduction: Inadequate antibody response to mRNA SARS-CoV-2 vaccination has been described among kidney transplant recipients. Immunosuppression level and specifically, use of antimetabolite in the maintenance immunosuppressive regimen, are associated with inadequate response. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19 Acute Respiratory Distress Syndrome, Immunosuppression
- What is being tested?
- The Pfizer mRNA-based BNT162b2 vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 504 participants
- Where
- No sites listed yet
- Study dates
- Oct 2021to Jul 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- kidney transplant recipients that received two doses of BNT162b2 vaccine at least 3 weeks prior to enrollment, and were seronegative (IgG against the spike protein of SARS-CoV-2 below 50 AU/ml) at least two weeks after the second vaccine dose
- Additional inclusion criteria for the RCT:
- Recipients treated by three anti-rejection medications including: prednisone, tacrolimus, mycophenolate mofetil or mycophenolic acid.
- Tacrolimus trough blood levels 5-10 nGr/ml (lower or higher doses will have to be adjusted before re-considering for inclusion)
Who cannot join
- Past infection with SARS-CoV-2
- Pregnancy
- Age below 18 years
- Active infection
- Additional exclusion criteria for RCT only:
- Recipients at a high risk for acute or chronic humoral rejection including:
Show all 16Show fewer
- Recipients with positive panel-reactive antibody (PRA) (any positive value) at any time before or after transplantation
- Recipients that had an acute rejection in the last year
- Recipients less than 6 months after transplantation
- Recipients that are considered at high risk for rejection according to the primary care nephrologist
- Recipients taking less than 3 anti-rejection medications
- Recipients currently treated with mTOR inhibitors (everolimus, sirolimus) and/or azathioprine
- Recipients treated with plasmapheresis in the previous 3 months
- Recipients treated with eculizumab in the last year
- Recipient treated with IVIG in the previous 3 months
- Recipient treated with rituximab in the previous 6 months
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Booster Dose of mRNA SARS-CoV-2 Vaccine for Kidney Transplant Recipients Without Adequate Humoral Response With or Without Immunosuppression Reduction - Protocol for a Randomised Controlled Trial (BECAME Study)
Introduction: Inadequate antibody response to mRNA SARS-CoV-2 vaccination has been described among kidney transplant recipients. Immunosuppression level and specifically, use of antimetabolite in the maintenance immunosuppressive regimen, are associated with inadequate response. In light of the severe consequences of COVID-19 in solid organ transplant recipients, we believe it is justified to examine new vaccination strategies in these patients.
Methods and analysis: BECAME is a single center, open label, investigator-initiated randomised controlled, superiority trial, aiming to compare immunosuppression reduction combined with a third BNT162b2 vaccine dose versus third dose alone. The primary outcome will be seropositivity rate against SARS-CoV-2. A sample size of 154 patients was calculated for the seropositivity endpoint assuming 25% seropositivity in the control group and 50% in the intervention group. A sample of participant per arm will be also teste for T-cell response. We also plan to perform a prospective observational study, evaluating seropositivity among ~350 kidney transplant recipients consenting to receive a third vaccine dose, who are not eligible for the randomised controlled trial.
Ethics and dissemination: The trial is approved by local ethics committee of Rabin medical center (RMC-0192- 21). Results of this trial will be published; trial data will be available. Protocol amendments will be submitted to the local ethics committee.
Read the detailed description
All recipients more than 6 months post transplantation and at least 3 weeks following second vaccine dose will be approached and invited to a first study visit.
At first visit:
- Signed informed consent will be obtained from participants willing to participate by study investigators who usually work in the transplantation clinic.
- Anti-spike antibody response will be assessed using SARS-CoV-2 IgG II Quant (Abbott©) assay. Participants who have a documented seronegative test in the last 6 weeks will not be tested again.
Participants will be invited for an additional visit once negative serology will be reported, within 7 days of serology collection. At this second visit all participants who gave informed consent to participate in either the prospective non-randomised study or RCT will receive a single vaccine dose.
In addition, participants in the RCT will be randomised into two groups:
- Third booster dose of BNT162b2 (one standard dose) with no change in immunosuppression protocol
- Third booster dose of BNT162b2 (one standard dose) with immunosuppression reduction according to protocol (mycophenolic temporary cessation 4 days before (5 half-lives) and one week (expected antibody response) after vaccination (to allow for antibody response).
Patients who will test seronegative will be informed by the study coordinator by phone in which study arm they will be participating and receive instructions for immunosuppression reduction both during the phone call and by written instructions provided to each patient during the first visit (see Appendix). Participants in the observational study will receive a third vaccine standard dose, without any change in immunosuppression (beyond routine care)
For all groups:
- Antibodies titer against spike protein will be evaluated again 2 weeks and 3, 6, 12 months after the third vaccine dose
- T-cell response will be evaluated for a subset of patients in each group (estimated 20 patients per arm) before booster dose, at 2 weeks after booster dose, and at 3 months. For T cell response quantification peripheral blood mononuclear cell (PBMC) will be stimulated for 24 hours with spike protein and secreted interferon-gamma (IFNg) will be measured by ELISA.
- Follow-up for adverse events, rejection and SARS-CoV-2 infection will be performed at 2 weeks and at three, 6 and 12 months post third vaccination dose
- Being tested
- The Pfizer mRNA-based BNT162b2 vaccine
- Keywords
- kidney transplant recipients, COVID-19, vaccine, immunosuppression reduction, randomized controlled trial
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
The Pfizer mRNA-based BNT162b2 vaccineBiological
participants who gave informed consent to participate in either the prospective non-randomised study or RCT will receive a single vaccine dose.
In addition, participants in the RCT will be randomised into two groups:
- Third booster dose of BNT162b2 (one standard dose) with no change in immunosuppression protocol
- Third booster dose of BNT162b2 (one standard dose) with immunosuppression reduction according to protocol (mycophenolic temporary cessation 4 days before (5 half-lives) and one week (expected antibody response) after vaccination (to allow for antibody response).
| Study group | Role | What they receive |
|---|---|---|
| Third dose of BNT162b2 vaccine with Immunosuppression reduction | Experimental | Third dose of BNT162b2 vaccine with reduction of mycophenolic acid dose Receives: Biological: The Pfizer mRNA-based BNT162b2 vaccine |
| Third dose of BNT162b2 vaccine without immunosuppression reduction | Experimental | Third dose of BNT162b2 vaccine without reduction of mycophenolic acid dose Receives: Biological: The Pfizer mRNA-based BNT162b2 vaccine |
| Third dose of BNT162b2 vaccine | Experimental | Third dose of BNT162b2 vaccine with no change in immunosuppression for patients that are excluded from the randomised trial Receives: Biological: The Pfizer mRNA-based BNT162b2 vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
anti-spike protein titer above 50 AU/ml 2 weeks post vaccination
positive humoral response against SARS-CoV-2
Measured: 2 weeks post vaccination
Secondary outcomes (7)
anti-spike protein titer above 50 AU/ml 3-, 6-, and 12-months post vaccination
positive humoral response against SARS-CoV-2
Measured: 3-, 6-, and 12-months post vaccination
Log transformed titer of anti-spike protein weeks and 3, 6, and 12 months post vaccination
Log transformed titer of anti-spike protein
Measured: 2 weeks and 3, 6, and 12 months post vaccination
Adverse events to booster dose using CTCAE v4.0 criteria
Severity of adverse events will be assessed using CTCAE v4.0 criteria
Measured: 2 weeks post vaccine
Acute rejection of the allograft either documented by biopsy or clinically suspected, defined as increase in creatinine by 20% from baseline, without any other plausible explanation
either documented by biopsy or clinically suspected, defined as increase in creatinine by 20% from baseline, without any other plausible explanation
Measured: 2 weeks, 3,6, and 12 months post vaccination
positive PCR test to SARS-CoV-2 during the follow up period
positive PCR test to SARS-CoV-2 during the follow up period
Measured: until 12 months following vaccine
Positive PCR tests to VZV, CMV
Other viral reactivation during the follow up period: VZV, CMV, tested according to clinical suspicion
Measured: during the follow up period
Number of hospitalizations (numerical count)
Number of hospitalizations
Measured: until 12 months following vaccine
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2021
- Study startOct 2021 (estimated)
- Primary completionFeb 2022 (estimated)
- Study completionJul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVID-19 Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 504 participants (estimated)
Sponsor and investigators
- Lead sponsor
- dafna yahav
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, dafna yahav, Rabin Medical Center
- Investigators
- Ruth Rahaminov, Principal investigator, Rabin Medical Center, Beilinson Campus, Petah-Tikva, Israel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04961229
- Sponsor's protocol ID
- 0192-21-RMC
- Acronym
- WHO
- Status last verified
- Oct 2021
- First submitted
- 13 Jul 2021
- Last updated
- 8 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: According to request
Publications
Yahav D, Rozen-Zvi B, Mashraki T, Atamna A, Ben-Zvi H, Bar-Haim E, Rahamimov R. Immunosuppression reduction when administering a booster dose of the BNT162b2 mRNA SARS-CoV-2 vaccine in kidney transplant recipients without adequate humoral response following two vaccine doses: protocol for a randomised controlled trial (BECAME study). BMJ Open. 2021 Oct 11;11(10):e055611. doi: 10.1136/bmjopen-2021-055611.
PubMed 34635537
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Booster Dose of mRNA SARS-CoV-2 Vaccine for Kidney Transplant Recipients Without Adequate Humoral Response With or Without Immunosuppression Reduction - Protocol for a Randomised Controlled Trial (BECAME Study)
- ClinicalTrials.gov ID
- NCT04961229
- Acronym / sponsor ID
- WHO / 0192-21-RMC
- Keywords
- kidney transplant recipients, COVID-19, vaccine, immunosuppression reduction, randomized controlled trial
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 504 participants (estimated)
- Lead sponsor
- dafna yahavUniversity, hospital or other
- Study start
- Oct 2021 (estimated)
- Primary completion
- Feb 2022 (estimated)
- Study completion
- Jul 2022 (estimated)
- First posted
- 14 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Introduction: Inadequate antibody response to mRNA SARS-CoV-2 vaccination has been described among kidney transplant recipients. Immunosuppression level and specifically, use of antimetabolite in the maintenance immunosuppressive regimen, are associated with inadequate response. In light of the severe consequences of COVID-19 in solid organ transplant recipients, we believe it is justified to examine new vaccination strategies in these patients.
Methods and analysis: BECAME is a single center, open label, investigator-initiated randomised controlled, superiority trial, aiming to compare immunosuppression reduction combined with a third BNT162b2 vaccine dose versus third dose alone. The primary outcome will be seropositivity rate against SARS-CoV-2. A sample size of 154 patients was calculated for the seropositivity endpoint assuming 25% seropositivity in the control group and 50% in the intervention group. A sample of participant per arm will be also teste for T-cell response. We also plan to perform a prospective observational study, evaluating seropositivity among ~350 kidney transplant recipients consenting to receive a third vaccine dose, who are not eligible for the randomised controlled trial.
Ethics and dissemination: The trial is approved by local ethics committee of Rabin medical center (RMC-0192- 21). Results of this trial will be published; trial data will be available. Protocol amendments will be submitted to the local ethics committee.
Detailed description
All recipients more than 6 months post transplantation and at least 3 weeks following second vaccine dose will be approached and invited to a first study visit.
At first visit:
- Signed informed consent will be obtained from participants willing to participate by study investigators who usually work in the transplantation clinic.
- Anti-spike antibody response will be assessed using SARS-CoV-2 IgG II Quant (Abbott©) assay. Participants who have a documented seronegative test in the last 6 weeks will not be tested again.
Participants will be invited for an additional visit once negative serology will be reported, within 7 days of serology collection. At this second visit all participants who gave informed consent to participate in either the prospective non-randomised study or RCT will receive a single vaccine dose.
In addition, participants in the RCT will be randomised into two groups:
- Third booster dose of BNT162b2 (one standard dose) with no change in immunosuppression protocol
- Third booster dose of BNT162b2 (one standard dose) with immunosuppression reduction according to protocol (mycophenolic temporary cessation 4 days before (5 half-lives) and one week (expected antibody response) after vaccination (to allow for antibody response).
Patients who will test seronegative will be informed by the study coordinator by phone in which study arm they will be participating and receive instructions for immunosuppression reduction both during the phone call and by written instructions provided to each patient during the first visit (see Appendix). Participants in the observational study will receive a third vaccine standard dose, without any change in immunosuppression (beyond routine care)
For all groups:
- Antibodies titer against spike protein will be evaluated again 2 weeks and 3, 6, 12 months after the third vaccine dose
- T-cell response will be evaluated for a subset of patients in each group (estimated 20 patients per arm) before booster dose, at 2 weeks after booster dose, and at 3 months. For T cell response quantification peripheral blood mononuclear cell (PBMC) will be stimulated for 24 hours with spike protein and secreted interferon-gamma (IFNg) will be measured by ELISA.
- Follow-up for adverse events, rejection and SARS-CoV-2 infection will be performed at 2 weeks and at three, 6 and 12 months post third vaccination dose
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Third dose of BNT162b2 vaccine with Immunosuppression reduction | Experimental | Biological: The Pfizer mRNA-based BNT162b2 vaccineThird dose of BNT162b2 vaccine with reduction of mycophenolic acid dose |
| Third dose of BNT162b2 vaccine without immunosuppression reduction | Experimental | Biological: The Pfizer mRNA-based BNT162b2 vaccineThird dose of BNT162b2 vaccine without reduction of mycophenolic acid dose |
| Third dose of BNT162b2 vaccine | Experimental | Biological: The Pfizer mRNA-based BNT162b2 vaccineThird dose of BNT162b2 vaccine with no change in immunosuppression for patients that are excluded from the randomised trial |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- kidney transplant recipients that received two doses of BNT162b2 vaccine at least 3 weeks prior to enrollment, and were seronegative (IgG against the spike protein of SARS-CoV-2 below 50 AU/ml) at least two weeks after the second vaccine dose
- Recipients treated by three anti-rejection medications including: prednisone, tacrolimus, mycophenolate mofetil or mycophenolic acid.
- Tacrolimus trough blood levels 5-10 nGr/ml (lower or higher doses will have to be adjusted before re-considering for inclusion)
Key exclusion criteria (16 listed)
- Past infection with SARS-CoV-2
- Pregnancy
- Age below 18 years
- Active infection
- Recipients at a high risk for acute or chronic humoral rejection including:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| The Pfizer mRNA-based BNT162b2 vaccineparticipants who gave informed consent to participate in either the prospective non-randomised study or RCT will receive a single vaccine dose. In addition, participants in the RCT will be randomised into two groups: 1. Third booster dose of BNT162b2 (one standard dose) with no change in immunosuppression protocol 2. Third booster dose of BNT162b2 (one standard dose) with immunosuppression reduction according to protocol (mycophenolic temporary cessation 4 days before (5 half-lives) and one week (expected antibody response) after vaccination (to allow for antibody response). | Biological | Third dose of BNT162b2 vaccine, Third dose of BNT162b2 vaccine with Immunosuppression reduction, Third dose of BNT162b2 vaccine without immunosuppression reduction |
Primary outcome
anti-spike protein titer above 50 AU/ml 2 weeks post vaccination
Time frame: 2 weeks post vaccination
positive humoral response against SARS-CoV-2
7 secondary outcomes
anti-spike protein titer above 50 AU/ml 3-, 6-, and 12-months post vaccination
Time frame: 3-, 6-, and 12-months post vaccination
Log transformed titer of anti-spike protein weeks and 3, 6, and 12 months post vaccination
Time frame: 2 weeks and 3, 6, and 12 months post vaccination
Adverse events to booster dose using CTCAE v4.0 criteria
Time frame: 2 weeks post vaccine
Acute rejection of the allograft either documented by biopsy or clinically suspected, defined as increase in creatinine by 20% from baseline, without any other plausible explanation
Time frame: 2 weeks, 3,6, and 12 months post vaccination
positive PCR test to SARS-CoV-2 during the follow up period
Time frame: until 12 months following vaccine
Positive PCR tests to VZV, CMV
Time frame: during the follow up period
Number of hospitalizations (numerical count)
Time frame: until 12 months following vaccine
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2021.
- Derived from this study: PubMed 34635537Yahav D, Rozen-Zvi B, Mashraki T, Atamna A, Ben-Zvi H, Bar-Haim E, Rahamimov R. Immunosuppression reduction when administering a booster dose of the BNT162b2 mRNA SARS-CoV-2 vaccine in kidney transplant recipients without adequate humoral response following two vaccine doses: protocol for a randomised controlled trial (BECAME study). BMJ Open. 2021 Oct 11;11(10):e055611. doi: 10.1136/bmjopen-2021-055611.
- Individual participant dataSharing planned: Yes. According to request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ruth Rahaminov principal investigator
Rabin Medical Center, Beilinson Campus, Petah-Tikva, Israel
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing The Pfizer mRNA-based BNT162b2 vaccine in people with COVID-19 Acute Respiratory Distress Syndrome and Immunosuppression, run by dafna yahav.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ruth Rahaminov (97239376475, rutir@clalit.org.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
anti-spike protein titer above 50 AU/ml 2 weeks post vaccination (time frame: 2 weeks post vaccination). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04961229, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2021.