Transplant Trial Watch

Immunogenicity and safety of double dosage of pneumococcal vaccines in adult kidney transplant recipients and waiting list patients: A non-blinded, randomized clinical trial.

Larsen, L., et al.

Vaccine 2022; 40(28): 3884-3892


Aims
The aim of this study was to examine whether prime-boost vaccination with double dosage of 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPV23) enhances the serologic response in kidney transplant recipients (KTRs) or patients on the kidney transplant waiting list (WLPs).

Interventions
Patients were randomly assigned to receive either normal dosage vaccination (PCV13 (0.5 ml) followed by PPV23 (0.5 ml)) or double dosage vaccination (PCV13 (1.0 ml) followed by PPV23 (1.0 ml)).

Participants
76 KTRs and 66 WLPs.

Outcomes
The primary outcome was the number of participants reaching a protective response five weeks following PPV23 (at week 17). Secondary outcomes were (a) protective response at week 12 and 48; (b) number of ≥ 2-fold increases in serotype-specific antibodies at week 12, 17 and 48; and (c) increases in the 12 individual antibodies after PPV23. Safety outcomes were also assessed.

Follow-up
48 weeks

CET Conclusions
The open-label randomised controlled trial tested whether prime boost vaccination of a double-dose of 13-valent pneumococcal conjugate vaccine (PCV13; 1.0 ml) and 23-valent pneumococcal polysaccharide vaccine (PPV23; 1.0ml) showed an enhanced serologic response compared to normal dosage (ND) vaccination (PCV13 (0.5 ml) followed by PPV23 (0.5 ml)) in kidney transplant recipients (n=74) and waitlisted patients (n=65). The power analysis was based on previous data, and estimated that 39 patients in each arm would be required to detect an improvement in primary outcome of 30% with 80% power. The modified intention to treat analysis showed that the proportion of participants reaching the primary outcome “protective response” was significantly higher at 5 weeks in the DD group compared to the ND group among waitlisted patients. However, at 48 weeks, the difference was no longer significant. There were no differences between groups among the kidney transplant recipients at any time point up to 48 weeks. None of the reported serious adverse events were related to PCV13 or PPV23.

Jadad score
2

Data analysis
Modified intention-to-treat analysis

Allocation concealment
No

Trial registration
EudraCT - 2016–004123-23

Funding source
Non-industry funded