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A trial platform to assess approved SARS-CoV-2 vaccines in immunocompromised patients: first sub-protocol for a pilot trial comparing the mRNA vaccines Comirnaty® and COVID-19 mRNA Vaccine Moderna®.
Trials. 2021 Oct 21; 22(1):724.T

Abstract

BACKGROUND

Late 2019, a new highly contagious coronavirus SARS-CoV-2 has emerged in Wuhan, China, causing within 2 months a pandemic with the highest disease burden in elderly and people with pre-existing medical conditions. The pandemic has highlighted that new and more flexible clinical trial approaches, such as trial platforms, are needed to assess the efficacy and safety of interventions in a timely manner. The two existing Swiss cohorts of immunocompromised patients (i.e., Swiss HIV Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS)) are an ideal foundation to set-up a trial platform in Switzerland leveraging routinely collected data. Within a newly founded trial platform, we plan to assess the efficacy of the first two mRNA SARS-CoV-2 vaccines that reached market authorization in Switzerland in the frame of a pilot randomized controlled trial (RCT) while at the same time assessing the functionality of the trial platform.

METHODS

We will conduct a multicenter randomized controlled, open-label, 2-arm sub-study pilot trial of a platform trial nested into two Swiss cohorts. Patients included in the SHCS or the STCS will be eligible for randomization to either receiving the mRNA vaccine Comirnaty® (Pfizer/BioNTech) or the COVID-19 mRNA Vaccine Moderna®. The primary clinical outcome will be change in pan-lg antibody response (pan-Ig anti-S1-RBD; baseline vs. 3 months after first vaccination; binary outcome, considering ≥ 0.8 units/ml as a positive antibody response). The pilot study will also enable us to assess endpoints related to trial conduct feasibility (i.e., duration of RCT set-up; time of patient recruitment; patient consent rate; proportion of missing data). Assuming vaccine reactivity of 90% in both vaccine groups, we power our trial, using a non-inferiority margin such that a 95% two-sided confidence interval excludes a difference in favor of the reference group of more than 10%. A sample size of 380 (190 in each treatment arm) is required for a statistical power of 90% and a type I error of 0.025. The study is funded by the Swiss National Science Foundation (National Research Program NRP 78, "COVID-19").

DISCUSSION

This study will provide crucial information about the efficacy and safety of the mRNA SARS-CoV-2 vaccines in HIV patients and organ transplant recipients. Furthermore, this project has the potential to pave the way for further platform trials in Switzerland.

TRIAL REGISTRATION

ClinicalTrials.gov NCT04805125 . Registered on March 18, 2021.

Authors+Show Affiliations

Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, University of Basel, Basel, Switzerland. benjamin.speich@usb.ch. Nuffield Department of Orthopaedics, Centre for Statistics in Medicine, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK. benjamin.speich@usb.ch.Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, University of Basel, Basel, Switzerland.University of Zurich, Institute of Medical Virology, Zurich, Switzerland.Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Basel, University of Basel, Basel, Switzerland.Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, 3010, Bern, Switzerland.Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.Division of Pulmonology, University Hospital Zurich, Zurich, Switzerland.Nephrology Clinic, University Hospital Zurich, Zurich, Switzerland.Clinic of Respiratory Medicine and Pulmonary Cell Research, University Hospital of Basel, Petersgraben 4, 4031, Basel, Switzerland.Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, 3010, Bern, Switzerland.University of Zurich, Institute of Medical Virology, Zurich, Switzerland. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.University of Zurich, Institute of Medical Virology, Zurich, Switzerland.Clinical Virology, Laboratory Medicine, University Hospital Basel, Basel, Switzerland. Transplantation & Clinical Virology, Department Biomedicine, University Hospital Basel, Basel, Switzerland.Infectious Diseases Service, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. Transplantation Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.Infectious Diseases Service, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, University of Basel, Basel, Switzerland. Meta-Research Innovation Center Berlin (METRICS-B), Berlin Institute of Health, Berlin, Germany. Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, CA, USA.Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, University of Basel, Basel, Switzerland. Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.University of Zurich, Institute of Medical Virology, Zurich, Switzerland. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, University of Basel, Basel, Switzerland.Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, University of Basel, Basel, Switzerland.University of Zurich, Institute of Medical Virology, Zurich, Switzerland. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.No affiliation info available

Pub Type(s)

Clinical Trial Protocol
Journal Article

Language

eng

PubMed ID

34674742

Citation

Speich, Benjamin, et al. "A Trial Platform to Assess Approved SARS-CoV-2 Vaccines in Immunocompromised Patients: First Sub-protocol for a Pilot Trial Comparing the mRNA Vaccines Comirnaty® and COVID-19 mRNA Vaccine Moderna®." Trials, vol. 22, no. 1, 2021, p. 724.
Speich B, Chammartin F, Smith D, et al. A trial platform to assess approved SARS-CoV-2 vaccines in immunocompromised patients: first sub-protocol for a pilot trial comparing the mRNA vaccines Comirnaty® and COVID-19 mRNA Vaccine Moderna®. Trials. 2021;22(1):724.
Speich, B., Chammartin, F., Smith, D., Stoeckle, M. P., Amico, P., Eichenberger, A. L., Hasse, B., Schuurmans, M. M., Müller, T., Tamm, M., Dickenmann, M., Abela, I. A., Trkola, A., Hirsch, H. H., Manuel, O., Cavassini, M., Hemkens, L. G., Briel, M., Mueller, N. J., ... Kusejko, K. (2021). A trial platform to assess approved SARS-CoV-2 vaccines in immunocompromised patients: first sub-protocol for a pilot trial comparing the mRNA vaccines Comirnaty® and COVID-19 mRNA Vaccine Moderna®. Trials, 22(1), 724. https://doi.org/10.1186/s13063-021-05664-0
Speich B, et al. A Trial Platform to Assess Approved SARS-CoV-2 Vaccines in Immunocompromised Patients: First Sub-protocol for a Pilot Trial Comparing the mRNA Vaccines Comirnaty® and COVID-19 mRNA Vaccine Moderna®. Trials. 2021 Oct 21;22(1):724. PubMed PMID: 34674742.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A trial platform to assess approved SARS-CoV-2 vaccines in immunocompromised patients: first sub-protocol for a pilot trial comparing the mRNA vaccines Comirnaty® and COVID-19 mRNA Vaccine Moderna®. AU - Speich,Benjamin, AU - Chammartin,Frédérique, AU - Smith,Daniel, AU - Stoeckle,Marcel P, AU - Amico,Patrizia, AU - Eichenberger,Anna L, AU - Hasse,Barbara, AU - Schuurmans,Macé M, AU - Müller,Thomas, AU - Tamm,Michael, AU - Dickenmann,Michael, AU - Abela,Irene A, AU - Trkola,Alexandra, AU - Hirsch,Hans H, AU - Manuel,Oriol, AU - Cavassini,Matthias, AU - Hemkens,Lars G, AU - Briel,Matthias, AU - Mueller,Nicolas J, AU - Rauch,Andri, AU - Günthard,Huldrych F, AU - Koller,Michael T, AU - Bucher,Heiner C, AU - Kusejko,Katharina, AU - ,, Y1 - 2021/10/21/ PY - 2021/05/19/received PY - 2021/09/15/accepted PY - 2021/10/22/entrez PY - 2021/10/23/pubmed PY - 2021/10/26/medline KW - Organ transplant KW - Platform trial KW - Protocol KW - Randomized controlled trial, HIV KW - SARS-CoV-2 KW - Vaccine SP - 724 EP - 724 JF - Trials JO - Trials VL - 22 IS - 1 N2 - BACKGROUND: Late 2019, a new highly contagious coronavirus SARS-CoV-2 has emerged in Wuhan, China, causing within 2 months a pandemic with the highest disease burden in elderly and people with pre-existing medical conditions. The pandemic has highlighted that new and more flexible clinical trial approaches, such as trial platforms, are needed to assess the efficacy and safety of interventions in a timely manner. The two existing Swiss cohorts of immunocompromised patients (i.e., Swiss HIV Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS)) are an ideal foundation to set-up a trial platform in Switzerland leveraging routinely collected data. Within a newly founded trial platform, we plan to assess the efficacy of the first two mRNA SARS-CoV-2 vaccines that reached market authorization in Switzerland in the frame of a pilot randomized controlled trial (RCT) while at the same time assessing the functionality of the trial platform. METHODS: We will conduct a multicenter randomized controlled, open-label, 2-arm sub-study pilot trial of a platform trial nested into two Swiss cohorts. Patients included in the SHCS or the STCS will be eligible for randomization to either receiving the mRNA vaccine Comirnaty® (Pfizer/BioNTech) or the COVID-19 mRNA Vaccine Moderna®. The primary clinical outcome will be change in pan-lg antibody response (pan-Ig anti-S1-RBD; baseline vs. 3 months after first vaccination; binary outcome, considering ≥ 0.8 units/ml as a positive antibody response). The pilot study will also enable us to assess endpoints related to trial conduct feasibility (i.e., duration of RCT set-up; time of patient recruitment; patient consent rate; proportion of missing data). Assuming vaccine reactivity of 90% in both vaccine groups, we power our trial, using a non-inferiority margin such that a 95% two-sided confidence interval excludes a difference in favor of the reference group of more than 10%. A sample size of 380 (190 in each treatment arm) is required for a statistical power of 90% and a type I error of 0.025. The study is funded by the Swiss National Science Foundation (National Research Program NRP 78, "COVID-19"). DISCUSSION: This study will provide crucial information about the efficacy and safety of the mRNA SARS-CoV-2 vaccines in HIV patients and organ transplant recipients. Furthermore, this project has the potential to pave the way for further platform trials in Switzerland. TRIAL REGISTRATION: ClinicalTrials.gov NCT04805125 . Registered on March 18, 2021. SN - 1745-6215 UR - https://www.unboundmedicine.com/medline/citation/34674742/A_trial_platform_to_assess_approved_SARS_CoV_2_vaccines_in_immunocompromised_patients:_first_sub_protocol_for_a_pilot_trial_comparing_the_mRNA_vaccines_Comirnaty®_and_COVID_19_mRNA_Vaccine_Moderna®_ L2 - https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-021-05664-0 DB - PRIME DP - Unbound Medicine ER -