Administrative information
Title {1} | Evaluation of the efficacy and safety of icatibant and C1 esterase/kallikrein inhibitor in hospitalized patients with pneumonia caused by Covid-19 virus infection: a study protocol for a phase II, open-label, three-armed, randomized, single-center, active control superiority trial. |
Trial registration {2a and 2b} | Brazilian Clinical Trials Registry (ReBec): RBR-5s2mqg Universal Trial Number (UTN): U1111-1250-1843 |
Protocol version [1] | Version 2.0 Nov. 18, 2020 |
Funding {4} | Funded by: Emergency project - Rapid Implementation Supplements Against COVID-19 of the Sao Paulo Research Foundation (FAPESP 2020/04522-5). Research, Inovation and Dissemination Center – Obesity and Comorbidities Research Center of the Sao Paulo Research Foundation (FAPESP 2013/07607-8). |
Author details {5a} | Obesity and Comorbidities Research Center, University of Campinas, Campinas, São Paulo, Brazil. Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil. Department of Surgery, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil. Department of Radiology, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil. Clinical Hospital, University of Campinas, Campinas, São Paulo, Brazil. School of Nursing, University of Campinas, Campinas, São Paulo, Brazil. |
Name and contact information for the trial sponsor {5b} | Clinics Hospital, University of Campinas, Campinas, São Paulo, Brazil, R. Vital Brasil, 251 - Cidade Universitária, Campinas - SP, 13083-888 |
Role of sponsor {5c} | The study sponsor and funders have no role in study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication. |
Introduction
Background and rationale {6a}
Objectives {7}
Trial design {8}
Methods: participants, interventions, and outcomes
Study setting {9}
Eligibility criteria {10}
Who will take informed consent? {26a}
Additional consent provisions for collection and use of participant data and biological specimens {26b}
Interventions
Explanation for the choice of comparators {6b}
Intervention description {11a}
Group A (experimental) plus standard care
Group B (experimental) plus standard care
Group C (active control)
Criteria for discontinuing or modifying allocated interventions {11b}
Strategies to improve adherence to interventions {11c}
Relevant concomitant care permitted or prohibited during the trial {11d}
Provisions for post-trial care {30}
Outcomes {12}
Primary outcome
Secondary outcomes
Participant timeline {13}
Enrollment | Allocation | Post-allocation | Discharge | Close-out | ||||
---|---|---|---|---|---|---|---|---|
Time point | − 1 | 0 | D1–D4 | D5–D7 | D8–D14 | D15–D28 | ||
Enrollment | ||||||||
Screening | x | |||||||
Eligibility criteria | x | |||||||
Informed consent | x | |||||||
Allocation | x | |||||||
Randomization | x | |||||||
Baseline data collection | x | |||||||
Interventions | ||||||||
Icatibant/std care | x | |||||||
C1 inhib./std care | x | |||||||
Std care | x | x | x | x | x | x | x | |
Outcome/safety assessments | ||||||||
CT of the chest | x | X (D14) | X (D28) | X | ||||
Primary outcome | x | x | x | x | x | |||
Clinical symptoms | x | x | x | x | x | x | ||
Vital signs | x | x | x | x | x | x | x | x |
ECG | x | |||||||
Adverse events | x | x | x | x | x | x | x | x |
Time mechanical ventilation | x | |||||||
Death | x | |||||||
Length of stay | x | |||||||
Laboratory tests* | Only every 4 days or at the discretion of the assistant physician | |||||||
RT-PCR SARS-CoV-2 | x | |||||||
Bradykinin | x | x | x | |||||
SOFA score | x | x | x | x | x | x | ||
Blood routine | x | x | x | x | x | x | ||
Coagulation routine | x | x | x | x | x | x | ||
CRP | x | x | x | x | x | x | ||
Liver function | x | x | x | x | x | x | ||
Kidney function | x | x | x | x | x | x | ||
d-dimer | x | x | x | x | x | x | ||
High-sensitivity troponin | x | x | x | x | x | x | ||
Pro-BNP | x | x | x | x | x | x | ||
Aspergillus antigen | x | x | x | x | x |
Sample size {14}
Recruitment {15}
Assignment of interventions: allocation
Sequence generation {16a}
Concealment mechanism {16b}
Implementation {16c}
Assignment of interventions: blinding
Who will be blinded {17a}
Procedure for unblinding if needed {17b}
Data collection and management
Plans for assessment and collection of outcomes {18a}
Plans to promote participant retention and complete follow-up {18b}
Data management {19}
Confidentiality {27}
Plans for collection, laboratory evaluation, and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}
Statistical methods
Statistical methods for primary and secondary outcomes {20a}
Interim analyses {21b}
Methods for additional analyses (e.g., subgroup analyses) {21b}
Methods of analysis to handle protocol non-adherence and any statistical methods to handle missing data {21c}
Plans to give access to the full protocol, participant-level data, and statistical code {31c}
Oversight and monitoring
Composition of the coordinating center and trial steering committee {5d}
Coordinating center
Trial steering committee
-
Maria Luiza Moretti, Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
-
Lício Augusto Velloso, Obesity and Comorbidities Research Center, Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
-
José Carlos de Lima-Júnior, Obesity and Comorbidities Research Center, Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
-
Flávia Fagundes Bueno, Obesity and Comorbidities Research Center, Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
-
Tatiana Benaglia, Department of Statistics, Institute of Mathematics, Statistics, and Scientific Computation, University of Campinas, Campinas, São Paulo, Brazil
Trial operation committee
-
Elie Mansour, Department of Internal Medicine, University of Campinas, Campinas, São Paulo, Brazil
-
Antonio L. E. Falcao, Department of Surgery, University of Campinas, Campinas, São Paulo, Brazil
-
Thiago Martins Santos, Department of Internal Medicine, University of Campinas, Campinas, São Paulo, Brazil
Data management team
-
Clarity Health Intelligence Co., Ltd.
-
Milena Monfort-Pires, Obesity and Comorbidities Research Center, University of Campinas, Campinas, São Paulo, Brazil
-
Bruna Bombassaro, Obesity and Comorbidities Research Center, University of Campinas, Campinas, São Paulo, Brazil
-
Eliana Pereira de Araújo, School of Nursing, University of Campinas, Campinas, São Paulo, Brazil