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Table 1 The ARREST trial assessment schedule

From: Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia (ARREST): study protocol for a randomised controlled trial

 

Day

 

Screening

0

1

2

3

5

7

10

14

Weekly until discharged

84

Potential failure/recurrence

All patients

Eligibility assessment

X

           

Patient information sheet and consent

X

           

Randomisation

 

X

          

Clinical assessment(a)

 

X

  

X

 

X

X

X

X

X

X

Resource utilisation(b)

 

X

    

X

 

X

X

X

 

EQ-5D

 

X

    

X

 

X

 

X

X

Blood culture with sensitivities (10 ml)(c)

(X)

X

  

X

 

X

    

X

EDTA blood(d) (1.5 ml)

 

X

          

Clotted blood(e) (5 ml)

            

CRP

(X)

X

  

X

  

X

X

  

X

ALT, ALP, bilirubin

(X)

   

X

  

X

    

Serum storage

 

X

  

X

   

X

   

Whole blood(f) (5 ml)

 

X

          

Subset of patients recruited to the intensive PK/PD substudy (g)

Lithium heparin blood (3 × 3 ml/ time point) for antibiotic concentration assays(h)

 

X

  

X

 

X

     

Lithium heparin blood (10 ml) for compartment studies(i)

 

X

X

X

X

X

X

X

X

   

Clotted blood(e) (5 ml)

            

CRP

 

X

X

X

X

X

X

X

X

  

X

ALT, ALP, bilirubin

    

X

  

X

    

Creatinine

 

X

  

X

  

X

    

Serum storage

 

X

X

X

X

X

X

X

X

  

X

Blood culture (10 ml)

 

X

X

X

X

X

X

X

X

  

X

Subset of patients recruited to the sparse PK/PD substudy (j)

Lithium heparin blood (3 × 3 ml in total) for antibiotic concentration assays(j)

 

X

  

X

       

Clotted blood(e) (5 ml)

            

CRP

 

X

  

X

  

X

X

  

X

ALT, ALP, bilirubin

   

X

  

X

     

Creatinine

 

X

          

Serum storage

 

X

  

X

   

X

  

X

Blood culture (10 ml)

 

X

X

X

X

 

X

    

X

  1. () indicates tests that will have already been performed as part of standard management.
  2. *If a patient has already been discharged from hospital before day 7, 10 or 14, additional investigations requiring a blood draw (culture, CRP, ALT, ALP, bilirubin, serum storage) are not required (patients should not be asked to attend outpatient appointments on these days, but to return at 12 weeks only).
  3. (a) Including likely source and focus of infection, co-morbidities, duration of symptoms, temperature and record of concomitant medications (including all non-study antibiotics) at enrolment. Follow-up assessments will record new symptoms and signs indicating secondary site infections, all surgical interventions performed to treat the disease, grade 3 or 4 or serious adverse events, adverse events of any grade leading to modification of rifampicin/placebo dose or interruption/early discontinuation, any drug interactions leading to dose modification of any drug (including concomitant medications) and all changes in antimicrobial prescribing.
  4. (b) Resources used whilst in hospital will be recorded by health-care professionals (or any assigned representatives). These will include days spent in wards, procedures or laboratory tests undertaken and concomitant medication. After discharge, resource use will be self-reported by the patient. A data collection form will be developed that records post-discharge re-hospitalisations and contact with clinicians (hospital, GP, etc.).
  5. (c) Blood cultures will have already been taken prior to the screening assessment from which the potential S. aureus bacteraemia will have been identified. S. aureus isolated from blood cultures taken on days 0, 3 and 7 must have at least rifampicin susceptibility tests performed in order to evaluate the secondary endpoint acquisition of rifampicin resistance, although typically the routine panel of antimicrobial sensitivities will be performed (all susceptibilities will be recorded). All S. aureus isolates to be stored locally, then shipped annually to central storage facility in Oxford and Brighton for biobanking. All repeat isolates will be genotyped to define relapse or re-infection. Blood cultures may be taken at any other time points necessary for clinical management of the patient. If these are considered to reflect potential failure of treatment or recurrence, then sensitivities should be performed as above. Results of any additional blood cultures done should be recorded on ARREST CRFs, and S. aureus isolates stored and rifampicin susceptibility tested.
  6. (d) For measurement of haemoglobin, white cell count, lymphocytes, neutrophils, platelets.
  7. (e) For measurement of C-reactive protein (CRP), alanine transaminase (ALT), bilirubin and alkaline phosphatase (ALP) at time points shown. Serum creatinine will only be measured in the PK/PD substudies on days 0, 3, and 10; 2 ml of serum will be saved from clotted blood taken as shown, stored locally, then shipped to a central archive at King’s College London. CRP and liver function tests are routine investigations for patients with suspected S. aureus bacteraemia, and results of pre-screening investigations should also be recorded on the screening CRF.
  8. (f) 2.5 ml into EDTA and 2.5 ml into PAXgene blood RNA tube (Qiagen). Store EDTA blood for later DNA extraction and PAXgene tube for later RNA extraction. Samples will be stored locally before shipping to King’s College London for DNA/RNA extraction and archiving if the patient has consented for human DNA/RNA storage.
  9. (g) Only patients enrolled at Guy’s and St. Thomas’, University College London and Addenbrookes Hospitals will be approached.
  10. (h) A total of 9 × 3-ml blood samples will be taken for drug concentration assays. Aliquots of plasma will be rapidly frozen at -700C and stored locally before shipment in batches to Liverpool for subsequent measurement of antibiotic concentrations. Day 0 samples will be taken after the initial dose of study drug.
  11. (i) 10 ml of blood will be taken and centrifuged over fycol to separate the blood into plasma, peripheral blood mononuclear cells and neutrophil fractions. Each fraction will be cultured and cells will be frozen for later characterisation.
  12. (j) A total of 3 × 3-ml blood samples will be taken for drug concentration assays. Only patients enrolled at Oxford, Liverpool and Brighton will be approached. Day 0 samples will be taken after the initial dose of study drug.
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ISSN: 1745-6215