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Table 1 Study trial schedule

From: Vancomycin versus daptomycin for the treatment of methicillin-resistant Staphylococcus aureus bacteremia due to isolates with high vancomycin minimum inhibitory concentrations: study protocol for a phase IIB randomized controlled trial

Assessments

Pre-screening activity

Screening2and Randomization

While on treatment3

Follow-up period

Day of study

Pre-3rdor 4thdose of vancomycin

1-61

7 (+/-3)

8-131

14 (+/-3)

15-201

21 (+/-3)

22-271

28 (+/-3)

29-341

35 (+/-3)

36-411

42 (+/-3)

43-481

49 (+/-3)

50-551

56 (+/-3)

60 days after index culture15(-7 or + 14 days)

Informed consent

 

x

                  

Review of eligibility criteria

 

x

                  

Randomization and dosing 4

 

x

                  

Demographics

 

x

                  

Medical history 5

 

x

                  

Physical examination 6

 

x

  

x

 

x

 

x

 

x

 

x

 

x

 

x

 

x

x

Adverse event monitoring 7

   

x

x

x

x

x

x

x

x

x

x

x

x

x

x

x

x

x

Concomitant medication monitoring 8

 

x

 

x

x

x

x

x

x

x

x

x

x

x

x

x

x

x

x

x

Adherence check

   

x

x

x

x

x

x

x

x

x

x

x

x

x

x

x

x

 

Vancomycin MIC 9 testing

x

                   

FBC 10

 

x

  

x

 

x

 

x

 

x

 

x

 

x

 

x

 

x

 

Creatinine 11

 

x

  

x

 

x

 

x

 

x

 

x

 

x

 

x

 

x

 

CK 12

 

x

  

x

 

x

 

x

 

x

 

x

 

x

 

x

 

x

 

Vancomycin trough level 13

  

x

 

x

 

x

 

x

 

x

 

x

 

x

 

x

 

x

 

Daptomycin trough and peak level 14

    

x

               

Blood culture

x15

 

To be done daily until two consecutive negative sets

x

CXR 16

 

x

                  

Echocardiogram 17

   

x

                

Urine pregnancy test 18

 

x

                  

Charlson comorbidity index

 

x

                  
  1. 1These assessments to be done only for patients who remain inpatients. 2Screening blood tests: full blood count, creatinine, creatine kinase, as well as chest radiograph will be accepted if done within 48 hours prior to screening. 3Duration of therapy will be determined based on type of bacteremia. 4Randomization and first dose of study drug may take place up to one day from screening. Eligibility criteria will be reviewed again if randomization and first dose of study drug takes place one day from screening. 5Full medical history including comorbidities, current medication, allergies, and presenting and current symptoms. 6Includes vital signs for temperature, blood pressure (systolic and diastolic), heart rate, respiratory rate, and pulse oximetry. Vital sign readings will be considered to be the readings documented by the investigator during the study visit. 7Adverse event monitoring will be done weekly in patients who are receiving treatment in an outpatient setting. 8Concomitant medication monitoring will be done weekly in patients who are receiving treatment in an outpatient setting. 9Mean inhibitory concentration (MIC) test results done within 48 hours prior to screening can be used. 10Full blood count: hemoglobin, total and differential white blood cell counts, and platelet count 11Patients with prior end-stage renal failure already on longterm hemodialysis or peritoneal dialysis will not require serum creatinine monitoring. 12Creatine kinase. 13For patients randomized to the vancomycin arm only. Blood for the first trough level will be drawn immediately prior to infusion of the 3rd or 4th dose of vancomycin (inclusive of doses received prior to study enrolment) and the dose will be adjusted accordingly to achieve a trough level of 15 to 20 ug/ml. For patients whose 3rd or 4th dose of vancomycin was received prior to study enrolment, a vancomycin trough level should be taken within 48 hours of enrolment. All patients will have a trough level measured at least every seven days (+/-three days) but additional levels may be required for dose titration at the discretion of the pharmacist or the managing physician. 14For patients randomized to the daptomycin arm only. Blood for the trough level will be drawn immediately prior to the infusion of daptomycin and blood for the peak level will be drawn 30 minutes after the infusion has completed. This will only be done once on day seven (+/-three days) of the study. 15The index blood culture is the first blood culture which grows MRSA that has an MIC ≥ 1.5 ug/ml obtained in the pre-screening period. 16Chest radiograph.17Echocardiogram will be done once within the first 10 days of randomization.18Only for female patients of child-bearing potential.
  2. MIC = minimum inhibitory concentration, FBC = full blood count, CK = creatine kinase, CXR = chest radiograph.