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Quiz
Quiz
Quiz
Quiz
Quiz
100
What’s the timeframe for reassessment of potassium, eGFR or UACR at run in and screening after initial measurement?
No timeframe has been specified, this is at the Investigator’s discretion. Please bear in mind that after the screening visit, eligible subjects should be randomized within 14 days.
100
If study drug is restarted, when does the up-titration visit need to take place?
If study drug was interrupted for more than 7 days, as per protocol version 2.0, an up-titration visit should take place within 4 weeks + 7 days, to ensure eGFR and potassium levels are acceptable.
100
Is there a timeframe for potassium re-tests for eligibility purposes?
No, the timing is at Investigator´s discretion.
100
After randomization should patients be on maximum tolerated doses of ACEI or ARB?
Yes, the expectation is that patients continue on maximal tolerated labeled dose of ACEI or ARB after randomization. However, if necessary, dose adjustments are permitted following randomization.
100
Is it mandatory to calculate the Child Pugh score for eligibility purposes?
No, if a patient has no history of hepatic disease, then there is no need to calculate Child Pugh Score. Usually, the physician will be aware or have a very high suspicion that a patient has hepatic insufficiency or cirrhosis, especially for Child Pugh C as this represents advanced liver disease. The clinical features are usually apparent (e.g. abdominal ascites, previous history of variceal hemorrhages and hepatic encephalopathy.) so the expectation is that this information would be readily available in the patient records. In the infrequent occasion where an INR is required for the calculation of the Child Pugh score it may be performed locally. c.f. No specific testing is required for Addison’s in the studies. As Addison’s disease is rarely undiagnosed due to the severity of its symptoms we expect nearly all cases to already be known and therefore no additional testing is mandated.
200
If study drug is accidentally stopped by the patient does the lower dose need to be initiated on restarting?
If the study drug was interrupted for more than seven days, regardless of the reason for the interruption, the protocol stipulates to restart at the lower dose of 10mg.
200
When is the three month period for rescreening calculated from?
The three month time period commences from the initial run in visit date when the original eligibility assessments were made.
200
If an ACEI or an ARB has to be interrupted after randomization can the patient still continue in the study and receive study drug?
The interruption of RAAS agents after randomization is permitted in the protocols and no maximum period of interruption is stipulated. Subjects can stay in the study and continue study treatment but any change of concomitant medication must be registered in RAVE.
200
What is the definition of “first morning void”, concerning urine samples? a. If a patient goes to sleep at midnight and wakes at 3am, goes to the bathroom and then goes to sleep again and wakes at 8am: ?? b. If a patient goes to sleep at 10pm and wakes at 4am, goes to the bathroom and then goes to sleep again and wakes at 6am: ??
a. If a patient goes to sleep at midnight and wakes at 3am, goes to the bathroom and then goes to sleep again and wakes at 8am: consider 8am as the first morning void. b. If a patient goes to sleep at 10pm and wakes at 4am, goes to the bathroom and then goes to sleep again and wakes at 6am: consider 4am as the first morning void. (For detail refer to Medical Q&A 63)
200
If eGFR is < 25 during the study, is it mandatory to stop study medication?
No, it is not mandatory to stop treatment with study drug. However, Investigators need to carefully check potassium and eGFR values at subsequent visits, or more frequently if clinically indicated. If there is any suspected safety risk, it is at the Investigator’s clinical discretion to consider interruption or change to study drug dosing.
300
The central lab has been unable to perform HbA1c at run in, is a retest permitted? If HbA1c value is > 12% at either run in or screening visits, is a retest permitted?
If Covance is unable to provide a HbA1c value at run in due to a technical issue, a re-test may be performed. Please note, as per protocol version 2.0, as long as the patient has one valid HbA1c result from either the run in or screening visit, this is acceptable. Local HbA1c values cannot be used for eligibility but may be used as guidance, i.e. to give the Investigator a better understanding of how likely it is to have a valid HbA1c value for eligibility visits. Please note, if the HbA1c value is > 12% at either run in or screening visits, no re-test is allowed.
300
What happens if a patient is using potassium lowering agents?
Chronic use of potassium lowering agents, where the agent was used prior to enrolment may be continued. We discourage the initiation of potassium lowering agents during the run in and screening periods, as the aim is not to artificially reduce potassium levels to allow the inclusion of subjects into the study. This temporary and artificial reduction of potassium during the assessment of eligibility may lead to rebound higher rates of hyperkalemia during study treatment. During study drug treatment, there are no restrictions on the duration or frequency of potassium lowering agents as long as they are clearly documented on the concomitant medication eCRF page. The potassium binder, patiromer is acceptable (ZS-9 has currently not gained FDA approval).
300
The patient forgot to take his hypertension meds and now his readings are ineligible?
If at the screening visit, before any assessments (particularly venepuncture) the Investigator finds the patient has forgotten to take his antihypertensive medications, it is permissible to reschedule the screening visit.
300
Given the change in body weight is chosen for a safety variable, would you be able to please clarify the percentage change in body weight that is required for the change in body weight to be noted as an AE?
Specifying the exact percentage weight change for Investigators to report as an AE is difficult, as it depends on several factors such as the time course of the weight change or if it was attributed to purposeful alterations in diet or activity. It is helpful instead for Investigators to report any weight loss they deem significant plus any potential reasons why the change has occurred.
300
If an ACEI or an ARB has to be interrupted after randomization can the patient still continue in the study and receive study drug?
The interruption of RAAS agents after randomization is permitted in the protocols and no maximum period of interruption is stipulated. Subjects can stay in the study and continue study treatment but any change of concomitant medication must be registered in RAVE.
400
If a patient after an RI visit for study A is screen failed, but the patient is still eligible for Study B, when should the switch be recorded in IXRS? At the end of the RI phase or when the PIIC of study B is signed? Is it possible record the switch even if the RI phase is not completed?
It is recommended to switch the patient at the end of the Run-In or end of Screening period. Switching can be done before these periods are completed, but we recommend that the patients are kept in the Run-in or Screening period as long as possible in order to give sufficient time to really confirm eligibility and perform any retests where applicable. Subjects should only be screen failed on the day of switching. Consent for the study the patient is switching to, must be obtained prior to switching the subject in IxRS.
400
What is the longest time urine can be stored before being sent to central lab?
Based on the American Diabetes Association position statement, released in 2011 on Diabetes Care, albumin is generally stable in urine stored at 2–8 °C for 14 days. Urine samples are stable for longer periods when frozen at -80°C.
400
What should you do if local Potassium is > 5.5 or the eGFR is < 25 at visit 1?
Potassium is > 5.5: Withhold study drug. The frequency of re-tests for local potassium is at the discretion of the investigator. In case local potassium is <=5.0 on re-testing, study drug can be started. eGFR is < 25: The start of study drug and re-testing of renal function is at the discretion of the investigator based on the clinical status of the subject and the stability of the eGFR.
400
How is a history of CVD defined? (More than 5)
[CAD] Previous myocardial infarction Coronary revascularization Angiographic evidence of coronary stenosis ≥ 50% [CVA] Previous ischemic stroke [PAD] Non-traumatic leg amputation Lower-limb revascularization Intermittent claudication with ankle brachial pressure index (ABPI) of ≤ 0.80 Carotid endarterectomy or carotid stenting
400
The site accidentally used the incorrect consent form (for the other study), how should the site deal with this?
The patient should sign the correct consent form at the next available opportunity. The site should explain the error to the patient and document the discussion. The patient should annotate the incorrectly signed consent form stating that they consented to all procedures being performed for the other (incorrect study) and do not object to the use of the data collected. Both consent forms should be filed. There is no need to delete data collected under the ‘incorrect’ consent form (e.g. at Covance).
500
A patient is unable to attend their scheduled visit and pick up study drug due to a long holiday, what is the procedure? In this scenario the patient will run-out of medication before a new medication kit can be dispensed so we recommend to:1-2-3-4
1. Record the interruption of the study drug in the eCRF (RAVE) to reflect reality 2. Perform the next visit as soon as possible following the patient return (a protocol deviation will be marked by the system if out of predefined timelines, the site can explain the reason for the protocol deviation in a comment). 3. Restart study drug at the lower dose of 10mg 4. Continue study drug and uptitrate as per protocol
500
How should we report a missing bottle in RAVE? Additionally the patient claims to have thrown it away when empty and that he has taken a pill a day, which fits with the timeframe. Is it fine to enter it in RAVE even though the pill count cannot be verified?
In the event no bottle was returned, date returned and number returned should be blank and a comment should be added. Regarding the number taken, it should be the number of tablets taken, if the subject knows it and the data is plausible, then this can be documented in the source and we can use this information.
500
How does the site enter visit in IXRS for patients that are on a Study Drug interruption or if they have permanently stopped SD?
There is no need to make an IxRS transaction if no medication is being dispensed.
500
What is the difference between an Additional Medication vs Medication Replacement transaction in IXRS?
If for example a scheduled visit is postponed and more medication of the current dose the subject is on to prevent him/her from running out of medication the site should request this via the Additional Medication transaction. The Medication Replacement transaction changes the status of the previous kits to lost/damaged, which they’re not in this case. Please make sure the site staff are also aware of this distinction.
500
What should site do if overdose of study medication is reported? (RAVE, Safety reporting, assessment)
Actual dose taken should be entered in the study drug exposure page in the eCRF: It is not mandatory to report the overdose as a (S)AE if no clinical symptoms or signs were observed by the investigator. If investigator chooses to report as a (S)AE, a clear description of the event (e.g. patient accidentally took two tablets per day for x days) should be entered as the event. Appropriate safety assessments should be performed (potassium, eGFR, vital signs) per investigator’s clinical judgment.