We are pleased to share that REPRIEVE is closing to follow up based on the observed efficacy of the study treatment to reduce major adverse cardiovascular events following a planned interim review of the data. Please check back here for FAQs regarding study closure.
Statin Use After REPRIEVE: Guidance for Site Investigators and Participants
Click here to view guidance for providers.
Click here to view guidance for participants.
Study Termination Visits
1When can I begin to bring participants in for their study termination visit? Should we do the study termination visit at the next scheduled visit? Even if we are waiting for IRB approval of the participant letter?
Study termination visits may begin at the discretion of each site immediately. The current version of the protocol includes provisions for final study visits. No additional IRB approval is required for this to happen. The participant letter should be submitted to your IRB and sites should follow local guidance on informing participants of the content of this letter.
2Many of the study closure dates are based on the "last participant visit at my site." Is there a resource to help us determine when these dates will be?
We know that many activities on the Study Closure SOP are based on the last study termination visit at each individual site. To help you determine the dates based on the last study termination visit at your site, we developed a Study Closure Date Calculator. Please click here to download the calculator.
3We have a participant who is still on study, but cannot physically come to our site for the study termination visit, how do we proceed?
We ask that sites do their best to encourage participants to return for their final visits. If participants are unable or unwilling to return, then please collect as much information as possible remotely. Please see below for options for conducting the study termination visit:
1. Complete all CRFs by doing the Study Termination visit with the subject in person at the clinic (preferred)
OR
2. Do a phone visit and/or EMR review and complete as many of the Study Termination visit crfs as possible with
the data from those sources; enter any CRFs you couldn't get data for as 'Evaluation not performed'
OR
3. If both a phone visit with the subject and EMR review are not possible, mark the Study Termination 'Stopped'/ missed
in OpenClinica. The statisticians have instructed us to have sites to do that rather than making sites enter ALL the CRFs
at the Study Termination visit as 'Eval not performed'.
4What happens if a participant misses their study termination visit and are unable to return for an in-person visit?
While we would like the study termination visit to be in person, if the participant misses the in-person visit, then data can be collected remotely (i.e. phone call or chart review) as per section 4.3 of the MOPS.
If you are unable to contact a participant to schedule their study termination visit, despite multiple efforts, this should be treated as a missed visit however, the Medications log (TXW0295), the Off Study CRF (RP0001) and the Permanent Discontinuation of Study Medication (RP0003) must be completed.
Please see below for options for conducting the study termination visit:
1. Complete all CRFs by doing the Study Termination visit with the subject in person at the clinic (preferred)
OR
2. Do a phone visit and/or EMR review and complete as many of the Study Termination visit crfs as possible with
the data from those sources; enter any CRFs you couldn't get data for as 'Evaluation not performed'
OR
3. If both a phone visit with the subject and EMR review are not possible, mark the Study Termination 'Stopped'/ missed
in OpenClinica. The statisticians have instructed us to have sites to do that rather than making sites enter ALL the CRFs
at the Study Termination visit as 'Eval not performed'.
5Because we are taking participants off-study during the study termination visit, will we all need to complete the VSW0025 - Vital Status and Endpoint Follow-up form?
The VSW0025 CRF is to be completed annually beginning one year after the Date of Off-Study for participants who prematurely discontinued REPRIEVE before the study closure announcement and did not withdraw consent. If you have participants who meet these criteria who you have not completed the VSW0025 - Vital Status and Endpoint Follow-up form for yet, please do so by the deadline of July 31, 2023. Even if contact is not obtained, record the attempt and date of attempt in Section A of the log.
On the other hand, all participants who were still on study at the time of the REPRIEVE closure announcement, including potential lost-to-follow-up participants, will be considered to have fully completed REPRIEVE when your site enters the Study Termination visit for them in OpenClinica. DO NOT complete the VSW0025 CRF for these fully-completed participants, including if your site learns one of these participants experienced an endpoint event after the Study Termination visit.
On the other hand, all participants who were still on study at the time of the REPRIEVE closure announcement, including potential lost-to-follow-up participants, will be considered to have fully completed REPRIEVE when your site enters the Study Termination visit for them in OpenClinica. DO NOT complete the VSW0025 CRF for these fully-completed participants, including if your site learns one of these participants experienced an endpoint event after the Study Termination visit.
Participants Lost to Follow Up
1What if the participant is lost to follow up (meaning still on study at time of closure announcement but no recent contact), and we can't reach them at all prior to the study termination visit deadline of July 31 for all participants? Do we document them as loss to follow up?
If you are unable to contact a participant to schedule their study termination visit, despite multiple efforts, this would be treated as a missed visit however, the Medications log (TXW0295), the Off Study CRF (RP0001) and the Permanent Discontinuation of Study Medication (RP0003) must be completed.
2We have some participants who are lost to follow up, do we complete the Premature Study Discontinuation Visit CRFs or the Study Termination CRFs for this participant?
For participants who have not prematurely discontinued the study, prior to the notice of study closure, all visits should be study termination visits between the date of study closure announcement and the deadline for completion of study termination visit for all participants currently on study (July 31, 2023).
3My site team was on the verge of declaring one of our participants lost to follow up due to no contact. Do I complete the forms at the Study Termination visit for that participant rather than the Premature Study Discontinuation visit forms?
Yes, for participants who have not prematurely discontinued the study, all visits should be study termination visits between the time of study closure announcement and the deadline for completion of study termination visit for all participants currently on study (July 31, 2023).
Lab and Clinical Data Collection
1If participants come in for their study termination visit and are non-fasting, should we draw the storage samples at that visit anyway if they are not able to return? (I am concerned that some people just won’t come back for their fasting blood draw).
It is preferable that participants are fasting for the final blood collection, however if they are not fasting and you suspect that they would not return for a fasting blood draw please proceed with the blood collection.
If a participant does a non-fasting blood draw at the Study Termination visit for any reason, contact reprieve.dmc@fstrf.org with the corresponding PID and the data managers will switch the SPW form version for the Study Termination visit. This is so that it can be reported that the participant was not fasting for the blood draw.
2In the LDMS preload we are supposed to enter month on study. Do we calculate the total number of months the participant has been on study using 30 days = 1 month? We have a study termination visit and the participant is slightly out of window for month 76 (he would be month 77). So we would put 77 EOS into the LDMS preload?
According to the LPC, the study termination visit should be the actual study month # with EOS for the visit unit, so you are correct in suggesting to enter 77 EOS in the LDMS preload.
3The Schedule of Evaluations in the A5332 protocol indicates that at discontinuation visits, CD4+/CD8+, HIV-1 RNA, CBC, and creatinine from clinical care within 180 days of the visit will be used. If a participant does not have a result available within 180 days what do I do?
If results are unavailable from clinical care within 180 days of the visit but you anticipate that the participant will have any of these labs drawn close to the 3-week data entry deadline after the visit, please do not complete the RP0001 until after the results from clinical care have been entered in OpenClinica. Otherwise, if results will not be available indicate this on the LBW CRFs in OpenClinica.
4As far as receipt of vaccines prior to the study termination visit blood draw, is it preferred not to draw samples if they have received a vaccine within 7 days (or 14 for COVID vaccine) of the final visit, but we should obtain the samples if we think it’s unlikely we can get the participant back in?
Yes, we prefer that participants not receive vaccines within 7 days (or 14 days if COVID vaccine) of the study termination. See A5332 MOPS Section 13.0, but use your judgement if you think the participant won't return, then complete the visit and obtain the fasting blood.
Vital Status and Endpoint Assessment
1I have a participant who has prematurely discontinued REPRIEVE but did not withdraw consent. Therefore we have been completing the Vital Status and Endpoint Assessment CRF (VSW0025) with this participant annually. The participant reported having an admission for chest pain last month. What do I do now?
Instructions are in the A5332 MOPS, section 12.6 Vital Status and Endpoint Assessment. On the VSW0025, if a potential MACE or death is identified, complete Section B:
- Key event into this form only
- Do NOT key the event into the AE Log or the TRK0150
- Once the event is keyed into Section B of the Vital Status and Endpoint Follow-up form, complete the corresponding Adjudicated Event form and follow instructions in section 6.1.3 of the MOPS.
- Key event into this form only
- Do NOT key the event into the AE Log or the TRK0150
- Once the event is keyed into Section B of the Vital Status and Endpoint Follow-up form, complete the corresponding Adjudicated Event form and follow instructions in section 6.1.3 of the MOPS.
2If we recently completed a Vital Status and Endpoint Assessment Follow Up for a participant who prematurely discontinued the trial prior to the study closure announcement would we complete the VSW0025 again if we contact them to inform them of study closure?
No, you would not need to complete the VSW0025 again if it was completed recently. The CRF needs to be completed annually based on the date of off study, so if it becomes overdue before the study termination visit deadline of July 31, 2023 then it will need to be completed before this time.
3I have a participant which we are collecting Vital Status only. He had an admission for chest pain last month. I’ve completed the Adjudicated Event Form in Openclinica. Do I need to send the redacted hospital records for this event? The Vital Status and Endpoint Follow-up form does not indicate that should be done.
Please see the corresponding instructions from section 12.6 'Vital Status and Endpoint Assessments' of the REPRIEVE MOPs below. In summary, yes, please complete the corresponding Adjudicated Event form for this event in the 'Adjudicated Event Forms' column of OpenClinica and submit a source document packet for the event to the REPRIEVE MGH group.
If a potential MACE event or death is identified, complete Section B on the Vital Status and Endpoint Follow-up CRF. Key the event into this form only. Indicate the type of MACE or death event that occurred. Do not key the event into the AE Log or the Adjudicated Events Tracking CRF (TRK0150). Once the event is keyed into Section B of the Vital Status and Endpoint Follow-up form, complete the corresponding Adjudicated Event form and follow instructions in section 6.1.3 of the MOPS.
If a potential MACE event or death is identified, complete Section B on the Vital Status and Endpoint Follow-up CRF. Key the event into this form only. Indicate the type of MACE or death event that occurred. Do not key the event into the AE Log or the Adjudicated Events Tracking CRF (TRK0150). Once the event is keyed into Section B of the Vital Status and Endpoint Follow-up form, complete the corresponding Adjudicated Event form and follow instructions in section 6.1.3 of the MOPS.
Study Product
1Can participants be unblinded before November 2023?
We understand that participants will want to know this information as soon as possible, but we also must ensure accuracy of the database and adherence to the ACTG unblinding SOP which indicates that unblinding occurs once the data are complete. For REPRIEVE this will be in November 2023.
2Should participants stay on study product until their study termination visit?
Yes, participants should continue the study product until their study termination visit.
3I have a participant who will run out of study product before their study termination visit, should I dispense additional study product so they do not run out?
Yes, participants must remain on study product until their study termination visit. Please dispense additional study product to any participants who may run out of study product before their study termination visit.
4Should participants be instructed to bring back their last bottle(s) of study medication at the final visit?
It is not required that participants return dispensed study product. Product does not need to be collected once it has been dispensed or shipped to a participant. If you have instructed participants to bring in used and unused product this is okay but it is not absolutely necessary.
5Do we send the study product that participant brought back to NIAID Clinical Research Products Management Center (CRPMC)?
The instructions about returning study product are in the Letter to Pharmacists that was distributed to sites with the study closure announcement.
6When should study product be returned to the CRPMC (domestic or US sites) or destroyed on site using a DAIDS Authorized Witness (DAW) visit (international or non-US sites)?
Study product should be destroyed or returned to the CRPMC only after all participants have completed their study termination visit. Participants should continue taking study product until they attend their termination visit. Site pharmacists should continue to dispense to participants that require additional study product prior to their scheduled termination visit.
7What should sites do with returned study product from participants or remaining inventory in the pharmacy?
Sites should only collect partial or full bottles from participants during the study termination visits. Partial or full bottles of study product (returned by participants or inventory at each pharmacy) should be either returned to the CRPMC using the COSMOS system (domestic or US sites) or destroyed on sites after setting up a DAW visit with the CRPMC (international or non-US sites).
8I have a participant that self-reported he stopped study product. How we should complete the form RP0003 Final Medication Status?
If the participant informs the site they had stopped study product since the last REPRIEVE visit without seeking the REPRIEVE site's input/guidance on that decision, please answer the RP0003 questions as follows:
4. Date it was determined the participant would discontinue study medication: enter the date your site learned that the participant stopped study product, i.e., the current visit date
5. Date of last known dose of study medication: enter the date the subject reported they took their last dose of study product
6. Did the participant complete treatment as defined by the protocol, or at the time of official study closure? If the date of the participant’s last dose was before the REPRIEVE study closure announcement, enter NO. If the date of the participant’s last dose was after the REPRIEVE the study closure announcement, enter YES.
4. Date it was determined the participant would discontinue study medication: enter the date your site learned that the participant stopped study product, i.e., the current visit date
5. Date of last known dose of study medication: enter the date the subject reported they took their last dose of study product
6. Did the participant complete treatment as defined by the protocol, or at the time of official study closure? If the date of the participant’s last dose was before the REPRIEVE study closure announcement, enter NO. If the date of the participant’s last dose was after the REPRIEVE the study closure announcement, enter YES.
9What are the expectations for documentation of accountability when participants return unused IP?
Site pharmacists should reconcile accountability records so that the records reflect how many bottles were returned by participants.
10I have submitted the final return of study product to the CRPMC following our site's final study termination visit. Are there any further steps I need to take at this time? Do you have instructions for how to handle accountability records and other study documents going forward?
No further action is required. All pharmacy related duties and processes (such as temperature monitoring) as they relate to A5332 can be terminated at this time. Please contact the clinic staff with regards to retaining study related files.
OpenClinica, CRFs, and Data Management
1Where do I find the study termination visit in OpenClinica?
There is a new visit in OpenClinica called Study Termination that should be used to enter the information collected at the final study visit. This visit is the last visit to the right in the subject matrix screen.
2We are receiving error messages and validation checks when entering forms for the study termination visits. Can these be turned off?
Yes, we are working to remove these checks and hope to have the issue resolved in the next week (by approximately April 28th). We apologize for any inconvenience this has caused.
3How can I get in touch with the REPRIEVE Data Managers
The REPRIEVE Data Managers can be reach at reprieve.dmc@fstrf.org
4Where do we find the Vital Status and Endpoint Follow Up (VSW0025) CRF?
The CRF is in the OpenClinica Subject Matrix home screen in the in the Vital Status Follow-up Visit folder, pull the scroll bar at the bottom right until you see it.
5How do I respond to question 3 on the Off Study (RP0001) and question 6 on the Final Study Medication Status (RP0003)?
For participants who were still on study at the time of the REPRIEVE closure announcement, please:
- RP0001: answer Q3 YES and STOP per that form's instructions.
(Q4 is answered ONLY for participants who had prematurely discontinued REPRIEVE and went off study BEFORE the REPRIEVE study closure announcement).
- RP0003: answer Q6 (Did the subject complete treatment as defined by the protocol, or at the time of official study closure?) YES for participants who were still on study product at the time of the REPRIEVE closure announcement. If the subject was already off study product at the time of the closure announcement, answer this question NO and complete Q7.
- RP0001: answer Q3 YES and STOP per that form's instructions.
(Q4 is answered ONLY for participants who had prematurely discontinued REPRIEVE and went off study BEFORE the REPRIEVE study closure announcement).
- RP0003: answer Q6 (Did the subject complete treatment as defined by the protocol, or at the time of official study closure?) YES for participants who were still on study product at the time of the REPRIEVE closure announcement. If the subject was already off study product at the time of the closure announcement, answer this question NO and complete Q7.
Participant Appreciation
1Has the REPRIEVE Clinical Coordinating Center developed any materials that we can share with participants to show appreciation for their contributions to the study?
The Clinical Coordinating Center has developed an end-of-study appreciation package for REPRIEVE participants which includes the 2023 REPRIEVE Participant Newsletter, REPRIEVE Participant Certificate of Appreciation, and a REPRIEVE lapel pin. You can download the newsletter and certificate of appreciation by clicking on the links below, and these items can be shared with participants at or after their final study termination visit. If you would like to order lapel pins and/or hard copies or translations of the newsletter or certificate of appreciation, please complete the ordering form here. The Participant Newsletter has been approved by the IRB for the CCC, please submit to your local IRB/EC as per your local requirements.
Participant Appreciation Materials Ordering Form
2023 REPRIEVE Participant Newsletter - PDF | .docx (text only)
REPRIEVE Participant Certificate of Appreciation - .docx
REPRIEVE Lapel Pin - Preview
Participant Appreciation Materials Ordering Form
2023 REPRIEVE Participant Newsletter - PDF | .docx (text only)
REPRIEVE Participant Certificate of Appreciation - .docx
REPRIEVE Lapel Pin - Preview
Clinical Statin Use and Participant Guidance
1Participants at my site are wondering if they should begin taking a statin for clinical need following their participation in REPRIEVE. Do you have any guidance on how best to advise them?
The REPRIEVE Team has provided some additional guidance for site investigators and participants when discussing next steps for participants during and after the study termination visit. Please click below to download a handout with guidance for providers and a handout for participants. These documents have been approved by the IRB for the CCC, please submit to your local IRB/EC as per local requirements.
Provider Guidance Handout
Participant Guidance Handout
Provider Guidance Handout
Participant Guidance Handout
Contracting
1Do the contracts that were distributed in March 2023 need to be signed now that REPRIEVE is notified my site of study closure?
Your site’s current contract in process should not be cancelled. The current contract expires the end April and so the extension contracts need to be executed so sites can be reimbursed for study termination visits.
2The contracts include a scope of work until Month 120, should they be removed if our contract is not signed and finalized yet?
No, please sign the contract as is. Your site will not be reimbursed for any visits that are not performed, but the contract allows for the extension of the trial so that your site can be reimbursed for study termination visits.