1. Implementation of a Three-Stage Recruitment Tracking System in the Blood Pressure in Hemodialysis (BID) Pilot Randomized Clinical Trial comparing Systolic Blood Pressure Level treatment arms
Jennifer Gassman, Dana Miskulin, Philip Zager, David Ploth, Manisha Jhamb, Lavinia Negrea, Mahboob Rahman, Cynthia Kendrick, Karen Brittain, Susan Sherer
Introduction
Screening
Baseline
Reason why those eligible to enter Baseline
were not randomized
Number
(percent)
Inability to achieve the lower limit of the high
SDUSBP goal (155 mm Hg) despite back titration
65 (42%)
Participant changed his or her mind
38 (25%)
Judged unlikely to achieve goals
9 (6%)
Contraindication to MRI
6 (4%)
Could not perform required procedures
Other
31 (20%)
Total
155
BID Study enrollment took place over four years, from December 2011 to January Study Coordinators at the five participating clinical centers logged Stage 1 reasons why patients were not approached and kept local tallies that showed that 387 participants were approached by the study coordinators and asked to consent to the BID Pilot Study.
Of those approached for consent, 125 refused, and study coordinators kept local Stage 2 tallies of reasons for refusal. (These data could not be entered in the study database for individual because the patients had not consented.) Local tallies were summarized quarterly and presented annually at Steering Committee meetings. Reasons patients couldn’t be approached or wouldn’t consent were discussed and evaluated, with a mind toward a future Phase III randomized clinical trial. Major reasons that patients refused to consent for the BID Pilot Study included perception of study being burdensome, n=34 (27%), unwillingness to participate in research, n=14 (11%), and reluctance to change medications/goals, n=10 (8%).
A total of 281 patients consented and enrolled in the BID Pilot Study Baseline, during which SDUSBP was measured prior to each dialysis session. Participants did home blood pressure measurements weekly (3x morning and 3x afternoon) and did at least one 24-hour Ambulatory Blood Pressure measurements.
Medications were back-titrated until a 2-week running mean pre- dialysis standardized systolic BP>155 mmHg was demonstrated. 126 participants were found to be eligible (verified through an online “ready to randomize” program that checked all baseline requirements against the study’s Oracle database at the Cleveland Clinic) and were randomized.
Of the 155/281 (55%) participants who entered Baseline but were not randomized, the most common reason noted was the combination of unwillingness to back-titrate and/or inability to achieve the lower limit of the control arm SDUSBP goal (155 mm Hg) despite back-titration, which occurred in 65/155 (42%) participants. Detailed reasons are shown below, with major reasons summarized on the right.
The optimal blood pressure target for patients on hemodialysis is unknown. The Blood Pressure in Hemodialysis (BID) Pilot randomized clinical trial is an NIDDK/Dialysis Clinic, Inc., multi-center pilot study in which hypertensive hemodialysis patients are randomized to a standardized pre-dialysis Systolic BP of
vs mmHg.
126 participants on three-times-weekly dialysis were randomized at 21 dialysis units (with a census of patients) associated with five clinical centers (University of New Mexico; Tufts University; Medical University of South Carolina; University of Pittsburgh; and Case Western Reserve University/University Hospitals) and followed for one year. The Data Coordinating Center is in the Department of Quantitative Health Sciences at the Cleveland Clinic. The goals of the BID Pilot Study were to assess the feasibility and safety of randomizing participants to the systolic blood pressure treatment arms and to inform the design of a full-scale trial. Outcomes included protocol adherence, achievement of randomized SDUSBP goals by 2-week running means, and changes in LV mass by cardiac MRI.
BID recruitment was expected to be challenging, and study coordinators kept standardized local logs of reasons by stage of recruitment, with reasons for Stage 1 “Why not asked?” tracked for local dialysis unit patients apparently eligible who were not approached, and Stage 2 “Why refused?” tracked for those approached who refused consent.
281 of 387 patients approached consented and enrolled in the BID Study Baseline, which included
Standardized Blood Pressure measured (pre-cannulation) before each dialysis session
At least one day with Home Blood Pressure measured 3x morning and 3x afternoon
At least one 24-hour Ambulatory Blood Pressure Measurement
Cardiac MRI
Demonstration of hypertension (with back titration of antihypertensives until running mean systolic >155 mmHg)
Only 126/281 (45%) of those who enrolled in Baseline were randomized. Stage 3 Recruitment tracking included collecting Baseline dropout data on reasons enrolled patients were not randomized. Three-stage recruitment tracking helped identify barriers at each stage of the challenging recruitment process.
Discussion and Future Plans
Recruitment was challenging in BID, with less than half of those enrolling in Baseline proceeding to randomization. Cumulative Stage 3 reasons for baseline dropouts were included in each weekly report and were presented along with quarterly Stage 1 “Why not asked?” and Stage 2 “Why refused” reasons on coordinator calls and at Steering Committee and DSMB calls/meetings. Study coordinators kept track of the patients at dialysis units associated with their clinical centers, and patients who had previously been considered ineligible were reconsidered if reasons for exclusion changed.
Investigators used recruitment tracking data to brainstorm ways to improve approach, consent, and randomization rates during the Pilot Study and to plan design changes enabling higher recruitment yields for a subsequent full-scale study. The BID Study’s sample size goal of 120 randomized patients was exceeded, with a total of 126 randomized. BID Follow up ended in early Two-week running means of 144 ± 17.5 mm Hg vs. 155 ± 15.4 mm Hg (mean ± SD) were achieved at day 330, showing a separation of 11 mmHg. Retention was excellent. The goal for completing standardized pre-dialysis blood pressure measurements was exceeded. The goal for obtaining ambulatory blood pressure measurements was at target. Fewer home blood pressure measurements than expected were successfully completed, a result similar to that seen in the Frequent Hemodialysis Network Nocturnal Study. BID investigators are currently working on the results paper and writing a protocol for a full-scale Phase III trial. The Phase III trial will not require cardiac MRI and will feature a simplified protocol. BID investigators are enthusiastic, energized by the success of the BID Pilot Study in showing feasibility and by the results of the SPRINT Study.
Stage 1. Local Site Tally
Reasons some candidates were not approached
Only dialyzes twice a week
Will soon be doing PD/ nocturnal/ home dialysis
Will soon receive a transplant
Patient is concerned about his arm or vascular access
Known to be substance abuser
Known to be non-compliant to dialysis treatments or time
Known to be non-compliant to fluid intake
Known to be non-compliant to antihypertensive meds
Can’t measure his/her BP in his/her upper arm
SDU BP < 140 mmHg on no meds or minimal meds
Blood Pressures not under 140 but seem too low
Too large to fit in an MRI machine
Metal in body precludes measurement of MRI
Other contra indication to MRI (list it)
Seems to have very frequent hospitalizations
Thought to have a short life expectancy (list why)
Blind
Other comorbidity (list)
Cognitive impairment
Speaks a language our site does not support (list language)
Patient known to not to want to participate
Primary care doc/nephrologist known not to want pt to participate
Patient has no family support
Enrolled or about to enroll in another intervention study
Plans to switch to a non BID unit nearby (list unit)
Plans to move to a new city
Incarcerated
Nursing Home
Stage 3. Local Site Tally
Reasons approached candidates did not consent
Likes current BP control and meds, does not want to change them
Not willing to do MRIs
Not willing to do another requirement (keep track of requirement)
Concerned about arm / vascular access
Do not trust doctors, research, “feels like a human guinea pig”
Other specific reason does not want to participate (track reason)
Significant others do not support patient participating
Primary care Dr, other nephrologist do not support participating
Says that study requirements overall are just too much for him/her
Not ready at this time / Thinking about it / Will approach later
Stage 3 “Baseline Dropout” Results
Primary reason patient not randomized n
(% of 155)
Final baseline BP not in range, too low
60 (38.7%)
Final baseline BP not in range, too high
2 (1.3%)
Patient arm(s) can no longer be used to measure BP
1 (0.6%)
Excessive intradialytic hypotension
Excessive post-HD hypotension
Unable to sustain BP>155 mmHg SDUBPM
4 (2.6%)
Patient arms med condition related to past vascular accesses
Patient size prevented fitting into the MRI machine
Unable to have baseline MRI, other reason
5 (3.2%)
Patient had an acute MI during baseline
Patient had unstable angina during baseline
Patient admitted to acute or chronic car
Alcohol or substance abuse detected
Other medical reason
6 (3.9%)
Team decision: patient would not adhere to BP meds
Team decision: patient would not adhere to protocol
8 (5.2%)
Patient changed mind, dislikes in-center BP measurement
9 (5.8%)
Patient changed mind, dislikes cardiac MRI
Patient changed mind, dislikes home BP measurements
Patient changed mind, protocol burdensome
16 (10.3%)
Patient changed mind, other reason
10 (6.5%)
Family/significant other do not support
Patient switched to in-center nocturnal
Patient changed mind, doesn't want to be randomized
Patient could/would not do required baseline home measures
Patient could/would not do required ABPM
Patient switching to non-BID dialysis unit
Patient will receive a living donor kidney
The BID Pilot Study
is supported by
NIDDK R01DK and Dialysis Clinic, Inc.