Recognizing & Correcting the Problem of Hypertension in FSGS Clinical Subjects

A recent review of enrollment and follow-up data in the FSGS Clinical Trial unexpectedly revealed that nearly thirty percent of the subjects at the initiation of the study had either moderate or severe hypertension.

Blood Pressure at Study Initiation: Prior to 11/06

Because severe hypertension may significantly impact outcomes and could complicate the assessment of treatment effect, the Clinical Management Committee (CMC) has developed new policies to achieve better blood pressure control.

The scope of the problem

A review of the data for subjects enrolled in the study prior to November 1, 2006 revealed that a third had moderate or severe hypertension at baseline. At baseline, the mean blood pressure elevation over target range was 16.4 +/- 10.8 mmHg and 14.5 +/- 14.0 mmHg for systolic and diastolic blood pressures respectively. Moderate hypertension was defined as systolic or diastolic blood pressures greater than 95th percentile (target) appropriate for gender, age and height, but less than 10 mmHg above the target. Patients with blood pressures 10 mmHg above target were characterized as severely hypertensive. Adult subjects were deemed hypertensive if they met the JNC7 criteria with systolic blood pressures >140 mmHg or diastolic blood pressures >90 mmHg. By study week "0", 17 percent of the patients had moderate hypertension and 11 percent had severe hypertension.

The new requirment for normal blood pressures at study entry reduces the hypertension problem

After November 1st, when new regulations required that blood pressures needed to be normal prior to study entry, 89 percent of patients were normatensive at baseline. At the time when study drug was initiated, week "0", only 11 percent of the subjects were hypertensive. None were severely hypertensive.

Blood Pressure at Study Initiation: After 11/06

New recommendations for subject blood pressure monitoring and treatment

The October 2006 FSGS newsletter has an article regarding the blood pressure problem and potential solutions has been mailed to all research coordinators and principle investigators.

Study investigators and research coordinators entering a patient into the study will receive notification from the CMC about the high BP and will be asked about planned treatment. Blood pressures must be normalized prior to study enrollment, even if another medication is added. Once the BP is controlled, the patient can be randomized.

The CMC will review all submitted BPs during their monthly meetings. When a patient has blood pressure above target on two consecutive visits, the principal investigator at the patient's center will be contacted by the CMC and Data Collection Center (DCC). The reseach coordinator or principal investigator will need to submit adverse event (AE) form dealing with the hypertension.

Additional antihypertensive medications can be prescribed to normalize the blood pressure. However, the addition of an angiotensin receptor blocker (ARB) or increasing the dose of the angiotensin converting enzyme inhibitor above study-approved doses is not allowed.

Why is this important?

A recent research study suggested that reducing blood pressure correlated with reduced proteinuria and preservation of renal function, even in FSGS patients with marked reduction of renal excretory function¹ . By addressing subject hypertension, the impact of an important confounding variable will have been minimized. Thus the potential for  meaningful FSGS Clinical Trial conclusions based on the two treatments arms will be enhanced.

Investigators and research coordinators can contact the director of the CMC Dr Debbie Gipson (Debbie_Gipson@med.unc.edu) regarding questions or any suggestions regarding how better to recognize or treat hypertension in FSGS clinical study participants.

References

1. Futrakal, N., Sirviriyakul, P., Deekajorndej, T. Futrakul, P. Hemodynamic maladjustment and disease progression in nephrosis with FSGS. Renal Failure 26:231-6, 2004.

2. Seventh Report of the Joint National Committe on Prevention, Detection, Evaluation and Treatment of High Blood Pressure(JNC&)

3. Diagnosis, Evaluation and Treatment of High Blood Pressure in Children and Adolescents

4. JNC 7 Physicians Reference Card

5. Patient Guide to Lowering Blood Pressure

Version 1.28.2007 By: Peter Yorgin, MD, FSGS Investigator, Loma Linda University, Loma Linda, CA