Hypertension on Chronic Maintenance Hemodialysis Clinical Trial
Official title:
the Effect of Nifedipine Controlled Release Tablets in Hypertensive Patients on Chronic Maintenance Hemodialysis and the Influence of Hemodialysis on the Plasma Concentration of Nifedipine
This is a prospective, open, non-randomized, non-controlled study. 20 patients with
hypertension on chronic maintenance hemodialysis will be enrolled in the study. All patients
had mild to moderate hypertension and are receiving antihypertensive agents.
This study was designed to investigate effects of Adalat GITS on hemodialytic blood
pressures in patients with chronic hemodialysis by using ABPM and measuring the drug plasma
concentrations. For the purpose of investigating the influence of hemodialysis on the drug
plasma concentration as well as its efficacy, it should be necessary to assign the subjects
with the Adalat monotherapy. Since most patients in the hemodialysis center will be those
who need and already receive combination therapy, it would be practical to start Adalat
60mg/day monotherapy to remain similar antihypertensive effect when discontinuing the
previous treatment in this study population to be screened and enrolled. And taking into the
consideration of clinical practice, few patients undergoing hemodialysis could be well
controlled by low dose Adalat 30mg/day alone. So this study will evaluate the effect and
safety of Adalat GITS 60mg/day alone and thereafter the influence of hemodialysis on the
drug plasma concentration without any other possible drug interaction. The agents are given
orally once a day at 08:00h and patients are followed for at least 4 weeks. After that,the
patients whose blood pressure are well controlled by Adalat GITS 60mg/day by office blood
pressure would be enrolled for further ABPM assessment and plasma concentration evaluation.
Calcium channel blockers are widely used to reduce blood pressure in hypertensive patients
on hemodialysis. They are useful I patients with left ventricular hypertrophy, diastolic
dysfunction and stable angina pectoris. Adalat GITS, a long-acting dihydropyridine calcium
channel blocker, has been used as one of first choices to treat the hypertension because of
its effective hypotensive potency and relative absence of side effects compared with the
short-acting agent. Antihypertensive effects of calcium channel blockers largely depend on
their plasma concentrations, a rapid increase in blood pressure may occur as circulating
levels of such blockers decrease after hemodialysis. This rapid fluctuation in blood
pressure may evoke rapid alteration in hemodynamics. Luik et al. show that pre- or
post-dialysis blood pressure measurements in patients with hemodialysis may be misleading
for determining the blood pressure. Ambulatory pressure monitoring (ABPM) may be more useful
for estimating blood pressure control in the dialysed patients. For most patients on
dialysis, the goal office blood pressure is less than an average value below 150/90 mmHg on
no medication. The reasonable target goal of mean ambulatory blood pressure is less than
135/85 mmHg during the day and less than 120/80 mmHg at night.
There is need of more convincing data to demonstrate the effect of Adalat GITS on
hemodialytic patients by using ABPM and investigating the plasma concentrations. This study
was designed to investigate effects of Adalat GITS on hemodialytic blood pressures in
patients with chronic hemodialysis by using ABPM and measuring the drug plasma
concentrations.
This is a prospective, open, non-randomized, non-controlled study. 20 patients with
hypertension on chronic maintenance hemodialysis will be enrolled in the study. All patients
had mild to moderate hypertension and are receiving antihypertensive agents.
All antihypertensive agents received by patients screened were withdrawn and patients are
assigned to receive only nifedipine controlled release tablets 60mg/day. The agents are
given orally once a day at 08:00h and patients are followed for at least 4 weeks. After 4
weeks of antihypertensive treatment, 20 patients with adequate blood pressure achieved
(pre-hemodialysis office blood pressure < 140/90 mmHg) will be recruited into the study. If
adequate blood pressure is not achieved, the patients will be excluded.
After patients have achieved adequate blood pressure (pre-hemodialysis office blood pressure
< 140/90 mmHg) at enrollment, 24-hour ambulatory blood pressure monitoring (ABPM) is
immediately performed on the day of hemodialysis within the subsequent two days. The
administration of Adalat will continue as previously until the morning of the hemodialytic
day with AMPM and blood samplings for study. The blood was sampled just before, 1 hour
after, 2 hour after and 3 hour after the start of hemodialysis, and immediately after
hemodialysis to measure circulating levels of nifedipine and the corresponding time points
on the next hemodialysis-free day.
The 24-hour ABPM is performed in each enrolled patient on the day of hemodialysis. The
monitoring is started at 08:00 h when the drugs are given. The device is programmed to
measure blood pressure every 30 min (from 08:00 h to 21:00 h) and every 60 min (from 21:00 h
to 08:00 h).
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Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label