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Trial registered on ANZCTR


Registration number
ACTRN12615001322527
Ethics application status
Approved
Date submitted
5/10/2015
Date registered
2/12/2015
Date last updated
12/08/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of angiotensin receptor blockers on blood pressure control among euvolemic hypertensive hemodialysis patients: a randomized controlled trial
Scientific title
Effect of angiotensin receptor blockers on blood pressure control among euvolemic hypertensive hemodialysis patients: a randomized controlled trial
Secondary ID [1] 287593 0
nil
Universal Trial Number (UTN)
nil
Trial acronym
nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
hypertension in End stage renal disease 296393 0
Condition category
Condition code
Renal and Urogenital 296664 296664 0 0
Kidney disease
Cardiovascular 296665 296665 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1. The intervention group, on top of standard antihypertensive medication (calcium channel blocker, alpha and beta blocker) will receive ARB (losartan) among post dialysis euvolumic hypertensive patients.

2. The ARB used for current RCT is “Losartan”. The selection of Losartan was based on availability, cost effectiveness and expert opinion of a Nephrologist and a cardiologist. Starting dose of 50 mg/day of losartan oral tablet will be given to recruited patients. Persistent high post dialysis blood pressure of >160mmHg or unable to attain targeted blood pressure of 140mmHg for a period of four months, upon consultation with a cardiologist and nephrologists the dose of losartan will be titrated up to 100mg/day. Moreover, based on patient response to initial 50mg/day dose, cardiologist may titrate the dose up to 100mg/day before 4 months so as to avoid any detrimental effect on subject health.(NKF KDOQI guideline 2004, to be followed for dose titration)

A person in family of the patient will be asked to monitor the adherence of given medication. contact number and frequent meeting with the designated person will be arranged with the investigator to closely monitor the adherence of medication.

3. The maximum study duration is 8 months. Since there are two intervention dose of losartan, a 4 month period of each dose (50mg/day, 100mg/day) will be allowed to note patient response. Failure to achieve and maintain targeted systolic blood pressure of <140mmHg for three weeks with 50mg/day dose during the first 4 months, the subjects will be titrated to 100mg/day for next 4 months or if study end point achieved (maintaining<140mmHg for three weeks)

4. Dose of losartan to be administered at morning after breakfast except on dialysis session days, to avoid any incidence of hypotension.
Intervention code [1] 292993 0
Treatment: Drugs
Comparator / control treatment
the control group include standard antihypertensive therapy among post dialysis euvolumic hypertensive patients. the standard antihypertensive therapy includes calcium channel blocker(felodipine 10mg/day oral tablet till the study end point or maximum period of 8 months), and beta blocker (metoprolol 50 mg/day oral tablet till the study end point or maximum period of 8 months)
Control group
Active

Outcomes
Primary outcome [1] 296274 0
the primary end point includes attaining post dialysis systolic blood pressure of <140mmHg and maintaining it for three weeks. Outcome will be assessed on proportion of patients achieving systolic blood pressure of <140mmHg for three weeks within 8 months of study duration
outcomes will be monitored by blood pressure monitoring device (automatic sphygmomanometer). Blood pressure will be monitored 30 minutes post dialysis till study end point is achieved or maximum duration of 8 months
Timepoint [1] 296274 0
All End stage renal failure patients undergoing dialysis thrice a week will be recruited for current study.. Blood pressure reading will be taken 30 mins post dialysis after every session ( thrice/week) till study end point or maximum period of 8 months
Secondary outcome [1] 318024 0
The secondary point will be all cause of mortality.
A validated data collection tool will be formed to record all patient finding related to study. in case of mortality, all patient records and consultation with the doctor will be assured to confirm the cause of mortality
Timepoint [1] 318024 0
8 months

Eligibility
Key inclusion criteria
Euvolumic patients with blood pressure more than 140/90 mmHg post dialysis will be included for the study.
On basis of expert opinion from nephrologists, patient 30-80 years were included for current study.
Finally, patients undergoing dialysis duration of at least 12 months, 2 to 3 HD sessions weekly and Patients willing to participate were included for current study.
Minimum age
30 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with amputations, neoplasm and cystic kidneys, unwilling to participated in the study.

Patients already on ARBs and Patients with symptomatic hypotension or SBP less than 110 mm Hg were excluded from the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Principal investigator, physician or the participant will have no influence of selection of any participation to any group nor will be aware of any participant receiving particular medication since unique serial number will be given to all participants by a neutral individual that will have no involvement in current study
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
computer generated co-variate adaptive randomization
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Results will be expressed as mean or percentage. Comparisons between treatment groups were made by using Student t-test or Mann-Whitney test when applicable for continuous variables and using test for categorical variables. Cumulative event curves will be created by means of Kaplan-Meier analysis, and differences between the 2 treatment groups were analyzed by using log-rank test.
Cox proportional hazards regression analyses will be performed for comparison of the 2 treatment groups after adjustment for the dynamic stratification variables (age, sex, years on dialysis, and diabetes) and center effect. These data will be presented as hazard ratios and 95% confidence intervals. Statistical significance was set at P less than 0.05. All statistical calculations will be performed using SPSS version 20.

The equation for statistical superiority

N = 2 x{(Z1-a/2 + Z1-ß )/d}2 x S

N=size per group; p=the response rate of standard treatment group; p 0= the response rate of new drug treatment group; z = the standard normal deviate for a one or two sided x; d= the real difference between two treatment effect; a clinically acceptable margin; S= Polled standard deviation of both comparison groups. power 80%, effect size is 3, statistical significance is 95%.

Calculating the sample size using mentioned equation
N= 2x((1.96+0.845)/3) 2 x 20.48
N= 35


Sample size for current study was based on statistical superiority trial (continuous data) design of Randomized control trial. Statistician helped in calculating sample size based on statistical superiority trial. The sample size for current study was 70, a 25 % drop out rate was added , hence a total of 88 patients were recruited for current study.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 7207 0
Malaysia
State/province [1] 7207 0
Kelantan

Funding & Sponsors
Funding source category [1] 292169 0
University
Name [1] 292169 0
Universit Sains Malaysia
Address [1] 292169 0
Chronic Kidney Disease Resource Centre, Hospital Universiti Sains Malaysia, 16150 kubang kerian, Kelantan, Malaysia
Country [1] 292169 0
Malaysia
Primary sponsor type
University
Name
Universiti Sains Malaysia
Address
Chronic Kidney Disease Resource Centre, Hospital Universiti Sains Malaysia, 16150 kubang kerian, Kelantan, Malaysia
Country
Malaysia
Secondary sponsor category [1] 290842 0
None
Name [1] 290842 0
NA
Address [1] 290842 0
NA
Country [1] 290842 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293641 0
Human Research Ethics Committee USM (HREC)
Ethics committee address [1] 293641 0
Universiti Sains Malaysia, Kampus Kesihatan, 16150 Kubang Kerian Kelantan, Malaysia.
Ethics committee country [1] 293641 0
Malaysia
Date submitted for ethics approval [1] 293641 0
28/05/2015
Approval date [1] 293641 0
07/09/2015
Ethics approval number [1] 293641 0
USM/JEPeM/15050173

Summary
Brief summary
Since there is a constant volume variation during hemodialysis session, there is a strong possibility for the activation of RAAS system. The activation of RAAS system leads to narrowing of the lumen of blood vessels thus leading to rise in blood pressure even if the patient is euvolumic. Considering the importance of RAAS system in euvolumic hypertensive patients, the role of drugs blocking RAAS system needs further investigation. Hence the current randomized control trial is based on role of ARBs (losartan) in managing blood pressure among euvolumic hemodialysis patients
Trial website
NA
Trial related presentations / publications
NA
Public notes
NA

Contacts
Principal investigator
Name 60786 0
Dr Amer Hayat Khan
Address 60786 0
Discipline of Clinical Pharmacy, School of Pharmacy, Universiti Sains Malaysia. 11800, Penang, Malaysia
Country 60786 0
Malaysia
Phone 60786 0
+60174106535
Fax 60786 0
Email 60786 0
dramer2006@gmail.com
Contact person for public queries
Name 60787 0
Mr Raja Ahsan Aftab
Address 60787 0
1.Discipline of Clinical Pharmacy, School of Pharmacy, Universiti Sains Malaysia. 11800, Penang, Malaysia
2. Chronic Kidney Disease Resource Centre, Hospital Universiti Sains Malaysia, 16150, Kelantan, Malaysia
Country 60787 0
Malaysia
Phone 60787 0
+60174106535
Fax 60787 0
Email 60787 0
ahsan1025@yahoo.com
Contact person for scientific queries
Name 60788 0
Dr Amer Hayat Khan
Address 60788 0
1.Discipline of Clinical Pharmacy, School of Pharmacy, Universiti Sains Malaysia. 11800, Penang, Malaysia
Country 60788 0
Malaysia
Phone 60788 0
+60174106535
Fax 60788 0
Email 60788 0
dramer2006@gmail.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary