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This is a prospective, randomized, placebo controlled, multi-center clinical trial to determine whether aliskiren or aliskiren plus losartan or enalapril plus losartan effects on peritoneal membrane transportation.
Detailed description:
Many peritoneal dialysis patients suffer from uremia due to inadequate dialysis or volume overload caused by failure of peritoneal membrane transportation. One of the most important etiologies of peritoneal membrane failure is unavoidable to use high glucose-containing dialysate solution that induces injury to mesothelial cells. Previous data found that injured mesothelial cell produced Angiotensin II inducing peritoneal inflammation and fibrosis. Blockade of the renin-angiotensin system by angiotensin-converting enzyme inhibition or angiotensin receptor antagonism play a major role to slow these effects.
Many trials in animal studies have proved the benefit of angiotensin-converting enzyme inhibition and angiotensin receptor antagonism in preservation of peritoneal membrane but clinical evidences in human are controversy in the past. Recently our data have demonstrated the roles of angiotensin-converting enzyme inhibition and angiotensin receptor antagonism for slowing peritoneal membrane dysfunction in views of anatomy and solute transportation (abstract presentation in American Society of Nephrology 2010). These available data confirmed that renin-angiotensin system blockages were benefit. Nowadays, there is a new class of antihypertensive drug, called direct renin inhibitor . It blocks (pro)renin active site that is the rate- limiting step of renin-angiotensin system. We're interesting in this drug and wonder it can slow the peritoneal membrane dysfunction in continuous ambulatory peritoneal dialysis patients. Therefore, we design a study to show the effect of aliskiren alone or combination with angiotensin receptor antagonism for slowing peritoneal membrane dysfunction in naive continuous ambulatory peritoneal dialysis patients in several hospitals. Our study will be taken in 1 year duration and uses modified peritoneal equilibrium test and dialysate cancer antigen 125 (CA125) as indexes of peritoneal membrane transportations.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Aliskiren | Active Comparator |
| |
| Aliskiren plus Losartan | Active Comparator |
| |
| Enalapril plus Losartan | Active Comparator |
| |
| placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| placebo | Drug | Patients in the control group will administer antihypertensive agents, except angiotensin converting enzyme inhibitors, angiotensin receptor blockers and spironolactone. Dosages are adjusted appropriately to achieve and maintain the target blood pressure of 130/80 mmHg |
| Measure | Description | Time Frame |
|---|---|---|
| Changing in modified peritoneal equilibrium test | Modified peritoneal equilibrium test is the standard test for evaluation peritoneal membrane transportation. | at the beginning, 6 months and 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| appearance rate of dialysate CA125 | Appearance rate of dialysate CA125 refers to anatomical change of peritoneal. It can be calculated by multiplying dialysate CA125 with dialysate volume and deviding by dwell time. | the begining, 6 months and 12 months |
| nutritional status |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Talerngsak Kanjanabuch, Assist. Prf. | Contact | 662-2564321 | 211 | golfnephro@hotmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Talerngsak Kanjanabuch, Assist. Prf. | Investigator | Principal Investigator |
| Pichaya Tantiyavarong, MD. | Chulalongkorn University | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chulalongkorn University | Recruiting | Bangkok | 10330 | Thailand |
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| ID | Term |
|---|---|
| C446481 | aliskiren |
| D019808 | Losartan |
| D004656 | Enalapril |
| ID | Term |
|---|---|
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
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|
|
| Aliskiren | Drug | Patients with hypertension will take fixed-dose 150 mg aliskiren per day. Antihypertensive agents other than angiotensin converting enzyme inhibitors, angiotensin receptor blocker and spironolactone will be allowed and dosages are adjusted appropriately to achieve and maintain the target blood pressure of 130/80 mmHg |
|
|
| Aliskiren plus Losartan | Drug | Patients with hypertension will take fixed-dose 150 mg aliskiren + 50 mg losartan per day. Antihypertensive agents other than angiotensin converting enzyme inhibitors, angiotensin receptor blockers and spironolactone will be allowed and dosages are adjusted appropriately to achieve and maintain the target blood pressure of 130/80 mmHg |
|
|
| Enalapril plus Losartan | Drug | Patients with hypertension will take fixed-dose 20 mg enalapril + 50 mg losartan per day. Antihypertensive agents other than angiotensin converting enzyme inhibitors, angiotensin receptor blockers and spironolactone will be allowed and dosages are adjusted appropriately to achieve and maintain the target blood pressure of 130/80 mmHg |
|
|
assess by serum albumin and subjective global assessment |
| at the beginning, 6 months and 12 months |
| adverse events | adverse events of the drugs | 12 months |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013777 | Tetrazoles |
| D004151 | Dipeptides |
| D009842 | Oligopeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |