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The optimal frequency of hemodialysis treatments in patients with incident end-stage kidney disease in not known. This pilot trial will randomize patients with incident end-stage kidney disease due to chronic kidney disease progression to two different regimens of hemodialysis: i) twice-weekly hemodialysis for six weeks with adjuvant pharmacologic medications followed by thrice-weekly hemodialysis, or ii) thrice-weekly hemodialysis. The study will test feasibility of stepwise hemodialysis, and the effects of the two regimens of hemodialysis on residual kidney function.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Hemodialysis and Pharmacologic Therapy | Experimental | Hemodialysis regimen at the initiation of dialysis treatment: Twice-weekly hemodialysis plus adjunctive pharmacologic therapy (loop diuretic, potassium-binding agent, and sodium bicarbonate) for six consecutive weeks, continued by thrice-weekly hemodialysis (intervention group) |
|
| Conventional Hemodialysis Regimen | Active Comparator | Hemodialysis regimen at the initiation of dialysis treatment: thrice-weekly hemodialysis |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hemodialysis | Other | Hemodialysis frequency will differ in the first six weeks of hemodialysis therapy between the two treatment arms. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Patients' Adherence to Study Protocol | ≥95% of participants randomized in the intervention group will adhere to the HD regimen. All participants who completed 6 and 12 months of follow-up completed interdialytic timed urine collections - Patient adherence to the study protocol was assessed by the number of participants randomized to each intervention who adhered to the study protocol and at 6 months and at 12 months | 6 months, 12 months, 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| 24-hour Urine Volume | Residual renal clearance was calculated based on 24-hour urine collection performed at baseline at enrollment; and interdialytic urine collection performed at baseline, 6 Weeks, 12 Weeks and 24 Weeks | Baseline, 6 Weeks, 12 Weeks, 24 Weeks |
| Change in Residual Kidney Function - Urea Clearance |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mariana Murea, MD | Wake Forest University Health Sciences | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Wake Forest Baptist Medical Center | Winston-Salem | North Carolina | 27157 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26498416 | Background | National Kidney Foundation. KDOQI Clinical Practice Guideline for Hemodialysis Adequacy: 2015 update. Am J Kidney Dis. 2015 Nov;66(5):884-930. doi: 10.1053/j.ajkd.2015.07.015. | |
| 7027040 | Background | Lowrie EG, Laird NM, Parker TF, Sargent JA. Effect of the hemodialysis prescription on patient morbidity: report from the National Cooperative Dialysis Study. N Engl J Med. 1981 Nov 12;305(20):1176-81. doi: 10.1056/NEJM198111123052003. |
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After study completion, de-identified participant data may be provided to other researchers in the filed if requested. The request(s) will be reviewed by the principal investigator and other study members to determine if appropriate.
2-4 months
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77 patients (41%) were approached for study participation. Of those, 51 (66%) consented to participate, resulting in 48 patients randomized to treatment with twice-weekly HD and adjuvant pharmacotherapy for 6 weeks followed by thrice-weekly HD (n = 23) or continued usual care treatment with thrice-weekly HD (n = 25).
51 patients consented to participate and enrolled for the study. 48 patients were randomized to treatment with twice-weekly HD and adjuvant pharmacotherapy for 6 weeks followed by thrice-weekly HD (n = 23) or continued usual care treatment with thrice-weekly HD (n = 25).
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| ID | Title | Description |
|---|---|---|
| FG000 | Hemodialysis and Pharmacologic Therapy | Hemodialysis regimen at the initiation of dialysis treatment: Twice-weekly hemodialysis plus adjunctive pharmacologic therapy (loop diuretic, potassium-binding agent, and sodium bicarbonate) for six consecutive weeks, continued by thrice-weekly hemodialysis (intervention group) Hemodialysis: Hemodialysis frequency will differ in the first six weeks of hemodialysis therapy between the two treatment arms. Patiromer Oral Product: Participants in the intervention group who develop hyperkalemia, during the first six weeks of receiving hemodialysis twice per week, will be treated with Patiromer. |
| FG001 | Conventional Hemodialysis Regimen | Hemodialysis regimen at the initiation of dialysis treatment: thrice-weekly hemodialysis Hemodialysis: Hemodialysis frequency will differ in the first six weeks of hemodialysis therapy between the two treatment arms. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Hemodialysis and Pharmacologic Therapy | Hemodialysis regimen at the initiation of dialysis treatment: Twice-weekly hemodialysis plus adjunctive pharmacologic therapy (loop diuretic, potassium-binding agent, and sodium bicarbonate) for six consecutive weeks, continued by thrice-weekly hemodialysis (intervention group) Hemodialysis: Hemodialysis frequency will differ in the first six weeks of hemodialysis therapy between the two treatment arms. Patiromer Oral Product: Participants in the intervention group who develop hyperkalemia, during the first six weeks of receiving hemodialysis twice per week, will be treated with Patiromer. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Patients' Adherence to Study Protocol | ≥95% of participants randomized in the intervention group will adhere to the HD regimen. All participants who completed 6 and 12 months of follow-up completed interdialytic timed urine collections - Patient adherence to the study protocol was assessed by the number of participants randomized to each intervention who adhered to the study protocol and at 6 months and at 12 months | Participants were censored at death, HD withdrawal, or conversion to peritoneal dialysis. Not included in data analysis were participants who withdrew consent, were withdrawn from the study because of nonadherence to HD treatments, or were lost to follow-up. | Posted | Count of Participants | Participants | 6 months, 12 months, 24 months |
|
Monthly basis up to Year 2
Three patients from the conventional group were excluded from the analysis due to insufficient data resulting from early consent withdrawal, non-compliance with HD due to no-show, and loss to follow-up. In addition, one patient from the incremental group was also not included in the analysis due to consent withdrawal.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Hemodialysis and Pharmacologic Therapy | Hemodialysis regimen at the initiation of dialysis treatment: Twice-weekly hemodialysis plus adjunctive pharmacologic therapy (loop diuretic, potassium-binding agent, and sodium bicarbonate) for six consecutive weeks, continued by thrice-weekly hemodialysis (intervention group) Hemodialysis: Hemodialysis frequency will differ in the first six weeks of hemodialysis therapy between the two treatment arms. Patiromer Oral Product: Participants in the intervention group who develop hyperkalemia, during the first six weeks of receiving hemodialysis twice per week, will be treated with Patiromer. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| hospitalization | Cardiac disorders | MedDRA 10.0 | Systematic Assessment | Cardiovascular |
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Our results should be interpreted in the context of several limitations. Given (1) the imbalances in baseline characteristics between the 2 groups, (2) the small sample size, and (3) the time-delineated twice-weekly HD, the effect estimates are solely exploratory. Our testing of a time-delineated prescription of twice-weekly HD for 6 weeks may leave lingering concerns as to whether incremental HD with longer periods of twice-weekly HD can be effectively and safely implemented.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Zhidong Lin | Wake Health | 3367138720 | zlin@wakehealth.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 11, 2021 | Apr 26, 2023 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | May 7, 2021 | Jun 7, 2023 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| ID | Term |
|---|---|
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D006435 | Renal Dialysis |
| ID | Term |
|---|---|
| D017582 | Renal Replacement Therapy |
| D013812 | Therapeutics |
| D016060 | Sorption Detoxification |
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| Patiromer Oral Product | Drug | Participants in the intervention group who develop hyperkalemia, during the first six weeks of receiving hemodialysis twice per week, will be treated with Patiromer. |
|
Residual renal clearance was calculated based on 24-hour urine collection performed at baseline at enrollment; and interdialytic urine collection performed during weeks 6, 12, and 24. |
| Baseline, 6 Weeks, 12 Weeks, 24 Weeks |
| Change in Residual Kidney Function - Creatinine Clearance | Residual renal clearance was calculated based on 24-hour urine collection performed at baseline at enrollment; and interdialytic urine collection performed during weeks 6, 12, and 24. | Baseline, 6 Weeks, 12 Weeks, 24 Weeks |
| 12490682 | Background | Eknoyan G, Beck GJ, Cheung AK, Daugirdas JT, Greene T, Kusek JW, Allon M, Bailey J, Delmez JA, Depner TA, Dwyer JT, Levey AS, Levin NW, Milford E, Ornt DB, Rocco MV, Schulman G, Schwab SJ, Teehan BP, Toto R; Hemodialysis (HEMO) Study Group. Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med. 2002 Dec 19;347(25):2010-9. doi: 10.1056/NEJMoa021583. |
| 11961019 | Background | Paniagua R, Amato D, Vonesh E, Correa-Rotter R, Ramos A, Moran J, Mujais S. Effects of increased peritoneal clearances on mortality rates in peritoneal dialysis: ADEMEX, a prospective, randomized, controlled trial. J Am Soc Nephrol. 2002 May;13(5):1307-1320. doi: 10.1681/ASN.V1351307. |
| 12846762 | Background | Lo WK, Ho YW, Li CS, Wong KS, Chan TM, Yu AW, Ng FS, Cheng IK. Effect of Kt/V on survival and clinical outcome in CAPD patients in a randomized prospective study. Kidney Int. 2003 Aug;64(2):649-56. doi: 10.1046/j.1523-1755.2003.00098.x. |
| 28514305 | Background | Li Y, Jin Y, Kapke A, Pearson J, Saran R, Port FK, Robinson BM. Explaining trends and variation in timing of dialysis initiation in the United States. Medicine (Baltimore). 2017 May;96(20):e6911. doi: 10.1097/MD.0000000000006911. |
| 29270499 | Background | Chin AI, Appasamy S, Carey RJ, Madan N. Feasibility of Incremental 2-Times Weekly Hemodialysis in Incident Patients With Residual Kidney Function. Kidney Int Rep. 2017 Jun 21;2(5):933-942. doi: 10.1016/j.ekir.2017.06.005. eCollection 2017 Sep. |
| 19019171 | Background | Lin YF, Huang JW, Wu MS, Chu TS, Lin SL, Chen YM, Tsai TJ, Wu KD. Comparison of residual renal function in patients undergoing twice-weekly versus three-times-weekly haemodialysis. Nephrology (Carlton). 2009 Feb;14(1):59-64. doi: 10.1111/j.1440-1797.2008.01016.x. Epub 2008 Nov 19. |
| 25171342 | Background | Zhang M, Wang M, Li H, Yu P, Yuan L, Hao C, Chen J, Kalantar-Zadeh K. Association of initial twice-weekly hemodialysis treatment with preservation of residual kidney function in ESRD patients. Am J Nephrol. 2014;40(2):140-50. doi: 10.1159/000365819. Epub 2014 Aug 23. |
| 20605303 | Background | Shafi T, Jaar BG, Plantinga LC, Fink NE, Sadler JH, Parekh RS, Powe NR, Coresh J. Association of residual urine output with mortality, quality of life, and inflammation in incident hemodialysis patients: the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) Study. Am J Kidney Dis. 2010 Aug;56(2):348-58. doi: 10.1053/j.ajkd.2010.03.020. Epub 2010 Jun 3. |
| 15034110 | Background | Termorshuizen F, Dekker FW, van Manen JG, Korevaar JC, Boeschoten EW, Krediet RT; NECOSAD Study Group. Relative contribution of residual renal function and different measures of adequacy to survival in hemodialysis patients: an analysis of the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD)-2. J Am Soc Nephrol. 2004 Apr;15(4):1061-70. doi: 10.1097/01.asn.0000117976.29592.93. |
| 21030575 | Background | Marquez IO, Tambra S, Luo FY, Li Y, Plummer NS, Hostetter TH, Meyer TW. Contribution of residual function to removal of protein-bound solutes in hemodialysis. Clin J Am Soc Nephrol. 2011 Feb;6(2):290-6. doi: 10.2215/CJN.06100710. Epub 2010 Oct 28. |
| 25415805 | Background | Weir MR, Bakris GL, Bushinsky DA, Mayo MR, Garza D, Stasiv Y, Wittes J, Christ-Schmidt H, Berman L, Pitt B; OPAL-HK Investigators. Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N Engl J Med. 2015 Jan 15;372(3):211-21. doi: 10.1056/NEJMoa1410853. Epub 2014 Nov 21. |
| 26172895 | Background | Bakris GL, Pitt B, Weir MR, Freeman MW, Mayo MR, Garza D, Stasiv Y, Zawadzki R, Berman L, Bushinsky DA; AMETHYST-DN Investigators. Effect of Patiromer on Serum Potassium Level in Patients With Hyperkalemia and Diabetic Kidney Disease: The AMETHYST-DN Randomized Clinical Trial. JAMA. 2015 Jul 14;314(2):151-61. doi: 10.1001/jama.2015.7446. |
| 26459796 | Background | Pitt B, Bakris GL, Bushinsky DA, Garza D, Mayo MR, Stasiv Y, Christ-Schmidt H, Berman L, Weir MR. Effect of patiromer on reducing serum potassium and preventing recurrent hyperkalaemia in patients with heart failure and chronic kidney disease on RAAS inhibitors. Eur J Heart Fail. 2015 Oct;17(10):1057-65. doi: 10.1002/ejhf.402. Epub 2015 Oct 12. |
| 17702709 | Background | Kovesdy CP, Regidor DL, Mehrotra R, Jing J, McAllister CJ, Greenland S, Kopple JD, Kalantar-Zadeh K. Serum and dialysate potassium concentrations and survival in hemodialysis patients. Clin J Am Soc Nephrol. 2007 Sep;2(5):999-1007. doi: 10.2215/CJN.04451206. Epub 2007 Aug 16. |
| 17699193 | Background | Wu DY, Shinaberger CS, Regidor DL, McAllister CJ, Kopple JD, Kalantar-Zadeh K. Association between serum bicarbonate and death in hemodialysis patients: is it better to be acidotic or alkalotic? Clin J Am Soc Nephrol. 2006 Jan;1(1):70-8. doi: 10.2215/CJN.00010505. Epub 2005 Nov 23. |
| 27699876 | Background | Daugirdas JT. Estimating Time-averaged Serum Urea Nitrogen Concentration during Various Urine Collection Periods: A Prediction Equation for Thrice Weekly and Biweekly Dialysis Schedules. Semin Dial. 2016 Nov;29(6):507-509. doi: 10.1111/sdi.12554. Epub 2016 Oct 4. |
| 20107428 | Background | Daugirdas JT, Depner TA, Greene T, Levin NW, Chertow GM, Rocco MV; Frequent Hemodialysis Network Trial Group. Standard Kt/Vurea: a method of calculation that includes effects of fluid removal and residual kidney clearance. Kidney Int. 2010 Apr;77(7):637-44. doi: 10.1038/ki.2009.525. Epub 2010 Jan 27. |
| 12164889 | Background | Jansen MA, Hart AA, Korevaar JC, Dekker FW, Boeschoten EW, Krediet RT; NECOSAD Study Group. Predictors of the rate of decline of residual renal function in incident dialysis patients. Kidney Int. 2002 Sep;62(3):1046-53. doi: 10.1046/j.1523-1755.2002.00505.x. |
| 36167537 | Derived | Murea M, Highland BR, Yang W, Dressler E, Russell GB. Patient-reported outcomes in a pilot clinical trial of twice-weekly hemodialysis start with adjuvant pharmacotherapy and transition to thrice-weekly hemodialysis vs conventional hemodialysis. BMC Nephrol. 2022 Sep 27;23(1):322. doi: 10.1186/s12882-022-02946-w. |
| 34933066 | Derived | Murea M, Patel A, Highland BR, Yang W, Fletcher AJ, Kalantar-Zadeh K, Dressler E, Russell GB. Twice-Weekly Hemodialysis With Adjuvant Pharmacotherapy and Transition to Thrice-Weekly Hemodialysis: A Pilot Study. Am J Kidney Dis. 2022 Aug;80(2):227-240.e1. doi: 10.1053/j.ajkd.2021.12.001. Epub 2021 Dec 18. |
| 34031117 | Derived | Murea M, Moossavi S, Fletcher AJ, Jones DN, Sheikh HI, Russell G, Kalantar-Zadeh K. Renal replacement treatment initiation with twice-weekly versus thrice-weekly haemodialysis in patients with incident dialysis-dependent kidney disease: rationale and design of the TWOPLUS pilot clinical trial. BMJ Open. 2021 May 24;11(5):e047596. doi: 10.1136/bmjopen-2020-047596. |
| 33165001 | Derived | Murea M. Precision medicine approach to dialysis including incremental and decremental dialysis regimens. Curr Opin Nephrol Hypertens. 2021 Jan;30(1):85-92. doi: 10.1097/MNH.0000000000000667. |
| Switched to thrice-weekly HD |
|
| Switched to Peritoneal Dialysis |
|
| Lost to Follow-up |
|
| Non-compliance with HD |
|
| BG001 | Conventional Hemodialysis Regimen | Hemodialysis regimen at the initiation of dialysis treatment: thrice-weekly hemodialysis Hemodialysis: Hemodialysis frequency will differ in the first six weeks of hemodialysis therapy between the two treatment arms. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Body mass index | Mean | Standard Deviation | kg/m^2 |
|
| Body surface area | Mean | Standard Deviation | m^2 |
|
| OG001 | Conventional Hemodialysis Regimen | Hemodialysis regimen at the initiation of dialysis treatment: thrice-weekly hemodialysis Hemodialysis: Hemodialysis frequency will differ in the first six weeks of hemodialysis therapy between the two treatment arms. |
|
|
| Secondary | 24-hour Urine Volume | Residual renal clearance was calculated based on 24-hour urine collection performed at baseline at enrollment; and interdialytic urine collection performed at baseline, 6 Weeks, 12 Weeks and 24 Weeks | Participants were censored at death, HD withdrawal, or conversion to peritoneal dialysis. Not included in data analysis were participants who withdrew consent, were withdrawn from the study because of nonadherence to HD treatments, or were lost to follow-up. | Posted | Least Squares Mean | 95% Confidence Interval | mL/day | Baseline, 6 Weeks, 12 Weeks, 24 Weeks |
|
|
|
| Secondary | Change in Residual Kidney Function - Urea Clearance | Residual renal clearance was calculated based on 24-hour urine collection performed at baseline at enrollment; and interdialytic urine collection performed during weeks 6, 12, and 24. | Participants were censored at death, HD withdrawal, or conversion to peritoneal dialysis. Not included in data analysis were participants who withdrew consent, were withdrawn from the study because of nonadherence to HD treatments, or were lost to follow-up. | Posted | Least Squares Mean | 95% Confidence Interval | mL/min/1.73m^2 | Baseline, 6 Weeks, 12 Weeks, 24 Weeks |
|
|
|
| Secondary | Change in Residual Kidney Function - Creatinine Clearance | Residual renal clearance was calculated based on 24-hour urine collection performed at baseline at enrollment; and interdialytic urine collection performed during weeks 6, 12, and 24. | Participants were censored at death, HD withdrawal, or conversion to peritoneal dialysis. Not included in data analysis were participants who withdrew consent, were withdrawn from the study because of nonadherence to HD treatments, or were lost to follow-up. | Posted | Least Squares Mean | 95% Confidence Interval | mL/min/1.73m^2 | Baseline, 6 Weeks, 12 Weeks, 24 Weeks |
|
|
|
| 1 |
| 22 |
| 11 |
| 22 |
| 0 |
| 22 |
| EG001 | Conventional Hemodialysis Regimen | Hemodialysis regimen at the initiation of dialysis treatment: thrice-weekly hemodialysis Hemodialysis: Hemodialysis frequency will differ in the first six weeks of hemodialysis therapy between the two treatment arms. | 6 | 22 | 12 | 22 | 0 | 22 |
| Hospitalization | Vascular disorders | MedDRA 10.0 | Systematic Assessment | Cerebrovascular |
|
| hospitalization | General disorders | MedDRA 10.0 | Systematic Assessment | Fluid manageme |
|
| hospitalization | General disorders | MedDRA 10.0 | Systematic Assessment | Hyperkalemia |
|
| hospitalization | Nervous system disorders | MedDRA 10.0 | Systematic Assessment | Encephalopathy |
|
| hospitalization | Infections and infestations | MedDRA 10.0 | Systematic Assessment | Vascular access infection |
|
| hospitalization | General disorders | MedDRA 10.0 | Systematic Assessment | Vascular access complication, noninfectious |
|
| hospitalization | Infections and infestations | MedDRA 10.0 | Systematic Assessment | Infection, not related to vascular access |
|
| hospitalization | General disorders | MedDRA 10.0 | Systematic Assessment | other |
|
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| D052801 | Male Urogenital Diseases |
| Urine volume at Week 6 |
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| Urine volume at 12 weeks |
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| Urine volume at 24 Weeks |
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| Week 6 Renal Urea Clearance |
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| Week 12 Renal Urea Clearance |
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| Week 24 Renal Urea Clearance |
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| Week 6 Renal Creatinine Clearance |
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| Week 12 Renal Creatinine Clearance |
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| Week 24 Renal Creatinine Clearance |
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