氯噻酮和布美他尼治疗晚期慢性肾脏病：HEBE-CKD 试验
2020年11月4日 更新者：Fabio Solis-Jimenez、Hospital General de México Dr. Eduardo Liceaga
本研究旨在证明基于双重利尿剂的治疗对慢性肾病和严重肾小球滤过率受损患者的可能益处。 这是基于之前的观察，研究人员发现容量超负荷是该人群中的常见情况，并且与发病率和死亡率的增加密切相关。 研究人员认为，考虑到这些患者中的大多数都接受袢利尿剂治疗，这种疗法可能是有益的，但是，随着时间的推移，远端肾单位会发生适应性变化，从而导致治疗效果下降。 从这个意义上讲，适当剂量的噻嗪类利尿剂可以“打破”抵抗力，因为它们的作用机制会拮抗抵抗力机制。 不幸的是，直到今天，这种治疗还没有得到充分的评估。 特别是在这一类人群中。
研究人员开发了一项研究，建议作为双盲随机临床试验，将人群分为两组。 一组将接受基于袢利尿剂（布美他尼）的标准治疗，而另一组将接受干预（布美他尼加氯噻酮）。 在 30 天的随访期后，将对结果进行测量。
关于治疗的有效性，将测量生物阻抗引起的容量过载的减少。 同时观察同一监测期内不良反应的发生情况。
研究概览
研究类型
介入性
注册 (实际的)
34
阶段
- 阶段2
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Mexico City、墨西哥、06720
- Hospital General de Mexico
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
纳入标准：
- 肾小球滤过率小于 30 ml/min/1.73m
- 没有替代疗法（透析或血液透析）
- 音量过载
- 每天至少 100 毫升残余利尿
- 使用袢利尿剂至少一个月
排除标准：
- 利尿剂已知的过敏
- 严重感染患者
- 血流动力学不稳定的患者
- 截肢者
- 认知障碍患者
- 急性肾功能衰竭患者
- 移植物丢失患者
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：三倍
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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安慰剂比较：安慰剂
该组将接受每天 3 毫克的布美他尼，持续一周，外加模拟治疗组氯噻酮剂量的安慰剂（淀粉）。
如果剂量耐受性良好，布美他尼的剂量将增加至每天 4 毫克。
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布美他尼
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实验性的：治疗组
该组每天将接受 3 毫克的布美他尼和 50 毫克的氯噻酮，持续一周。
如果剂量耐受良好，将增加至每天4毫克布美他尼和100毫克氯噻酮。
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布美他尼
氯噻酮
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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全身水分的变化
大体时间：从基础改为第 28 天
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通过生物电阻抗分析测量，与初始测量相比
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从基础改为第 28 天
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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平均动脉压的变化
大体时间：从基础改为第 28 天
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与基线测量值相比血压下降 (mmhg)
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从基础改为第 28 天
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钠排泄分数的变化
大体时间：从基础改为第 28 天
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与基线测量相比，钠排泄分数增加
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从基础改为第 28 天
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细胞外水的变化
大体时间：从基础改为第 28 天
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通过生物电阻抗分析测量细胞外水的减少
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从基础改为第 28 天
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细胞外水/全身水比的变化
大体时间：从基础改为第 28 天
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通过生物电阻抗分析测量细胞外水/全身水比的减少
|
从基础改为第 28 天
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收缩压的变化
大体时间：从基础改为第 28 天
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从基础改为第 28 天
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舒张压的变化
大体时间：从基础改为第 28 天
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从基础改为第 28 天
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Fabio Solis-Jimenez, M.D.、Hospital General de México Dr. Eduardo Liceaga
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
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- Wong SP, Hebert PL, Laundry RJ, Hammond KW, Liu CF, Burrows NR, O'Hare AM. Decisions about Renal Replacement Therapy in Patients with Advanced Kidney Disease in the US Department of Veterans Affairs, 2000-2011. Clin J Am Soc Nephrol. 2016 Oct 7;11(10):1825-1833. doi: 10.2215/CJN.03760416. Epub 2016 Sep 22.
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- Verberne WR, Dijkers J, Kelder JC, Geers ABM, Jellema WT, Vincent HH, van Delden JJM, Bos WJW. Value-based evaluation of dialysis versus conservative care in older patients with advanced chronic kidney disease: a cohort study. BMC Nephrol. 2018 Aug 16;19(1):205. doi: 10.1186/s12882-018-1004-4.
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- Titze J. Interstitial fluid homeostasis and pressure: news from the black box. Kidney Int. 2013 Nov;84(5):869-71. doi: 10.1038/ki.2013.287.
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- Khalaf FK, Dube P, Mohamed A, Tian J, Malhotra D, Haller ST, Kennedy DJ. Cardiotonic Steroids and the Sodium Trade Balance: New Insights into Trade-Off Mechanisms Mediated by the Na(+)/K(+)-ATPase. Int J Mol Sci. 2018 Aug 30;19(9):2576. doi: 10.3390/ijms19092576.
- Maruta Y, Hasegawa T, Yamakoshi E, Nishiwaki H, Koiwa F, Imai E, Hishida A. Association between serum Na-Cl level and renal function decline in chronic kidney disease: results from the chronic kidney disease Japan cohort (CKD-JAC) study. Clin Exp Nephrol. 2019 Feb;23(2):215-222. doi: 10.1007/s10157-018-1631-x. Epub 2018 Aug 24.
- Khan YH, Sarriff A, Adnan AS, Khan AH, Mallhi TH. Chronic Kidney Disease, Fluid Overload and Diuretics: A Complicated Triangle. PLoS One. 2016 Jul 21;11(7):e0159335. doi: 10.1371/journal.pone.0159335. eCollection 2016.
- Hassinger AB, Wald EL, Goodman DM. Early postoperative fluid overload precedes acute kidney injury and is associated with higher morbidity in pediatric cardiac surgery patients. Pediatr Crit Care Med. 2014 Feb;15(2):131-8. doi: 10.1097/PCC.0000000000000043.
- Magee G, Zbrozek A. Fluid overload is associated with increases in length of stay and hospital costs: pooled analysis of data from more than 600 US hospitals. Clinicoecon Outcomes Res. 2013 Jun 26;5:289-96. doi: 10.2147/CEOR.S45873. Print 2013.
- Vaara ST, Korhonen AM, Kaukonen KM, Nisula S, Inkinen O, Hoppu S, Laurila JJ, Mildh L, Reinikainen M, Lund V, Parviainen I, Pettila V; FINNAKI Study Group. Fluid overload is associated with an increased risk for 90-day mortality in critically ill patients with renal replacement therapy: data from the prospective FINNAKI study. Crit Care. 2012 Oct 17;16(5):R197. doi: 10.1186/cc11682.
- Di Lullo L, Gorini A, Russo D, Santoboni A, Ronco C. Left Ventricular Hypertrophy in Chronic Kidney Disease Patients: From Pathophysiology to Treatment. Cardiorenal Med. 2015 Oct;5(4):254-66. doi: 10.1159/000435838. Epub 2015 Jul 15.
- Ekinci C, Karabork M, Siriopol D, Dincer N, Covic A, Kanbay M. Effects of Volume Overload and Current Techniques for the Assessment of Fluid Status in Patients with Renal Disease. Blood Purif. 2018;46(1):34-47. doi: 10.1159/000487702. Epub 2018 Apr 12.
- Collins AJ, Foley RN, Gilbertson DT, Chen SC. United States Renal Data System public health surveillance of chronic kidney disease and end-stage renal disease. Kidney Int Suppl (2011). 2015 Jun;5(1):2-7. doi: 10.1038/kisup.2015.2.
- Chang ST, Chen CL, Chen CC, Lin FC, Wu D. Enhancement of quality of life with adjustment of dry weight by echocardiographic measurement of inferior vena cava diameter in patients undergoing chronic hemodialysis. Nephron Clin Pract. 2004;97(3):c90-7. doi: 10.1159/000078636.
- Andreucci M, Russo D, Fuiano G, Minutolo R, Andreucci VE. Diuretics in renal failure. Miner Electrolyte Metab. 1999 Jan-Apr;25(1-2):32-8. doi: 10.1159/000057416.
- Wilcox CS. New insights into diuretic use in patients with chronic renal disease. J Am Soc Nephrol. 2002 Mar;13(3):798-805. doi: 10.1681/ASN.V133798.
- Roberts MA. Commentary on the KDIGO Clinical Practice Guideline for the management of blood pressure in chronic kidney disease. Nephrology (Carlton). 2014 Jan;19(1):53-5. doi: 10.1111/nep.12168. No abstract available.
- Hoorn EJ, Ellison DH. Diuretic Resistance. Am J Kidney Dis. 2017 Jan;69(1):136-142. doi: 10.1053/j.ajkd.2016.08.027. Epub 2016 Nov 1.
- Bowman BN, Nawarskas JJ, Anderson JR. Treating Diuretic Resistance: An Overview. Cardiol Rev. 2016 Sep-Oct;24(5):256-60. doi: 10.1097/CRD.0000000000000116.
- Knepper MA. Systems biology of diuretic resistance. J Clin Invest. 2015 May;125(5):1793-5. doi: 10.1172/JCI81505. Epub 2015 Apr 20.
- Shahin MH, Johnson JA. Mechanisms and pharmacogenetic signals underlying thiazide diuretics blood pressure response. Curr Opin Pharmacol. 2016 Apr;27:31-7. doi: 10.1016/j.coph.2016.01.005. Epub 2016 Feb 10.
- Yugar LBT, Moreno B, Moreno H, Vilela-Martin JF, Yugar-Toledo JC. Do thiazide diuretics reduce central systolic blood pressure in hypertension? J Clin Hypertens (Greenwich). 2018 Jan;20(1):133-135. doi: 10.1111/jch.13134. Epub 2017 Nov 6. No abstract available.
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- Dargie HJ, Allison ME, Kennedy AC, Gray MJ. High dosage metolazone in chronic renal failure. Br Med J. 1972 Oct 28;4(5834):196-8. doi: 10.1136/bmj.4.5834.196.
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- Fliser D, Schroter M, Neubeck M, Ritz E. Coadministration of thiazides increases the efficacy of loop diuretics even in patients with advanced renal failure. Kidney Int. 1994 Aug;46(2):482-8. doi: 10.1038/ki.1994.298.
- Knauf H, Mutschler E. Diuretic effectiveness of hydrochlorothiazide and furosemide alone and in combination in chronic renal failure. J Cardiovasc Pharmacol. 1995 Sep;26(3):394-400. doi: 10.1097/00005344-199509000-00008.
- Dussol B, Moussi-Frances J, Morange S, Somma-Delpero C, Mundler O, Berland Y. A randomized trial of furosemide vs hydrochlorothiazide in patients with chronic renal failure and hypertension. Nephrol Dial Transplant. 2005 Feb;20(2):349-53. doi: 10.1093/ndt/gfh650. Epub 2004 Dec 22.
- Dussol B, Moussi-Frances J, Morange S, Somma-Delpero C, Mundler O, Berland Y. A pilot study comparing furosemide and hydrochlorothiazide in patients with hypertension and stage 4 or 5 chronic kidney disease. J Clin Hypertens (Greenwich). 2012 Jan;14(1):32-7. doi: 10.1111/j.1751-7176.2011.00564.x. Epub 2011 Dec 9.
- Agarwal R, Sinha AD, Pappas MK, Ammous F. Chlorthalidone for poorly controlled hypertension in chronic kidney disease: an interventional pilot study. Am J Nephrol. 2014;39(2):171-82. doi: 10.1159/000358603. Epub 2014 Feb 11.
- Cirillo M, Marcarelli F, Mele AA, Romano M, Lombardi C, Bilancio G. Parallel-group 8-week study on chlorthalidone effects in hypertensives with low kidney function. Hypertension. 2014 Apr;63(4):692-7. doi: 10.1161/HYPERTENSIONAHA.113.02793. Epub 2014 Jan 6.
- Solis-Jimenez F, Perez-Navarro LM, Cabrera-Barron R, Chida-Romero JA, Martin-Alemany G, Dehesa-Lopez E, Madero M, Valdez-Ortiz R. Effect of the combination of bumetanide plus chlorthalidone on hypertension and volume overload in patients with chronic kidney disease stage 4-5 KDIGO without renal replacement therapy: a double-blind randomized HEBE-CKD trial. BMC Nephrol. 2022 Sep 20;23(1):316. doi: 10.1186/s12882-022-02930-4.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2019年6月18日
初级完成 (实际的)
2019年10月28日
研究完成 (实际的)
2019年10月28日
研究注册日期
首次提交
2019年4月18日
首先提交符合 QC 标准的
2019年4月22日
首次发布 (实际的)
2019年4月23日
研究记录更新
最后更新发布 (实际的)
2020年11月23日
上次提交的符合 QC 标准的更新
2020年11月4日
最后验证
2020年11月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.