The Efficacy and Safety of Guilu Erxian Jiao in the Treatment of Intradialytic Hypotension

NCT ID: NCT06980922

Last Updated: 2025-05-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

34 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-06-01

Study Completion Date

2028-05-31

Brief Summary

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The goal of this clinical trial is to learn if Guilu Erxian Jiao, a traditional Chinese herbal medicine, can help manage intradialytic hypotension (IDH), a drop in blood pressure that occurs during hemodialysis in adults. The main questions it aims to answer are:

1. Does Guilu Erxian Jiao reduce the frequency and severity of low blood pressure during dialysis?
2. Is Guilu Erxian Jiao safe to use in patients receiving hemodialysis?

Researchers will compare standard care plus Guilu ErXian Jiao to standard care alone to see if Guilu Erxian Jiao improves blood pressure stability during dialysis.

Participants will:

1. Take Guilu Erxian Jiao once daily in addition to standard care, or receive standard care alone, for 4 weeks, then switch treatments after a 4-week washout period (crossover design).
2. Undergo follow-up assessments at weeks 2 and 4 after each treatment phase.
3. Have their blood pressure monitored before, during (hourly), and after each dialysis session.
4. Report dialysis-related symptoms such as dizziness and fatigue.
5. Receive routine laboratory tests and safety monitoring throughout the study.

Detailed Description

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1. Clinical Background and Study Rationale

Intradialytic hypotension (IDH) is defined as a decrease in systolic blood pressure of more than 20 mmHg or a drop of more than 10 mmHg in mean arterial pressure during hemodialysis, often accompanied by symptoms such as dizziness, nausea, or cramps. The incidence of IDH among dialysis patients is approximately 5% to 30%. Risk factors include advanced age, diabetes, female sex, and high body mass index. IDH can cause premature termination of dialysis sessions, resulting in decreased uremic toxin clearance and increased long-term mortality and complications. Severe IDH may lead to bowel ischemia, stroke, or myocardial infarction.

Common management strategies for IDH include adjusting the dialysis rate, lowering dialysate temperature, avoiding eating during dialysis, and strict sodium intake control. In cases of frequent IDH episodes, drugs such as Midodrine or Vasopressin may be used. However, oral Midodrine can cause side effects such as urinary retention, paresthesia, and pruritus. Its long-term safety in dialysis patients is yet to be confirmed.

According to Traditional Chinese Medicine (TCM), IDH results from spleen and kidney Qi deficiency, requiring tonification of these organs. Guilu Erxian Jiao (GLJ) is a classical formula composed of Testudinis Carapax, Cervi Cornu, Lycii Fructus, and Ginseng Radix, commonly used to treat Qi deficiency and hypotension. Clinical experience suggests potential efficacy in reducing IDH frequency, but large-scale trials are lacking.

This trial aims to evaluate the efficacy and safety of GLJ in treating IDH in patients undergoing hemodialysis.
2. Study Design and Methods

This is a randomized, open-label, crossover clinical trial enrolling 34 patients aged over 18 years who receive thrice-weekly hemodialysis for four hours per session and have a history of IDH. Patients are recruited from nephrology and TCM outpatient clinics and the dialysis unit of Keelung Chang Gung Memorial Hospital.

Participants will be randomized 1:1 into two groups. Randomization will be performed using a computer-generated random sequence. Participants will be assigned to groups according to sealed envelopes that indicate their allocation. Group A receives GLJ plus conventional treatment for four weeks, followed by a four-week washout period, then four weeks of conventional treatment alone. Group B follows the reverse sequence.

GLJ (Guilu Erxian Jiao) is administered once daily before meals at a dose of 4 grams for four weeks. The preparation used is Jipin Guilu Baishen San produced by Sun Ten Pharmaceutical Co., Ltd. (License number: 016966).

Data collected include demographic information, medical history, allergy history, family history, medication history, and socioeconomic status. Evaluations include blood pressure measurements before, during, and after dialysis; frequency of IDH episodes; symptoms such as dizziness and fatigue (via VAS score); laboratory parameters (Na, K, Ca, P, BUN, Cr); and adverse events.

Follow-up evaluations occur at weeks 2 and 4 after each treatment phase. Each assessment takes approximately 30 minutes.
3. Participant Safety, Compensation, and Withdrawal Rights

Guilu Erxian Jiao is generally well tolerated. Reported side effects in prior studies include mild dry mouth and constipation. During the study, blood and biochemical parameters will be regularly monitored to detect any possible adverse effects.

If allergic reactions or serious adverse events occur during the trial, the participant will be withdrawn from the study and provided with appropriate medical evaluation and care.

Participants may voluntarily withdraw from the study at any time without providing a reason and without any impact on their standard medical care. Likewise, the principal investigator reserves the right to terminate a participant's involvement or discontinue the trial at any time for safety or administrative reasons.

In case of adverse events or injuries resulting from participation in this study, and if they occur in accordance with the approved protocol, the institution and the principal investigator will be legally responsible for providing necessary compensation. However, no compensation will be provided for anticipated side effects explicitly stated in the study protocol. In addition to compensation, the hospital will also provide professional medical care and consultation at no cost for treating the injury.
4. Data Privacy and Confidentiality

Participant identities will be anonymized using unique study codes, and no personally identifiable information (e.g., name, medical record number) will appear in the case reports or publications. Study data will be securely stored in locked cabinets and password-protected, encrypted folders for at least two years after the end of the study. Only the principal investigator, authorized research team members, auditors, the ethics committee, and regulatory authorities will have access to the original data for monitoring and auditing purposes. The research team is committed to maintaining confidentiality and protecting participants' privacy throughout the study.
5. Statistical Analysis

Sample size calculation was based on previous studies with a significance level of 0.05 and power of 0.99, resulting in a required 28 participants; with an estimated 20% dropout rate, 34 participants will be enrolled.

Statistical analyses include Student's t-test, Chi-square test, ANOVA, and paired t-tests as appropriate. Non-parametric tests will be used if data are not normally distributed. All efficacy analyses will be performed using the intention-to-treat (ITT) principle, including all randomized participants who received at least one dose of study intervention. A one-sided alpha of 0.05 defines statistical significance.
6. IRB Review and Approval This study has been reviewed and approved by the Institutional Review Board of Chang Gung Memorial Hospital, Keelung Branch (IRB No. 2402010026, Protocol Version 5, approved on 2025/03/12).

Conditions

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Intradialytic Hypotension End-Stage Renal Disease Hemodialysis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

This is a two-period, two-sequence crossover trial with a 4-week treatment phase and a 4-week washout period. Participants are randomized in a 1:1 ratio to receive either Guilu Erxian Jiao plus usual care followed by usual care alone, or the reverse sequence.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Group A

Participants in Group A will receive Guilu Erxian Jiao (GLJ) plus usual care for 4 weeks, followed by a 4-week washout period, then 4 weeks of usual care alone.

Group Type EXPERIMENTAL

Guilu Erxian Jiao

Intervention Type DRUG

A traditional Chinese herbal formula composed of Testudinis Carapax, Cervi Cornu, Lycii Fructus, and Ginseng Radix, manufactured by Sun Ten Pharmaceutical Co., Ltd. (License No. 016966). Administered orally at 4 grams per day before meals for 4 weeks.

Group B

Participants in Group B will receive usual care alone for 4 weeks, followed by a 4-week washout period, then 4 weeks of Guilu Erxian Jiao (GLJ) plus usual care.

Group Type ACTIVE_COMPARATOR

Guilu Erxian Jiao

Intervention Type DRUG

A traditional Chinese herbal formula composed of Testudinis Carapax, Cervi Cornu, Lycii Fructus, and Ginseng Radix, manufactured by Sun Ten Pharmaceutical Co., Ltd. (License No. 016966). Administered orally at 4 grams per day before meals for 4 weeks.

Interventions

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Guilu Erxian Jiao

A traditional Chinese herbal formula composed of Testudinis Carapax, Cervi Cornu, Lycii Fructus, and Ginseng Radix, manufactured by Sun Ten Pharmaceutical Co., Ltd. (License No. 016966). Administered orally at 4 grams per day before meals for 4 weeks.

Intervention Type DRUG

Other Intervention Names

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Jipin Guilu Baishen San

Eligibility Criteria

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Inclusion Criteria

* Age ≥ 18 years
* Undergoing maintenance hemodialysis three times per week, 4 hours per session
* History of intradialytic hypotension (IDH)
* Willing and able to provide written informed consent

Exclusion Criteria

* Pregnant or lactating women
* Severe comorbid illness, such as cancer, stroke, or liver cirrhosis
* Inability to comply with study medication regimen
* Regular use of antihypertensive medication
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Chang Gung Memorial Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Huan-Hsuan Hsu, M.D.

Role: PRINCIPAL_INVESTIGATOR

Department of Chinese Medicine, Keelung Chang Gung Memorial Hospital

Locations

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Keelung Chang Gung Memorial Hospital

Keelung, , Taiwan

Site Status

Countries

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Taiwan

Central Contacts

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Huan-Hsuan Hsu, M.D.

Role: CONTACT

+886-2-24313131 ext. 2677

Chun-Jung Lin, M.D.

Role: CONTACT

+886-2-24313131 ext. 2677

Facility Contacts

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Huan-Hsuan Hsu, M.D.

Role: primary

+886-2-24313131 ext. 2677

Chun-Jung Lin, M.D.

Role: backup

+886-2-24313131 ext. 2677

References

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Brunelli SM, Cohen DE, Marlowe G, Van Wyck D. The Impact of Midodrine on Outcomes in Patients with Intradialytic Hypotension. Am J Nephrol. 2018;48(5):381-388. doi: 10.1159/000494806. Epub 2018 Nov 13.

Reference Type BACKGROUND
PMID: 30423552 (View on PubMed)

Jindal K, Chan CT, Deziel C, Hirsch D, Soroka SD, Tonelli M, Culleton BF; Canadian Society of Nephrology Committee for Clinical Practice Guidelines. Hemodialysis clinical practice guidelines for the Canadian Society of Nephrology. J Am Soc Nephrol. 2006 Mar;17(3 Suppl 1):S1-27. doi: 10.1681/ASN.2005121372. No abstract available.

Reference Type BACKGROUND
PMID: 16497879 (View on PubMed)

Flythe JE, Xue H, Lynch KE, Curhan GC, Brunelli SM. Association of mortality risk with various definitions of intradialytic hypotension. J Am Soc Nephrol. 2015 Mar;26(3):724-34. doi: 10.1681/ASN.2014020222. Epub 2014 Sep 30.

Reference Type BACKGROUND
PMID: 25270068 (View on PubMed)

Morfin JA, Fluck RJ, Weinhandl ED, Kansal S, McCullough PA, Komenda P. Intensive Hemodialysis and Treatment Complications and Tolerability. Am J Kidney Dis. 2016 Nov;68(5S1):S43-S50. doi: 10.1053/j.ajkd.2016.05.021.

Reference Type BACKGROUND
PMID: 27772642 (View on PubMed)

Flythe JE, Inrig JK, Shafi T, Chang TI, Cape K, Dinesh K, Kunaparaju S, Brunelli SM. Association of intradialytic blood pressure variability with increased all-cause and cardiovascular mortality in patients treated with long-term hemodialysis. Am J Kidney Dis. 2013 Jun;61(6):966-74. doi: 10.1053/j.ajkd.2012.12.023. Epub 2013 Mar 6.

Reference Type BACKGROUND
PMID: 23474007 (View on PubMed)

Tattersall J, Martin-Malo A, Pedrini L, Basci A, Canaud B, Fouque D, Haage P, Konner K, Kooman J, Pizzarelli F, Tordoir J, Vennegoor M, Wanner C, ter Wee P, Vanholder R. EBPG guideline on dialysis strategies. Nephrol Dial Transplant. 2007 May;22 Suppl 2:ii5-21. doi: 10.1093/ndt/gfm022. No abstract available.

Reference Type BACKGROUND
PMID: 17507427 (View on PubMed)

Mo Y, Liu X, Qin X, Huang J, He Z, Lin J, Hu Q, Cai Y, Liu Z, Wang L. Shenfu injection for intradialytic hypotension: a systematic review and meta-analysis. Evid Based Complement Alternat Med. 2014;2014:279853. doi: 10.1155/2014/279853. Epub 2014 Dec 22.

Reference Type BACKGROUND
PMID: 25587340 (View on PubMed)

Sands JJ, Usvyat LA, Sullivan T, Segal JH, Zabetakis P, Kotanko P, Maddux FW, Diaz-Buxo JA. Intradialytic hypotension: frequency, sources of variation and correlation with clinical outcome. Hemodial Int. 2014 Apr;18(2):415-22. doi: 10.1111/hdi.12138. Epub 2014 Jan 27.

Reference Type BACKGROUND
PMID: 24467830 (View on PubMed)

Kooman J, Basci A, Pizzarelli F, Canaud B, Haage P, Fouque D, Konner K, Martin-Malo A, Pedrini L, Tattersall J, Tordoir J, Vennegoor M, Wanner C, ter Wee P, Vanholder R. EBPG guideline on haemodynamic instability. Nephrol Dial Transplant. 2007 May;22 Suppl 2:ii22-44. doi: 10.1093/ndt/gfm019. No abstract available.

Reference Type BACKGROUND
PMID: 17507425 (View on PubMed)

Other Identifiers

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202400179A3C601

Identifier Type: -

Identifier Source: org_study_id

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