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Trial registered on ANZCTR


Registration number
ACTRN12623000980639
Ethics application status
Approved
Date submitted
3/08/2023
Date registered
8/09/2023
Date last updated
8/09/2023
Date data sharing statement initially provided
8/09/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of Angiotensin II in Cramp Reduction for Maintenance Patients on HaemoDialysis
Scientific title
Efficacy of Angiotensin II in Cramp Reduction for Kidney Failure Patients on Maintenance HaemoDialysis
Secondary ID [1] 310288 0
Nil known
Universal Trial Number (UTN)
Trial acronym
CRAMP HD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Painful muscle cramps
 330985 0
Condition category
Condition code
Musculoskeletal 327803 327803 0 0
Other muscular and skeletal disorders
Renal and Urogenital 327959 327959 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Infusion of 2.5mg angiotensin II in 500mL normal saline (concentration 5000 ng/mL) titrated between 0.1 and 30 ng/kg/min and administered during the first haemodialysis session of the week for two of four weeks. The remaining two haemodialysis treatments will function as the 'wash out' period.
Intervention code [1] 326672 0
Treatment: Drugs
Comparator / control treatment
Infusion of 500mL normal saline titrated at equivalent rate in mL/hour as intervention infusion (i.e. exact rate weight-dependent) and administered during the first haemodialysis session of the week for two of four weeks. The remaining two haemodialysis treatments will function as the 'wash out' period.
Control group
Placebo

Outcomes
Primary outcome [1] 335651 0
Safety (composite of systolic blood pressure greater than 180 mmHg requiring intervention, arteriovenous fistula or graft thrombosis, venous thromboembolic event, arterial thromboembolic event) as identified from patient medical records.
Timepoint [1] 335651 0
28 days (i.e. end of 4 dialysis treatment weeks during both intervention and placebo periods)
Secondary outcome [1] 425082 0
Intradialytic hypotension (decrease in systolic blood pressure of 20 mmHg or systolic blood pressure less than 90 mmHg associated with symptoms) as measured using a non-invasive blood pressure monitor (Edwards ClearSight)
Timepoint [1] 425082 0
During the first dialysis session each week over 4 consecutive weeks during both intervention and placebo periods
Secondary outcome [2] 425084 0
Painful muscle cramp as assessed using the Brief Pain Inventory
Timepoint [2] 425084 0
During the first dialysis session each week over 4 consecutive weeks during both intervention and placebo periods
Secondary outcome [3] 425085 0
Intradialytic symptoms (abdominal pain, nausea, vomiting, restlessness, dizziness, fainting, “going flat”) as reported by patients via the case report form
Timepoint [3] 425085 0
During the first dialysis session each week over 4 consecutive weeks during both intervention and placebo periods
Secondary outcome [4] 425086 0
Change in serum renin level from baseline
Timepoint [4] 425086 0
Baseline (pre-dialysis) and end of dialysis session (measured in the first dialysis session each week over 4 consecutive weeks during both intervention and placebo periods)
Secondary outcome [5] 425088 0
Change in serum catecholamine level from baseline
Timepoint [5] 425088 0
Baseline (pre-dialysis) and end of dialysis session (measured in the first dialysis session each week over 4 consecutive weeks during both intervention and placebo periods)
Secondary outcome [6] 425091 0
Change in serum troponin level from baseline
Timepoint [6] 425091 0
Baseline (pre-dialysis) and end of dialysis session (measured in the first dialysis session each week over 4 consecutive weeks during both intervention and placebo periods)
Secondary outcome [7] 425092 0
Change in serum creatine kinase level from baseline
Timepoint [7] 425092 0
Baseline (pre-dialysis) and end of dialysis session (measured in the first dialysis session each week over 4 consecutive weeks during both intervention and placebo periods)
Secondary outcome [8] 425094 0
Haemodialysis treatment alteration due to cramps (fluid bolus administration, reduction in ultrafiltration goal, treatment termination, reduction in dialyser blood flow rate) as identified from patient medical records
Timepoint [8] 425094 0
During the first dialysis session each week over 4 consecutive weeks during both intervention and placebo periods
Secondary outcome [9] 425095 0
Haemodialysis treatment alteration for reasons other than cramps (fluid bolus administration, reduction in ultrafiltration goal, treatment termination, reduction in dialyser blood flow rate) as identified from the patient medical record
Timepoint [9] 425095 0
During the first dialysis session each week over 4 consecutive weeks during both intervention and placebo periods
Secondary outcome [10] 425096 0
Target weight achievement as identified using digital scales
Timepoint [10] 425096 0
During the first dialysis session each week over 4 consecutive weeks during both intervention and placebo periods

Eligibility
Key inclusion criteria
1. Adults aged at least 18 years
2. Chronic haemodialysis for kidney failure (i.e. 3 times per week)
3. Recent history of painful muscle cramps defined by:
3.1 Early termination of a dialysis session due to muscle cramps in the previous month
3.2 Reduction in prescribed ultrafiltration or administration of fluid due to muscle cramps in the previous month
4. Arteriovenous fistula, graft or permacath in situ
5. Informed consent provided by the patient or medical treatment decision maker
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known or suspected allergy to components of angiotensin II
2. Presently taking an angiotensin II receptor blocker
3. Previous intra-cerebral haemorrhage
4. Pre-dialysis hypertension (SBP >180 mmHg)
5. Severe heart failure (LVEF <20%)
6. Any other disease or clinically significant abnormality in laboratory parameters that, according to the investigator, might compromise the safety of the subject or interfere with participation in the trial or compromise the trial objective

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using computerised sequence generation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Baseline characteristics will be expressed as numbers and percentages, means and standard deviations, or medians and interquartile ranges, as appropriate. Group comparisons will be made by t-test, chi-square test, and Wilcoxon rank sum test, as dictated by data type.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/10/2023
Actual
Date of last participant enrolment
Anticipated
31/01/2024
Actual
Date of last data collection
Anticipated
29/02/2024
Actual
Sample size
Target
16
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 25320 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 25321 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 41025 0
3050 - Parkville
Recruitment postcode(s) [2] 41024 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 314500 0
Hospital
Name [1] 314500 0
Austin Health
Country [1] 314500 0
Australia
Primary sponsor type
Individual
Name
Rinaldo Bellomo
Address
Austin Health
Burgundy St
Heidelberg VIC 3084
Country
Australia
Secondary sponsor category [1] 316445 0
None
Name [1] 316445 0
Address [1] 316445 0
Country [1] 316445 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313545 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 313545 0
145 Studley Road
Heidelberg VIC 3084
Ethics committee country [1] 313545 0
Australia
Date submitted for ethics approval [1] 313545 0
Approval date [1] 313545 0
25/07/2023
Ethics approval number [1] 313545 0

Summary
Brief summary
Skeletal muscle cramping is a common and bothersome symptom for patients on maintenance dialysis therapy. Although initially considered to be an intradialytic phenomenon associated with rapid fluid removal during haemodialysis, accumulating evidence indicates that dysfunction of the renin-angiotensin-aldosterone system (RAAS) may play a significant role in its pathophysiology. This is a multicentre, phase 2, placebo-controlled, randomised crossover trial of the safety, tolerability, and efficacy of angiotensin II in chronic haemodialysis patients who regularly experience cramps. We hypothesise that angiotensin II will be safe, feasible, and effective at reducing cramping.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 128498 0
Prof Rinaldo Bellomo
Address 128498 0
Austin Health145 Studley Road Heidelberg VIC 3084
Country 128498 0
Australia
Phone 128498 0
+61 3 9496 4835
Fax 128498 0
Email 128498 0
rinaldo.bellomo@austin.org.au
Contact person for public queries
Name 128499 0
Dr Emily See
Address 128499 0
Austin Health145 Studley RoadHeidelberg VIC 3084
Country 128499 0
Australia
Phone 128499 0
+61 3 9496 4835
Fax 128499 0
Email 128499 0
emily.see@austin.org.au
Contact person for scientific queries
Name 128500 0
Dr Emily See
Address 128500 0
Austin Health145 Studley RoadHeidelberg VIC 3084
Country 128500 0
Australia
Phone 128500 0
+61 3 9496 4835
Fax 128500 0
Email 128500 0
emily.see@mh.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
19893Study protocol  emily.see@austin.org.au



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically
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