Please select the eligibility criteria that correspond to the clinical trial below.
Title: N/A
Brief Summary: Uraemic pruritus (UP) remains a frequent and distressing problem in patients with advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD).

Calmmax is a new topical cream that was introduced recently by Calmmax Pharma, an Israeli pharmaceutical company developed a topical cream based on active plant extracts for treatment of skin inflammation. We intend to conduct a prospective, double blind, placebo controlled, randomized trial that will assess the therapeutic effect of Calmmax cream on UP in a cohort of CKD and ESRD patients.


Options:
A: Inclusion Criteria:

* Hemodialysis patients
* Suffering from pruritus for at least 6 weeks
* Have not responded to other drugs

Exclusion Criteria:

* Dermatological disease
* Liver disease
* Metabolic disease
B: Inclusion Criteria:

* On stable hemodialysis for at least 3 months
* Has stable functioning arteriovenous fistula, graft or other venous access
* Has continued (uncontrolled) uremic pruritus despite standard of care in the institution
* Has severe pruritus, as determined by a qualifying score of ≥3 on the Itch Severity Score Scale (0 to 4) either day or night during the week prior to Screening Visit
* Has no known drug addiction to any prescription, nonprescription, herbal or natural drugs, and successfully passes a drug screen test
* Women and men whose partners are of childbearing potential agree to practice the medically acceptable methods of birth control and agree to continue with the regimen throughout the duration of the study
* Capable of understanding and responding to the subject questionnaires, understands the purpose and risks of the study, and has given written informed consent
* Has rated his/her NRS score each day for at least 5 days out of the 7 days of the Run-in Phase
* Has severe pruritus, as determined by qualifying mean worst NRS score in a day of ≥5 (on 11 point NRS) at the end of the 1-week Run-in Phase

Exclusion Criteria:

* Current, clinically significant medical comorbidities
* Abnormal liver dysfunction
* Pruritus attributed mainly to any disease unrelated to kidney disease
* Calcium x phosphorus product \>80 mg2/dL2 or hemoglobin \<7 g/dL or parathyroid hormone levels \>1000 pg/mL at Screening
* Received ultraviolet B treatment within 30 days prior to Screening
* Started or changed psychotropic medication within 14 days prior to Screening
* Is receiving opioid antagonists or opioid agonists within 7 days prior to Screening and not willing to abstain from these medications during the study.
* Started or changed medications, creams or emollients including over-the-counter oil bath treatment for relief of pruritus within 7 days prior to Screening
* Has known hypersensitivity to opioids or the study drug ingredients
* Is currently participating in an investigational drug or device clinical study or was participating in such a study within 30 days prior to the start of Screening
* Female subject who is known to be pregnant or nursing
* Is considered not suitable for inclusion in the study in the opinion of Investigator
* Has current suicidal ideation with some intent to act or with specific plan and intent or had suicidal behavior at any time in subject's life
C: Inclusion Criteria:

* Willingness to sign an informed consent
* Stable haemodialysis treatment for more than 3 months, undergoing 2 to 3 times haemodialysis a week for 4 to 5 hours per session
* middle or large molecules retention defined as immunoreactive parathyroid hormone (iPTH) \> 400 pg/mL, β2MG\>5000 pg/ml、CRP\>10mg/l.
* Refractory pruritus, carpal tunnel syndrome, restless leg syndrome, hyperparathyroidism or other refratory complications.

Exclusion Criteria:

* Incapable or reluctant to sign the informed consent or comply the schedule.
* platelet (PLT) count\<60×109/L or disturbance in coagulation, tendency of severe bleeding or acute bleeding.
* Severe hypotension and heart or lung insufficiency
* Known hypersensitive or contradiction or intolerance to dialyzer or adsorbents
* Attend to other clinic trial now or in recent 30 days
D: Inclusion Criteria:

1. History of pruritus of \>8 weeks duration.
2. Severity score of pruritus ≥5 as defined by VAS
3. Discontinuation of any medication with presumed antipruritic effects at least 1 week before the study (including Calmmax cream)
4. Negative pregnancy test result for all participating women of childbearing age;

Exclusion Criteria:

1. Known allergy to Calmmax cream
2. Any acute illness
3. Liver cirrhosis
4. Active dermatological disorder other than UP
5. Decompensated heart failure
6. Inability to give informed consent
7. Known poor adherence to medical recommendations

Answer: D