Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multicenter, Double-blind, Randomized, Placebo and Active-controlled Study of Pregabalin for the Treatment of Uremic Pruritus
Brief Summary: Pruritus s a very distressing problem affecting patients with uremia and the prevalence of uremic pruritus (UP) ranges between 22% to 66%. Although some studies suggested pruritus is being decreased recently by use of better dialysis techniques, accumulating studies have shown the still high prevalence of UP. Because of its long duration, frequency and high intensity, UP has been reported to have a negative impact upon the patients' quality of life (QoL). However, the therapies in use, including antihistamines, ultraviolets, opioid antagonists and topical agents, are generally of insufficient efficacy, failing to provide adequate and long-lasting relief. Based on the neuropathic hypothesis and frequent co-occurrence of chronic pruritus and peripheral neuropathy in the patients undergoing hemodialysis, gabapentin, a medication widely used for a spectrum of neuropathic pain syndromes, has recently been suggested to be effective in the treatment of UP.Pregabalin, another gabaergic drug structurally related to gabapentin, have an advantage over gabapentin in terms of its more rapid response to stressful symptoms. Only two very recently small-scaled studies evaluate the effect of pregabalin for UP. However, both these studies were not randomized, placebo-controlled trails.As UP is still one of the most vexing and disabling symptoms in patients with ESRD, we decided to do this multicenter, randomized double-blind placebo-controlled trial (RCT) with a larger sample size and a longer duration.


Options:
A: Inclusion Criteria:

1. Willing and able to provide written informed consent prior to participating in this study;
2. Able to communicate clearly with the Investigator and staff, able to read, complete questionnaires, and understand the study procedures;
3. Males or females 18 years of age or older;
4. ESRD patients who have been on hemodialysis 3 times per week for at least 3 months prior to the start of Screening;
5. Women of child-bearing potential must have a negative serum pregnancy test and agree to practice an acceptable form of birth control for the duration of the study
6. Male patients that are not biologically or surgically sterile must agree to practice an acceptable from of birth control for the duration of the study
7. Weigh between 88.2 lb (40.0 kg) and 297.6 lb (135.0 kg).
8. Patient must self-report pruritus in the month prior to screening.
9. If patient is receiving treatment for itch, this treatment must be stable prior to screening and during treatment period.
10. At least 2 single-pool Kt/V measurements ≥ 1.2, or at least 2 urea reduction ratio measurements ≥ 65%, or 1 single-pool Kt/V measurement ≥ 1.2 and 1 urea reduction ratio measurement ≥ 65% on different dialysis days during the 3 months period prior to Screening;
11. Patient who self-categorize as moderate-to-severe itch.

Exclusion Criteria:

1. Known to be non-compliant with dialysis treatment (i.e., has missed more than 2 dialysis sessions in the past 2 months because of non-compliance);
2. Anticipated to receive a kidney transplant during the study;
3. Known history of allergic reaction to opiates, such as hives
4. Known or suspected history of alcohol, narcotic, or other drug abuse or dependence within 12 months prior to Screening;
5. Patient has any clinically relevant acute or chronic medical or neuropsychiatric condition which, in the opinion of the Investigator, would pose undue risk to the patient, would impede completion of the study procedures, or would compromise the validity of the study measurements;
6. Serum alanine aminotransferase or aspartate aminotransferase greater than 2.5 times the reference upper limit of normal (ULN), or total bilirubin greater than 2 times ULN at Screening;
7. Received another investigational drug within 30 days prior to the start of Screening or has planned to participate in another clinical trial while enrolled in this study;
8. Has pruritus probably or definitely attributed to a cause other than ESRD or its complications (e.g., patients with concomitant pruritic dermatological disease or cholestatic liver disease would be excluded). (Note: Patients whose pruritus is attributed to ESRD complications such as hyperparathyroidism, hyperphosphatemia, anemia, or the dialysis procedure or prescription may be enrolled);
9. Has localized itch restricted to the palms of the hands;
10. Has pruritus only during the dialysis session (by patient report);
11. Anticipated to receive opioid antagonists (e.g., naloxone, naltrexone), or opioid mixed agonist-antagonist (e.g., buprenorphine, nalbuphine) from the start of Screening through the end of the Treatment Period;
12. Used Salvia divinorum or Salvinorin A within 30 days prior to the start of Screening or is anticipated to use it during the study;
13. Received ultraviolet B treatment within 30 days prior to the start of Screening or anticipated to receive such treatment during the study;
14. Participated in a previous clinical trial with CR845.
B: Inclusion Criteria:

* Adult Chinese male and female patients aged \> 18 undergoing CAPD for at least 3 months and able to read and understand Chinese
* Patients experiencing moderate to severe pruritis, defined as persistent, treatment-resistant pruritis considerably impairing sleep or daytime activity. Treatment resistance is defined as no or only partial resolvement of pruritis under current anti-pruritis treatment regimens such as anti-pruritis lotions and anti-histamines.
* Patients in stable clinical condition in terms of peritoneal dialysis and general health
* Patients able to understand and answer the SDS questionnaire
* Patients able to express the sensation of itchiness in the terms of the VAS and the SDS score
* Patients who are willing to give written informed consent and to participate in and comply with the study protocol

Exclusion Criteria:

* Patients with a known history of pruritis or dermatologic disease antedating renal failure.
* Patients with skin disease other than the usual cutaneous findings of uraemia such as xerosis or ecchymosis.
* Patients under current treatment with systemic steroids
* Known history of allergy to Gabapentin
* Those patients already put on anti-convulsants
* Unable to give written informed consent for the study
* Pregnancy or female patients of child-bearing age who are unwilling to use contraception
* Poor drug compliance
* Known HIV positivity
* Active neoplastic disease
* Those who do not want to participate the study
C: Inclusion Criteria:

1. History of pruritus of \>8 weeks duration.
2. Severity of pruritus of 7 or more defined by visual analogue scale.
3. No improvement by oral antihistamines or skin moisturizers.
4. Discontinuation of any medication with presumed antipruritic effects at least 1 week before the study.
5. Negative pregnancy test result for all participating women of childbearing age;

Exclusion Criteria:

1. Known allergy to Pregabalin
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. Poor compliance.
D: Inclusion Criteria:

* Patients who have end-stage renal disease (ESRD) on maintenance hemodialysis more than twice weekly for at least three months and suffered from uremic pruritus.
* 20 Years and older
* Definition of uremic pruritus:

Patients were considered to have pruritus if they had either of the following conditions:

* at least 3 episodes of itch during a period of 2 weeks or less, with the symptom appearing a few times a day, lasting at least a few minutes, and troubling the patient
* he appearance of an itch in a regular pattern during a period of 6 months, but less frequently than listed above.

To be defined as "uremic," the pruritus had to appear shortly before the onset of dialysis, or at any time after that, without evidence of any other active disease that could explain the pruritus.

-Patients who suffer from severe pruritus unresponsive to topical emollient and corticosteroids, and were diagnosed as having uremic pruritus by dermatologists

Exclusion Criteria:

1. All patients with pruritus attributable to any other causes, such as scabies or other evident skin diseases (atopic dermatitis, psoriasis, generalized dermatitis, pediculosis, urticaria ...etc), and any medication with potential pruritic properties.
2. Patients whose pruritus occurred only during dialysis
3. Patients received oral drugs with presumed antipruritic effect, including benzodiazepines, muscle relaxants, opioid analgesics, tricyclic antidepressants and antiepileptic drugs, or ultraviolet B phototherapy in the past one week prior to participate in this trial or during the trial.
4. Concomitant elevation of liver enzymes (GOT: male \>37 U/L, female:\>31 U/L, GPT: male \>41 U/L, female:\>31U/L), alkaline phosphatase (ALP\>104U/L), bilirubin (T-bil\>1.2 mg/dL), serum phosphorus (\>7 mg/dl), serum parathyroid hormone (\>300 pg/ml).
5. Patients who have the history of allergy to pregabalin, any acute illness, liver cirrhosis, hepatic failure, decompensated heart failure, inability to give informed consent, or poor compliance.
6. Patients with uncontrolled psychiatric disease, active malignancy, and untreated hypothyroidism.
7. Female patients who are pregnant, are nursing, or want to become pregnant.

Answer: D