PARASTOP - Paracetamol with Strong Opioids

2024-515012-53-00 Protocol PARASTOP Therapeutic confirmatory (Phase III) Ended

Start 20 Oct 2021 · End 18 Feb 2026 · Status Ended · 1 EU/EEA countries · 12 sites · Protocol PARASTOP

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ended
Participants planned 204
Countries 1
Sites 12

Metastatic cancer disease

The main objective is to investigate whether withdrawal of paracetamol when used together with strong opioids provides inferior pain control compared to continuous use of paracetamol together with strong opioids.

Key facts

Sponsor
Oslo University Hospital HF
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Neoplasms [C04]
Trial duration
20 Oct 2021 → 18 Feb 2026
Decision date (initial)
2024-10-29
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No

External identifiers

EU CT number
2024-515012-53-00
EudraCT number
2020-005123-36
ClinicalTrials.gov
NCT05051735

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Therapy

The main objective is to investigate whether withdrawal of paracetamol when used together with strong opioids provides inferior pain control compared to continuous use of paracetamol together with strong opioids.

Secondary objectives 3

  1. Does placebo compared to paracetamol in cancer pain patients already on strong opioids result in more opioid-related side effects?
  2. Does paracetamol withdrawal in cancer pain patients already on strong opioids influence patient's global impression of change?
  3. Does placebo compared to paracetamol in patients with cancer-related pain already on strong opioids change patients' opioid consumption?

Conditions and MedDRA coding

Metastatic cancer disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

  1. Participant must be ≥ 18 years of age inclusive, at the time of signing the informed consent.
  2. Participant must be ≥ 18 years of age inclusive, at the time of signing the informed consent.
  3. Participants who are under palliative care or oncology service review
  4. Diagnosis of metastatic cancer. This includes all incurable solid malignancy in an advanced stage, either locally advanced or metastatic. This also includes malignant lymphoma in the palliative setting and multiple myeloma with bone disease.
  5. Clinician-predicted life expectancy >2 months
  6. Receiving daily regular strong opioids for cancer pain
  7. Receiving stable scheduled opioid dose last 48 hours
  8. Receiving paracetamol 1 gram x three or four times a day for at least five days
  9. Average pain intensity past 24 hours ≥ 2 and ≤ 7 (NRS 0-10)
  10. Able to take study drug/placebo as tablets
  11. Able to take study drug/placebo as tablets
  12. Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol

Exclusion criteria 7

  1. History of allergy or hypersensitivity to any of the active substances or excipients in the study drug
  2. Known severe liver or renal failure equivalent with CTCAE Grade 3 or 4* precluding continuation of paracetamol. (*Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0)
  3. Participants receiving subcutaneous, intravenous, intrathecal, or epidural opioid therapy
  4. Participants receiving systemic anticancer treatment during the intervention period if they are anticipated to have increasing pain or other symptoms related to the treatment
  5. Co-enrolment in other drug trials. Participants will not be enrolled in any other ongoing interventional clinical trial. Study participants may be enrolled in noninterventional research (e.g. questionnaire, tissue collection studies)
  6. Previously enrolled in this study
  7. Pregnant or lactating women

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Average pain intensity

Secondary endpoints 3

  1. Patient reported opioid related side effects
  2. Patient reported opioid related side effects
  3. Opioid consumption Day 8 (Total amount of scheduled and on demand opioids)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Paracet 1 g tabletter

PRD345336 · Product

Active substance
Paracetamol
Substance synonyms
ACETAMINOPHEN
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
4 g gram(s)
Max total dose
28 g gram(s)
Max treatment duration
7 Day(s)
Authorisation status
Authorised
ATC code
N02BE01 — PARACETAMOL
Marketing authorisation
01-9312
MA holder
KARO PHARMA AS
MA country
Norway
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
Marketed product has been milled, and then compressed to new tablets (500 mg)

Placebo 1

Placebo

SUB21402 · Substance

Active substance
Placebo
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
4 g gram(s)
Max total dose
28 g gram(s)
Max treatment duration
7 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oslo University Hospital HF

73 Total trials 37 Recruiting 25 Ended
Academic / Non-commercial
Sponsor organisation
Oslo University Hospital HF
Address
Taarnbygget, Kirkeveien 166 Kirkeveien 166
City
Oslo
Postcode
0450
Country
Norway

Scientific contact point

Organisation
Oslo University Hospital HF
Contact name
Stein Kaasa

Public contact point

Organisation
Oslo University Hospital HF
Contact name
Ørnulf Paulsen

Locations

1 EU/EEA country · 12 investigational sites

By country

CountryMS statusPlanned subjectsSites
Norway Ended 179 12
Rest of world
Uganda
 — 25 —

Investigational sites

Norway

12 sites · Ended
Vestre Viken HF
Palliative Care Unit, Dronninggata 28, 3004, Drammen
Oslo University Hospital HF
Seksjon for lindrende behandling, Taarnbygget, Kirkeveien 166, Oslo
Helse Stavanger HF
Palliativt senter, Gerd-Ragna Bloch Thorsens Gate 8, 4011, Stavanger
Akershus University Hospital
Palliativ avdeling, Sykehusveien 27, 1478, Lorenskog
St. Olavs Hospital HF
Avdeling Palliasjon, Prinsesse Kristinas G. 3, 7030, Trondheim
Sykehuset I Vestfold HF
Cancer center, Halfdan Wilhelmsens Alle 17, 3116, Toensberg
Helse Moere Og Romsdal HF
Klinikk for kreftbehandling, Aasehaugen 1, 6017, Aalesund
Sorlandet Sykehus HF
Senter for kreftbehandling, Egsveien 100, 4615, Kristiansand S
Helse Forde HF
Palliativt team, Svanehaugvegen 2, 6812, Foerde
Universitetssykehuset Nord-Norge HF
Kreftavdelingen, P. O. Box 100, 9038, Tromsoe
Sykehuset Oestfold HF Kalnes
Senter for lindrende behandling, Kalnesveien 300, 1714, Graalum
Sykehuset Telemark HF
Medisinsk klinikk, Ulefossvegen 55, 3710, Skien

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Norway 2021-10-20 2026-02-18 2021-10-20 2026-02-04

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol 2024-515012-53-00_Redacted 5.3
Protocol (for publication) D4_Patient facing documents EORTC QLQ-C15 PAL 3.0
Protocol (for publication) D4_Patient facing documents Opioid side effects questionnaire 1
Protocol (for publication) D4_Patient facing documents Pain intensity past 24 hours questionnaire 1
Protocol (for publication) D4_Patient facing documents PGIC questionnaire 1.0
Recruitment arrangements (for publication) K1_Recruitment arrangements 1
Recruitment arrangements (for publication) K2_Recruitment material Poster 1
Recruitment arrangements (for publication) Placeholder minimum 001 1
Subject information and informed consent form (for publication) L1_SIS and ICF Adults 4.1
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC Paracetamol 1
Synopsis of the protocol (for publication) D1_Protocol Synopsis NO EU CT 2024-515012-53-00 1

Application history

2 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-10-08 Norway Acceptable
2024-10-24
 2024-10-29
2 SUBSTANTIAL MODIFICATION SM-1 2025-04-01 Norway Acceptable
2025-05-09
 2025-05-19

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