Cancer PainPhase 3NoDoubtNCT07682558
Efficacy of Non-opioid Drugs in Addition to Opioid Therapy for Cancer Pain Management
A Phase 3 study testing Metamizole and Ibuprofen in people with Cancer Pain and Cancer Palliative Care, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial summary
The investigators investigate the efficacy of non-opioid analgesics compared to placebo together with opioid therapy for cancer pain management. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer Pain, Cancer Palliative Care
- What is being tested?
- Metamizole and Ibuprofen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 318 participants
- Where
- 1 siteSwitzerland
- Study dates
- Oct 2026to Nov 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Inpatient setting (discharge possible, if patient returns for End of Study Visit)
- Diagnosis of metastatic or locally advanced cancer
- Cancer pain as defined by IASP (International Association for the Study of Pain)
- Cancer pain therapy with opioids indicated for pain management or start thereof at baseline (drug, dose, and route at treating physician's discretion)
- Average daily pain intensity ≥ 3 on NRS (Numeric Rating Scale)
- Ability to swallow oral medication
- Informed Consent as documented by signature
Who cannot join
- History of allergy or allergy-like symptoms (bronchospasm, urticaria or severe cutaneous adverse reactions (SCARs)) or hypersensitivity to dipyrone (or other pyrazolones or pyrazolidines) or ibuprofen (or other Non-steroidal anti-inflammatory drug incl. acetylsalicylic acid)
- Moderate to severe renal insufficiency (creatinine-eGFR (estimated Glomerular Filtration Rate) <45 ml/min)
- Severe heart failure (New York Heart Association class III-IV)
- Severe hepatic impairment (liver cirrhosis with ascites) or hepatic porphyria
- History of agranulocytosis induced by dipyrone (or other pyrazolones or pyrazolidines)
- Active gastric and/or duodenal ulcers or bleeding
Show all 20Show fewer
- History of recurrent gastric and/or duodenal ulcers or gastrointestinal bleeding (≥2 distinct episodes of proven ulceration or bleeding) or increased tendency to bleeding
- Third trimester of pregnancy
- Breastfeeding
- G6PD deficiency
- Inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
- Intrathecal or epidural opioids or local or regional anesthetic therapy
- Additional second opioid for co-analgesic effects or other reasons (e.g., methadone, buprenorphine)
- Initiation of therapy with transdermal therapeutic system (TTS) opioid <48 hours before start of IMP
- Use of non-opioids with long half-life (i.e., acemetacin, celecoxib, etodolac, etoricoxib, ketorolac, naproxen, piroxicam, tenoxicam)
- Pain unrelated to cancer (e.g. chronic non-cancer pain [CNCP], postoperative, particularly following coronary artery or cardiopulmonary bypass surgery)
- Inability to follow study procedures or adhere to protocol (e.g., due to language problems, psychological disorders, dementia)
- Inability to abstain from other non-opioids (apart from IMP (Investigational Medicinal Product)) during study participation
- Participation in any interventional study targeted at pain management
- Participant is a family member or employee of the investigator
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Ursina Wernli, PhD contact
Switzerland1 site
University Hospital Basel
Basel, 4031
Christopher Boehlke, Prof. Dr., +41 61 265 25 25, christopher.boehlke@unibas.ch
About this study
Official title: Efficacy of Non-opioid Drugs in Addition to Opioid Therapy for Cancer Pain Management: a Double-blind, Randomized, Three Arm, Placebo Controlled Trial Assessing the Key Non-opioids Dipyrone (Metamizole) and Ibuprofen
The investigators investigate the efficacy of non-opioid analgesics compared to placebo together with opioid therapy for cancer pain management.
Read the detailed description
Pain in cancer is common and can be very debilitating. Approximately half of all people with a tumor experience moderate to severe pain during the course of patient's cancer. Nevertheless, pain management is often difficult because there are not yet enough reliable studies for some medications, especially when used in addition to opioids.
Therefore, the NoDoubt study is investigating whether metamizole and/or ibuprofen - compared to a placebo - in addition to opioids provide better pain relief for cancer patients. The main goal is to reduce pain intensity. The study also examines whether the need for opioids can be reduced. The results could help to establish a clear and standardized practice for the treatment of cancer pain in the future, thus leading to improved care for cancer patients.
- Conditions
- Cancer Pain, Cancer Palliative Care
- Being tested
- Metamizole, Ibuprofen, Placebo
- Medical subject headings
- Cancer Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetamizoleDrug
Metamizole 4 g/d as: 2 capsules of 500 mg Metamizole each (1000 mg) taken 4 x daily orally.
IbuprofenDrug
Ibuprofen 1.2 g/d as: 2 capsules of 150 mg Ibuprofen each (300 mg) taken 4 x daily orally
PlaceboOther
Placebo 0 g/d as: 2 capsules containing inactive substance (mannitol) taken 4 x daily orally.
| Study group | Role | What they receive |
|---|---|---|
| Opioid + Metamizole | Experimental | Not described Receives: Drug: Metamizole |
| Opioid + Ibuprofen | Experimental | Not described Receives: Drug: Ibuprofen |
| Opioid + Placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in cancer pain
The primary outcome will help to determine whether adding metamizole (dipyrone) or ibuprofen to opioids is more effective than adding placebo in reducing average daily pain intensity (primary outcome) in cancer patients.
- Average of 5-day average daily patient reported pain assessed on days 3 to 7 by numeric rating scale (NRS); The NRS ranges from 0 ("no pain") to 10 ("pain as bad as the patient can imagine")
Measured: up to 5 days
Secondary outcomes (15)
Assessment of equivalence of metamizole and ibuprofen in analgesic potency regarding the pain intensity
Our main secondary outcome will help to investigate whether metamizole and ibuprofen demonstrate similar analgesic potency (are equivalent) regarding the pain intensity. For assessment of equivalence, Average of 5-day average daily patient reported pain assessed on days 3 to 7 by numeric rating scale will be used.
Measured: up to 5 days
Worst pain in the past 24 hours by NRS
This outcome will be assessed at baseline and daily from day 3 to 7 using item 3 of the BPI-SF (Brief Pain Inventory - Short Form). The NRS ranges from 0 ("no pain") to 10 ("pain as bad as the patient can imagine"). It will also be assessed at End of Study Visit (EOS).
Measured: up to 8 days
Least pain in the past 24 hours by NRS
This outcome will be assessed at baseline and daily from day 3 to 7 using item 4 of the BPI-SF. The NRS ranges from 0 ("no pain") to 10 ("pain as bad as the patient can imagine"). It will also be assessed at EOS.
Measured: up to 8 days
Daily differences in pain intensity measured by NRS
This outcome will be assessed daily from day 3 to day 7 to investigate efficacy over the course of time. The NRS ranges from 0 ("no pain") to 10 ("pain as bad as the patient can imagine")
Measured: up to 7 days
Patient's Individual Primary Goal (IPG) achieved
The IPG will be specified at baseline and whether it has been achieved or not will be assessed at EOS based on the specified IPG at baseline.
The IPG reflects variation between individuals' analgesic goals and further individualize symptom assessment by allowing each patient to specify a primary goal regarding the amelioration of the main issue as asked at baseline (i.e., patient's most important item from this list: average pain, pain interference with mood or activity, number or duration of pain episodes, worst pain, other).
Measured: 8 days
Personal Symptom Goal (PSG) achieved
The PSG will be specified at baseline (NRS 0-10) and whether it has been achieved or not will be assessed daily from day 3 to 7.
Patients are asked at baseline "At what level would you feel comfortable with this symptom?" to identify the maximal symptom intensity they would consider comfortable on the NRS ranging from 0 ("no pain") to 10 ("pain as bad as the patient can imagine").
Measured: up to 7 days
Time to pain control [in days]
- Time until minimal clinically important difference (MCID) of 1 is achieved
- Time until PSG is achieved
MCID and PSG achieved (Yes/No) will be assessed daily from day 3 to 7.
Measured: up to 7 days
Patient Global Impression of Pain Change (PGIC) by verbal rating scale (VRS)
A 7-option rating-of-change scale to assess participant-reported response to pain therapy using a VRS ("very much improved", "much improved", "minimally improved", "no change", "minimally worse", "much worse", or "very much worse").
Measured: day 8
≥30% reduction in daily average pain (Yes/No)
This outcome will be assessed based on the average of daily patient reported pain intensity by NRS at baseline (BL-pain) compared to the daily average pain on the last day of the intervention period (day 7).
Measured: up to 7 days
Burden through interference of pain with general activity by NRS
Will be assessed at baseline and daily from day 3 to 7 using item 9 A ("General activity") of the BPI-SF. The NRS ranges from 0 ("does not interfere") to 10 ("completely interferes"). Both outcomes will also be assessed at EOS.
Measured: up to 8 days
Burden through interference of pain with mood by NRS
Will be assessed at baseline and daily from day 3 to 7 using item 9 B ("Mood") of the BPI-SF. The NRS ranges from 0 ("does not interfere") to 10 ("completely interferes"). Both outcomes will also be assessed at EOS.
Measured: up to 8 days
Number of opioid rescue medications per day
The daily number of IROs (Immediate Release Opioids) will be assessed.
Measured: up to 8 days
Morphine Equivalent Daily Dose (MEDD) (in mg) calculated by compound, dose and application route of IROs (Immediate Release Opioid) and EROs (Extended-release Opioids)
Baseline MEDD and MEDD at EOS will be assessed. This outcome will be assessed daily between day 1 and 7.
MEDD is calculated by multiplying the daily dose of the prescribed opioid (if not already morphine) by a compound-specific, route of application-dependent conversion factor.
The opioid conversion ratios used to calculate MEDD are based on the literature and practical clinical considerations on equianalgesic dosing.
Measured: up to 7 days
Number of pain episodes
This outcome will be assessed at baseline, daily between day 3 and 7. It will also be assessed at EOS.
Measured: up to 8 days
Duration [in minutes] of pain episodes
This outcome will be assessed at baseline, daily between day 3 and 7. It will also be assessed at EOS.
Measured: up to 8 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2026
- Study startOct 2026 (estimated)
- Primary completionNov 2029 (estimated)
- Study completionNov 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cancer PainStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A multicenter, randomized, double-blind, placebo-controlled, three-armed superiority trial with a 1:1:1 allocation ratio.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 318 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Collaborators
- Swiss GO Trial Group, Swiss National Science Foundation
- Responsible party
- Sponsor
- Investigators
- Christopher Boehlke, Prof. Dr., Principal investigator, University Hospital, Basel, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07682558
- Sponsor's protocol ID
- 2026-00784; ex23gaertner
- Acronym
- NoDoubt
- Status last verified
- Aug 2026
- First submitted
- 26 Jun 2026
- Last updated
- 19 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Non-opioid Drugs in Addition to Opioid Therapy for Cancer Pain Management: a Double-blind, Randomized, Three Arm, Placebo Controlled Trial Assessing the Key Non-opioids Dipyrone (Metamizole) and Ibuprofen
- ClinicalTrials.gov ID
- NCT07682558
- Acronym / sponsor ID
- NoDoubt / 2026-00784; ex23gaertner
- Conditions
- Cancer Pain, Cancer Palliative Care
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 318 participants (estimated)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Collaborators
- Swiss GO Trial Group, Swiss National Science Foundation
- Study start
- Oct 2026 (estimated)
- Primary completion
- Nov 2029 (estimated)
- Study completion
- Nov 2029 (estimated)
- First posted
- 6 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators investigate the efficacy of non-opioid analgesics compared to placebo together with opioid therapy for cancer pain management.
Detailed description
Pain in cancer is common and can be very debilitating. Approximately half of all people with a tumor experience moderate to severe pain during the course of patient's cancer. Nevertheless, pain management is often difficult because there are not yet enough reliable studies for some medications, especially when used in addition to opioids.
Therefore, the NoDoubt study is investigating whether metamizole and/or ibuprofen - compared to a placebo - in addition to opioids provide better pain relief for cancer patients. The main goal is to reduce pain intensity. The study also examines whether the need for opioids can be reduced. The results could help to establish a clear and standardized practice for the treatment of cancer pain in the future, thus leading to improved care for cancer patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- A multicenter, randomized, double-blind, placebo-controlled, three-armed superiority trial with a 1:1:1 allocation ratio.
| Arm | Type | Receives |
|---|---|---|
| Opioid + Metamizole | Experimental | Drug: Metamizole |
| Opioid + Ibuprofen | Experimental | Drug: Ibuprofen |
| Opioid + Placebo | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Inpatient setting (discharge possible, if patient returns for End of Study Visit)
- Diagnosis of metastatic or locally advanced cancer
- Cancer pain as defined by IASP (International Association for the Study of Pain)
- Cancer pain therapy with opioids indicated for pain management or start thereof at baseline (drug, dose, and route at treating physician's discretion)
- Average daily pain intensity ≥ 3 on NRS (Numeric Rating Scale)
Key exclusion criteria (20 listed)
- History of allergy or allergy-like symptoms (bronchospasm, urticaria or severe cutaneous adverse reactions (SCARs)) or hypersensitivity to dipyrone (or other pyrazolones or pyrazolidines) or ibuprofen (or other Non-steroidal anti-inflammatory drug incl. acetylsalicylic acid)
- Moderate to severe renal insufficiency (creatinine-eGFR (estimated Glomerular Filtration Rate) <45 ml/min)
- Severe heart failure (New York Heart Association class III-IV)
- Severe hepatic impairment (liver cirrhosis with ascites) or hepatic porphyria
- History of agranulocytosis induced by dipyrone (or other pyrazolones or pyrazolidines)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetamizoleMetamizole 4 g/d as: 2 capsules of 500 mg Metamizole each (1000 mg) taken 4 x daily orally. | Drug | Opioid + Metamizole |
| IbuprofenIbuprofen 1.2 g/d as: 2 capsules of 150 mg Ibuprofen each (300 mg) taken 4 x daily orally | Drug | Opioid + Ibuprofen |
| PlaceboPlacebo 0 g/d as: 2 capsules containing inactive substance (mannitol) taken 4 x daily orally. | Other | Opioid + Placebo |
Primary outcome
Change in cancer pain
Time frame: up to 5 days
The primary outcome will help to determine whether adding metamizole (dipyrone) or ibuprofen to opioids is more effective than adding placebo in reducing average daily pain intensity (primary outcome) in cancer patients. - Average of 5-day average daily patient reported pain assessed on days 3 to 7 by numeric rating scale (NRS); The NRS ranges from 0 ("no pain") to 10 ("pain as bad as the patient can imagine")
15 secondary outcomes
Assessment of equivalence of metamizole and ibuprofen in analgesic potency regarding the pain intensity
Time frame: up to 5 days
Worst pain in the past 24 hours by NRS
Time frame: up to 8 days
Least pain in the past 24 hours by NRS
Time frame: up to 8 days
Daily differences in pain intensity measured by NRS
Time frame: up to 7 days
Patient's Individual Primary Goal (IPG) achieved
Time frame: 8 days
Personal Symptom Goal (PSG) achieved
Time frame: up to 7 days
Time to pain control [in days]
Time frame: up to 7 days
Patient Global Impression of Pain Change (PGIC) by verbal rating scale (VRS)
Time frame: day 8
≥30% reduction in daily average pain (Yes/No)
Time frame: up to 7 days
Burden through interference of pain with general activity by NRS
Time frame: up to 8 days
Burden through interference of pain with mood by NRS
Time frame: up to 8 days
Number of opioid rescue medications per day
Time frame: up to 8 days
Morphine Equivalent Daily Dose (MEDD) (in mg) calculated by compound, dose and application route of IROs (Immediate Release Opioid) and EROs (Extended-release Opioids)
Time frame: up to 7 days
Number of pain episodes
Time frame: up to 8 days
Duration [in minutes] of pain episodes
Time frame: up to 8 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ursina Wernli, PhD contact
Christopher Boehlke, Prof. Dr. principal investigator
University Hospital, Basel, Switzerland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Metamizole and Ibuprofen in people with Cancer Pain and Cancer Palliative Care, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 19 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Christopher Boehlke, Prof. Dr. (+41 61 265 25 25,, christopher.boehlke@unibas.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in cancer pain (time frame: up to 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2026.